254 J Contemp Med Sci | Vol. 5, No. 5, September-October 2019: 254–257 Premalignant changes associated chronic gastritis in Karbala Province: multi institutional study Rasha Abd Alraouf Neama AlSafi, Mohammed F. Alqanbar, and Wafaa Redha Mohammed Al-Sabbagh Department of Pathology, College of Medicine, Karbala University, Karbala, Iraq. Correspondence to Rasha Abd Alraouf Neama AlSafi (email: rasha.alsafi78@gmail.com). (Submitted: 26 April 2019 – Revised version received: 18 May 2019 – Accepted: 13 July 2019 – Published online: 26 October 2019) Introduction The incidence rate of gastric cancer has been decreased gradu- ally and continuously over the last years; however it ranks as the fourth most prevalent cancer and a significant leader to cancer related death over the world.1,2 Cancer of the stomach from histopathological aspect is of two types, the intestinal and the diffuse types. The occurrence of the intestinal type may be preceded by a series of precancerous pathological lesions and changes such as chronic atrophic gastritis, intes- tinal metaplasia (IM), and dysplasia.3 However, the genesis of the diffuse type is not clearly recognized.4 Helicobacter pylori infection is accompanied with a sequen- tial events such as severe gastritis, chronic atrophic gastritis, IM and gastric cancer.5,6 intensely atrophied gastric mucosa that associated with intestinal metaplastic changes may be attributed to infection with certain types of high risk H. pylori.7,8 It was noticed that the infection with H. pylori during early childhood resulted in premalignant state of pan-gastritis in adulthood. So, the infection with H. pylori earlier during life is considered as an important risk factor that increase the opportunity for the evo- lution of gastric cancer.9,10 Other risk factors of IM are high salt consumption, cigarette smoking, alcohol drinking, and chronic bile reflux.11 The prevalence of H. pylori infection has been recorded from multiple Middle Eastern countries such as Iraq, Iran, Turkey, Libya, Egypt, Bahrain, Oman, Saudi Arabia, and the United Arab Emirates. It has been found that the rate of infection with H. pylori are nearly similar in these countries but still there is little variations in that the prevalence of infection reach its peak in Iran while it is nearly uncommon and rare in Iraq and Egypt.12 According to a study conducted at 2009 in Iraq stated that the “The mild pathology and antral-predominant gastritis may help to explain the low cancer rate in Iraq”.13 The aim of this study was to investigate the prevalence of gastric premalignant changes like gastric atrophy, intestinal metaplasia and dysplastic changes that associated with chronic gastritis and their relation with H. pylori infection in different age groups in patients underwent esophagogastroduodenos- copy in three health institutions in Karbala province. Materials and Methods The data was collected from patients attended the endoscopy units during a period from January to September 2018 in three medical centers in holy Karbala, Iraq, Al Hussein Teaching Hospital, Imam Zain Al Abedin Hospital and Imam AL Hujjah Hospital. It includes 500 patients who were subjected to esoph- agogastroduodenoscopy (EGD) in this period from whom endoscopic mucosal biopsies were taken. Each biopsy con- tained at least two mucosal pieces that submitted to a conven- tional histological processing and stained with hematoxylin–eosin stain to assess the presence of gastric mucosal changes. These biopsies were stained by Giemsa to detect H. pylori organisms. The collected data include many parameters such as age, sex, and histopathological findings (gastritis, H. pylori infection, atrophic changes, intestinal metaplasia and dysplastic changes). Informed written consent was taken from each patient before the inclusion. Inclusion Criteria All patients who attended hospitals with upper GIT symptoms and underwent EGD with gastric mucosal sampling during the period of the study. Objectives The aim of this study was to investigate the prevalence of gastric premalignant changes as gastric atrophy, intestinal metaplasia and dysplastic changes in patients underwent esophagogastroduodenoscopy in three health institutions in Karbala province. Methods The data was collected from patients attended the endoscopy units during a period from January to September 2018 in three medical centers in holy Karbala, Iraq, Al Hussein Teaching Hospital, Imam Zain Al Abedin Hospital and Imam AL Hujjah Hospital. It includes 215 males and 285 females who were subjected to esophagogastroduodenoscopy (EGD) from whom mucosal biopsies were taken. These biopsies were stained by Giemsa to detect Helicobacter pylori organisms. Results The mean age of patients was (40.9 ± 15 years SD). Helicobacter pylori infection was demonstrated in (71%) patients, (19.4%) were presented with glandular atrophy, (7.4%) out of 500 patients had intestinal metaplasia and only six (1.2%) patients had dysplastic changes. there was a significant statistical relation between gastric glandular atrophy and age (P-value = 0.03). There was a significant statistical relation between glandular atrophy and infection with H. pylori (P-value = 0.001). There was a significant negative relation between H. pylori infection and the existence of intestinal metaplasia (P-value = 0.0001). This study show a significant statistical relationship between the existence of intestinal metaplasia and the occurrence of dysplastic changes (P-value = 0.001). Conclusion The current study show a significant relation between aging and the existence of gastric glandular atrophy. There was a significant relation between each of gastric glandular atrophy and intestinal metaplastic changes with the H. pylori infection. There was a significant relation between gastric intestinal metaplasia and dysplastic changes. Keywords premalignant changes, age, H. pylori, gastric atrophy, intestinal metaplasia, dysplasia ISSN 2413-0516 Original 255J Contemp Med Sci | Vol. 5, No. 5, September-October 2019: 254–257 R.A.A.N. AlSafi et al. Premalignant changes associated chronic gastritis in Karbala Province Exclusion Criteria This include patients diagnosed to have gastric cancer, those patients undergoing gastric surgery, patients with upper gas- trointestinal bleeding and patients with lacking data. Statistical Analysis Chi-square test was used to measure the association between different parameters and P-value of <0.05 was considered significant. Results Five hundred patients were subjected to EGD, enrolled in this study during a period from January to September 2018. The mean age of patients was (40.9 ± 15 years standard deviation). There were 215 (43%) males and 285 (57%) females. All patients have gastritis [500 (100%)]. H. pylori infection was demonstrated in 355 (71%) patients. Out of 500 patients, 97 (19.4%) were presented with glan- dular atrophy, 37 (7.4%) out of total number of patients had intestinal metaplasia, while only six (1.2%) patients had dys- plastic changes distributed equally between males and females. The results of this study show that the highest frequencies of patients infected with H. pylori were distributed between 20 and 59 years of age; however, this relation was not significant statistically (P-value = 0.06). There was a significant statistical relation between gastric glandular atrophy and age in that the number of cases with atrophied gastric glands was growing with increasing the age from 20 to 60 years forming about 76 (78.3%) cases (P-value = 0.03). Concerning intestinal metaplasia, the results revealed a mounting rate of metaplastic changes with the age and the rela- tionship was statistically near the significant level (P-value = 0.052). All cases with dysplasia were six (1.2%) distributed unevenly through age groups from 30 to 69 years, the relation- ship of these changes with age was statistically insignificant (P-value = 0.7). The distribution and the relationship of the histopatho- logical findings (H. pylori infection, gastric glandular atrophy, intestinal metaplasia and dysplastic changes) with age was demonstrated in Table 1. Of 355 patients infected with H. pylori, there were 88 (24.8%) cases presented with glandular atrophy in comparison to only 9/145 (6.2%) of non-infected patients who presented with atrophied gastric glands and this figure reach a significant level statistically (P-value = 0.001). Additionally there is a sta- tistical significant negative relationship between intestinal metaplastic changes and the existence of H. pylori infection in that 17 patients (4.8%) with H. pylori infection were presented with intestinal metaplasia in comparison to 20 (13.8%) of non-infected patients presented with intestinal metaplasia on examination as shown in Table 2. Out of total 37 cases which show intestinal metaplasia there were three (8.1%) cases which were diagnosed to have dysplastic changes while three (0.7%) cases out of the remaining negative cases show dysplastic changes. This result give a significant statistical relationship between the existence of intestinal metaplasia and the occurrence of dysplastic changes (P-value = 0.001) as shown in Table 3. Discussion In the model of gastric carcinogenesis, H. pylori has a substan- tial effect in the development of chronic active gastritis. Table 1. The histopathological findings of 500 patients underwent esophagogastroduodenoscopy and their relations with age Histopathological findings (frequency) Frequencies (%) Age groups (years) P-value 10–19 20–29 30–39 40–49 50–59 60–69 70–79 ≥80 H. pylori - Positive 355 (71)* 29 75 87 73 45 33 13 0 (0.06) - Negative 145 (29)* 5 24 35 34 28 11 6 2 Glandular atrophy - Positive 97 (19.4)* 9 15 19 20 22 5 7 0 (0.03) - Negative 403 (80.6)* 25 84 103 87 51 39 12 2 Intestinal-metaplasia - Positive 37 (7.4)* 0 4 10 7 9 5 1 1 (0.052) - Negative 463 (92.6)* 34 95 112 100 64 39 18 1 Dysplastic changes - Positive 6 (1.2)* 0 0 2 1 2 1 0 0 (0.7) - Negative 494 (98.8)* 34 99 120 106 71 43 19 2 *Percentage from total sample size (500). Table 2. The relation of H. pylori infection with glandular atrophy and intestinal metaplasia H. pylori infection Atrophy (P-value = 0.001) Intestinal metaplasia (P-value = 0.0001) Total Positive (%) Negative (%) Positive (%) Negative (%) Positive 88 (24.8)* 267 (75.2)* 17 (4.8)* 338 (95.2) 355 Negative 9 (6.2)** 136 (93.8)** 20 (13.8)** 125 (86.2) 145 *Percentage out of total positive cases infected with H. pylori. **Percentage out of total cases not infected with H. pylori. Original 256 J Contemp Med Sci | Vol. 5, No. 5, September-October 2019: 254–257 Premalignant changes associated chronic gastritis in Karbala Province R.A.A.N. AlSafi et al. Chronic H. pylori infection may pave the way to pass through sequential stages of atrophic gastritis, IM, and dysplasia to end with gastric adenocarcinoma.14 In this study (according to Table 1), H. pylori infection was demonstrated in 355 (71%) patients and this come in con- gruent with previous study which give a similar figures.15 Other studies reported in the prevalence in North Europe and North America was <40%, while it was over 70% in East Asia, Africa, and Middle East region.16,17 which comes in consist- ency with the results of this study while it is far from the figure detected in a Turkish study which found H. pylori positivity to be 82%.18 The differences in the reported figures may be related to the point that the incidence actually varies according to living environment, occupation, and geographic region in addition to the diversity in the detection methods. In the current study, 97 (19.4%) patients were presented with glandular atrophy; the prevalence is different from another Iraqi study done in Dohuk, with smaller sample size which record glandular atrophy in just 3% of gastric biopsies13 and may be more sim- ilar to a study conducted in Al-Kuwait, in which 28.3% of patients had atrophic gastritis while the prevalence still high and were 65% and 54% of examined Jordanian and Egyptian patients respectively.19–21 In a Turkish study, the atrophy was found in 75% of the subjects22 the differences in the results may be attributed to the differences in samples size that affect the results or due to subjectivity between pathologists in making the diagnosis of glandular atrophy. In this study, 37 (7.4%) out of total number of patients had intestinal meta- plasia, this figure was similar to that detected in two other studies in United States and Netherlands in which the preva- lence of intestinal metaplasia were 7% and 8% respectively.23,24 Almouradi et al.25 reported that, among the 437 patients who had gastric biopsies performed, 66 were found to have gastric IM and they observed that the overall prevalence was 15%. Additional Turkish study reporting a prevalence of intestinal metaplasia of 13.8%.3 The commonness of gastric intestinal metaplasia publi- cally is still hardly to be ascertain because of the symptomless character of this lesion. There is a wide variation in the preva- lence of gastric IM between these studies may be related to the variability in localization and sampling of focal metaplastic lesions.3 From 500 cases only six (1.2%) patients had dysplastic changes. A compatible result was detected by a Turkish study in which dysplastic changes was 2%18 while it differ from that recorded by Iranian study in which the dysplastic changes may reach up to 71% and higher.26 According to the results of this study, there is a significant relationship between the age and glandular atrophy but there was no such a relation with other factors like H. pylori infection, intestinal metaplasia and dysplastic changes. This result come in consistency with other study which find that subjects with glandular atrophy were significantly older27 while it differs from other Turkish studies which show that intestinal metaplasia and H. pylori infection is detected in elderly subjects.18,28 This could be attributed to environmental and dietary habits that predispose to early H. pylori infection and its consequences, making them unrelated to the age as an influ- encing factor, while still glandular atrophy considered part of general degenerative process rather than related to H. pylori infection. In this study (according to Table 2), there were 24.8% cases which were diagnosed to have H. pylori infection were presented with glandular atrophy. In two different Turkish studies, histopathological examination reveal that the mucosal atrophy was found in 43–75% of H. pylori infected subjects,22,29 In Iran, in a study, the atrophied gastric mucosal epithelium was seen in 22% of gastric biopsies.26 In Al Kuwait, 28.3% of H. pylori infected patients were had atrophic gastritis.19 Gastric atrophy was observed in 65% and 54% of examined patients in Jordan and Egypt, respectively.20,21 Again this could be attrib- uted to subjective criteria in determination of gastric atrophy as well as difference in the sample size and ethnicity. The cur- rent study show that there is a significant negative relationship between H. pylori infection and gastric intestinal metaplasia in that 4.8% of patients presented with H. pylori infection were diagnosed to have intestinal metaplastic changes in compar- ison to 13.8% of cases without H. pylori infection show intes- tinal metaplasia on examination. This figure is similar to that recorded by other studies.8,25,30 Intestinal metaplasia may cause lower diagnostic accu- racy of H. pylori with histologic examination.11 As clearly known, H. pylori selectively lives in gastric mucosa. Hence, the impairment of H. pylori colonization in the areas with intes- tinal metaplasia is predictable.16 At the same time, although the gastric mucosa with intestinal metaplasia looks like the intestinal mucosa, it would still have the features of gastric mucosa according to the grade of metaplasia.18 According to the results of this study (Table 3), there was a significant statistical relationship between the existence of intestinal metaplasia and the occurrence of dysplastic changes. This result may be harmonized with many recent studies.31–33 Conclusion The current study provides information about the prevalence of H. pylori infection in patients underwent EGDs in three main institutions in Karbalaa province was 71%. The preva- lence of intestinal metaplasia is a premalignant changes recording an alarming figure among patients with chronic gastritis. It was noticed that prevalence of gastric glandular atrophy was increased gradually with age with no such relation with intestinal metaplasia and dysplastic changes as premalignant changes occur in younger age groups. The absence of signifi- cant relation between age and IM could be considered as alarming feature that these changes could be occur earlier in our population. Conflicts of Interest None.  Table 3. The association between intestinal metaplasia and dysplastic changes Metaplasia Dysplasia Total P-value Negative (%) Positive (%) Negative 460 (99.3)* 3 (0.7)* 463 0.001 Positive 34 (91.9)** 3 (8.1)** 37 Total 494 6 500 *The percentage is out of total negative cases. **The percentage is out of total positive cases. Original 257J Contemp Med Sci | Vol. 5, No. 5, September-October 2019: 254–257 R.A.A.N. AlSafi et al. 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