Helicobacter pylori">

International Journal of Applied and Basic Medical Research

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 6  |  Issue : 1  |  Page : 18--22

The diagnostic accuracy of rapid urease biopsy test compared to histopathology in implementing "test and treat" policy for Helicobacter pylori


Asitava Deb Roy1, Swapna Deuri2, Umesh Chandra Dutta2,  
1 Department of Pathology, IQ City Medical College, Durgapur, West Bengal, India
2 Department of Pathology, Gauhati Medical College, Guwahati, Assam, India

Correspondence Address:
Asitava Deb Roy
Department of Pathology, IQ City Medical College, Sovapur, Bijra Road, Jaymua, Durgapur - 713 206, West Bengal
India

Abstract

Background: Helicobacter pylori is one of the most important causes of the varied spectrum of gastroduodenal diseases. It is important to have a rapid diagnostic method to detect the organism so as to initiate the treatment early and check its progression to malignancy. Aims: To evaluate the diagnostic accuracy of rapid urease biopsy test in detecting H. pylori infection and implementation of DQtest and treatDQ policy. Materials and Methods: All patients of chronic dyspepsia not responding to conventional treatment were subjected to endoscopy, and mucosal biopsy samples were collected. A rapid urease test (RUT) and histopathology was performed on these samples and taking histopathology as gold standard for H. pylori demonstration, the diagnostic accuracy of RUT was evaluated. Results: The specificity, sensitivity, positive predictive value, negative predictive value, and diagnostic accuracy of RUT were 97.22%, 94.04%, 98.75%, 87.5%, and 95%, respectively. Conclusion: Use of a rapid diagnostic test viz., rapid urease biopsy test to confirm H. pylori infection is recommended for early diagnosis and treatment of H. pylori associated gastroduodenal diseases.



How to cite this article:
Roy AD, Deuri S, Dutta UC. The diagnostic accuracy of rapid urease biopsy test compared to histopathology in implementing "test and treat" policy for Helicobacter pylori.Int J App Basic Med Res 2016;6:18-22


How to cite this URL:
Roy AD, Deuri S, Dutta UC. The diagnostic accuracy of rapid urease biopsy test compared to histopathology in implementing "test and treat" policy for Helicobacter pylori. Int J App Basic Med Res [serial online] 2016 [cited 2022 Jan 25 ];6:18-22
Available from: https://www.ijabmr.org/text.asp?2016/6/1/18/174003


Full Text

 Introduction



The spectrum of gastroduodenal diseases is wide ranging from inflammatory lesions such as gastritis and peptic ulcer disease to frankly malignant ones such as gastric carcinoma and lymphoma. Of the diverse etiological associations of gastroduodenal disease, the most important is a bacterium named Helicobacter pylori.[1] Chronic infection of the gastric mucosa by this bacterium is the most common infection worldwide. [2]

Chronic gastritis, if left untreated, may progress to carcinoma. [1] Hence, whenever possible, it is necessary to identify the cause of gastritis to check the progression to carcinoma. [1] H. pylori being one such cause of chronic gastritis, rapid diagnosis with the help of chemical tests (rapid urease test [RUT]) is essential to formulate early and appropriate clinical strategies for better management of patients.

The "test and treat" policy is the recommended way to eradicate H. pylori in patients with uninvestigated dyspepsia if the prevalence of H. pylori is high. [3] India is considered to have a high prevalence of H. pylori. [3] This observational study was conducted to discover the prevalence of H. pylori disease in uninvestigated dyspeptic patients based on rapid urease biopsy test and to ascertain the role of this test in implementing the "test and treat" policy in this geographical area.

 Materials and Methods



The study was conducted in the Department of Pathology and Gastroenterology over a period of 1-year. Patients more than 18 years of age, having clinical indications of upper gastrointestinal endoscopy, and patients not under treatment with proton pump inhibitors, bismuth compounds, antibiotics in the last 3 weeks, and H 2 blockers in the last 24 h were included in the study. Patients with esophageal disease, patients who have been previously treated with anti-H. pylori drug regime, patients who had ultrasonographic evidence of pancreatitis, biliary disease, or chronic liver disease, and patients with abnormal coagulation profile were excluded from the study. An informed consent and a thorough clinical history were taken from all the patients who were selected for the study. Routine blood and stool examinations were done. An ultrasonography (whole abdomen) was done to rule out pancreatic and biliary tract disease.

After an overnight fast (6 h), all the selected subjects underwent upper gastrointestinal endoscopy with flexible fiber-optic endoscope (Fujinon© ) and the endoscopic findings were noted. In cases, which were endoscopically normal or only with erosions, mucosal biopsies were taken with sterile biopsy forceps (Olympus©© ) from four different sites: Cardia (greater curvature), antrum (greater curvature), incisura angularis (lesser curvature), and first part of duodenum. This was in accordance with the recommendations of Genta and Graham. [4] In cases with the presence of an ulcer (clinically benign) anywhere in the stomach or first part of duodenum, additional multiple bits of tissue were taken from the different edges of the lesion (over and above the four sites mentioned) for histopathological examination. In cases with the presence of a growth (clinically malignant) only, multiple bits of tissue from different edges of the growth were taken.

An additional mucosal biopsy was taken from the antrum for the RUT for H. pylori in all cases. In cases, where the antrum was involved with erosions/ulcer/growth, the biopsy was taken from surrounding normal mucosa for RUT. In this study, Pylotest TM kit manufactured and marketed by Halifax Research Laboratories, Kolkata was used for biopsy urease test [Figure 1]. Fresh mucosal biopsy samples from antrum were obtained with biopsy forceps and put in the urea gel media with the help of a needle and crushed. The results are usually obtained by 6-9 h but can be interpreted up to 24 h. [5] In this study, however, the positive results were obtained within 6-9 h, in majority of the cases. A known urease positive culture colony (Klebsiella) was taken as a control for the test. All the mucosal biopsy samples obtained for histopathology were put in different bottles containing 10% formalin and properly labeled mentioning the site of biopsy. These tissue samples were routinely processed and stained with hematoxylin and eosin (H and E) for light microscopic examination. In some cases, a modified Giemsa stain was performed to demonstrate H. pylori in the tissue sections. [6]{Figure 1}

Cases were considered to be H. pylori infected when both RUT and histology were positive. All the cases of chronic gastritis were reported following the guidelines put forward by the updated Sydney system of reporting, [7] with an additional note on the pathological involvement of the first part of duodenum. The malignant cases were diagnosed and classified according to the guidelines put forward by World Health Organization (WHO). [8]

 Results



It was seen that maximum patients (31 out of 120, i.e., 25.83%) were in the age group of 38-47 years with a slight male preponderance (M: F = 1.2:1). The most common presenting symptom was upper abdominal pain (106 out of 120 cases, i.e., 88.3%) and the most common finding on endoscopy was ulcerative growth at the antrum (26 out of 120 i.e., 21.66%) followed by duodenal ulcer (25 out of 120 i.e., 20.83%) [Table 1].{Table 1}

It was observed that of all the 120 patients who underwent upper gastrointestinal endoscopy, 79 cases (65.83%) were positive for H. pylori infection. Results also showed that 24 out of 25 (96%) cases of duodenal ulcers, 13 out of 21 (61.9%) cases of gastric ulcers, and 13 out of 26 (50%) cases of ulcerative growth were positive for H. pylori [Table 2].{Table 2}

Taking histological demonstration of H. pylori as standard the definitions were derived and data were obtained as: True positive = H. pylori detected by both histopathology and RUT = 79; true negative = H. pylori not detected by any of the two methods = 35; false positive = H. pylori detected by RUT but not by histopathology = 1; and false negative = H. pylori not detected by rapid urease but detected by histopathology = 5. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of RUT were 97.22%, 94.04%, 98.75%, 87.5%, and 95%, respectively.

On histopathological examination of all the 120 cases, 85 (70.83%) cases turned out to be inflammatory, 6 cases (5%) dysplastic, and 27 cases (22.49%) neoplastic (1 benign and rest 26 malignant). Two cases (1.66%) had no histopathological abnormality.

Of the 85 inflammatory lesions, most common diagnosis was chronic gastritis (in 29 cases i.e., 33.72%) followed by chronic gastritis with duodenitis (in 27 cases i.e., 31.39%) [Table 3].{Table 3}

Of the 6 dysplastic lesions, 4 (66.67%) were low-grade, and 2 (33.33%) were high-grade. Of the neoplastic cases, 1 was benign hyperplastic polyp, 25 were gastric adenocarcinoma, and 1 duodenal adenocarcinoma.

On classifying all the 25 cases of gastric adenocarcinoma on the basis of WHO guidelines (2000), 14 (56%) were tubular adenocarcinoma, 9 (36%) were diffuse, and 1 (4%) each of papillary and mucinous adenocarcinoma. The only case of duodenal adenocarcinoma was moderately differentiated. While evaluating for the presence of H. pylori infection on histopathology, it was found that 18 out of 29 (62.06%) cases of chronic gastritis were associated with H. pylori infection. An important observation in our study was that all cases of chronic atrophic gastritis were positive for H. pylori infection [Table 4].{Table 4}

Three out of 4 (75%) cases of low-grade and 1 out of 2 (50%) cases of high-grade dysplasia were positive for H. pylori. Thirteen out of 26 (50%) cases of adenocarcinoma were positive for H. pylori infection. Among the cases of gastric adenocarcinoma, 9 out of 14 (64.28%) cases of tubular adenocarcinoma, and 4 out of 9 (44.44%) cases of diffuse adenocarcinoma were positive for H. pylori [Table 5]. [Figure 2] shows the distribution of the malignant cases based on WHO (2000) guidelines.{Figure 2}{Table 5}

 Discussion



H. pylori , as a cause of chronic gastritis, has always been a cause of concern for the treating physicians. Ghosal et al.[9] and Ahmed et al.[10] in their studies from India showed that the prevalence of H. pylori infection in adults approaches 90% in many developing countries, particularly those in the tropics. In 2007, Lynn et al.[11] and Sacco et al.[12] in their province based individual studies, have shown that in industrialized parts of the world (Western Europe, United States, Canada, and Australia), exposure tends to occur later in life, which results in a lower percentage of infected adults. In eastern Asia (e.g. Japan), where there has been a recent introduction of improved sanitation methods, there has been a clear trend toward a lower rate of H. pylori infection. [13]

Chen et al.[14] showed that the prevalence of H. pylori infection has been steadily declining in industrialized and emerging countries, which is probably a reflection of improved sanitary conditions, as well as widespread use of antibiotics. Despite declining rates of H. pylori infection, in general, the prevalence rate of H. pylori in patients who undergo endoscopy remains significant. Therefore, H. pylori should be considered in all gastric biopsy specimens examined, regardless of the patient's age or provenance. [2]

The diagnosis of H. pylori gastritis based solely on the endoscopic gross appearance of the gastric mucosa is not recommended. The accurate diagnosis of H. pylori gastritis rests either on the pathologic evaluation of gastric mucosal biopsies or by detection of urease in mucosal specimens by rapid urease biopsy test. H. pylori are curved or S-shaped bacilli and in this form are often easily recognized on routine H and E staining [Figure 3]. They are found within the surface mucus layer [Figure 4] and are easiest to identify within gastric pits, but in cases of heavy infection are also numerous overlying the surface epithelium. Special stains are necessary when screening biopsies for H. pylori as they facilitate recognition, especially when small numbers are present, and help distinguish the bacteria from fibrin or debris on the mucosal surface. A variety of stains has been used. A study by Rotimi et al. found that modified Giemsa is the method of choice because it is cheap, sensitive, and easy to perform and reproducible. [15] This is very satisfactory for routine use. Monteiro et al. found the sensitivity, specificity, PPV, and NPV of histologic examinations by Giemsa stain is 93.8%, 98.2%, 97.9%, and 94.8%, respectively. [16]{Figure 3}{Figure 4}

First described by Mc Nulty and Wise in 1985, the rapid urease breath test has gained wide acceptance in the detection of H. pylori in mucosal biopsy samples. [17] Several studies [16],[18],[19],[20] have found the sensitivity of this test between 80% and 99% and specificity between 92% and 100% taking histopathology as the gold standard for the detection of this bacillus. The overall sensitivities were 88-94% and specificities 99-100% in all the studies, including the present one [Table 6]. This shows that a positive RUT can well be considered to start the treatment regimen for H. pylori instead of waiting for the histopathological confirmation.{Table 6}

The present study also shows that, the presence of H. pylori infection in gastroduodenal diseases, is quite high, of which, a significant number of cases are associated with atrophy and intestinal metaplasia. Another important observation of this study is that, there is a high association of H. pylori infection in cases of gastric adenocarcinoma. Reviewed literature have revealed that there is a significant risk of progression to cancer in cases of H. pylori gastritis, more so, when they are associated with atrophy and metaplasia. [1] Therefore, it is suggested that detection of the organism at an early stage and eradication with appropriate treatment strategies might prevent disease progression and thus benefit the patients. However, a study of longer duration and with a larger population is required to obtain the actual prevalence of H. pylori in gastroduodenal diseases, in North Eastern region of India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Liu C, Crawford JM. The gastrointestinal tract. In: Kumar V, Abbas AK, Fausto N, editors. Robbins and Cotran Pathologic Basis of Disease. 8 th ed., Vol. 17. USA: Saunders; 2010. p. 797-873.
2Day DW, Jass JR, Price AB, Shepherd NA, Sloan JS, Talbot IC, et al. Gastritis and related conditions. In: Morson and Dawson's Gastrointestinal Pathology. 4 th ed., Vol. 12. USA: Wiley-Blackwell; 2003. p. 104-31.
3Kashyap B, Kaur IR, Garg PK, Das D, Goel S. 'Test and treat' policy in dyspepsia: Time for a reappraisal. Trop Doct 2012;42:109-11.
4Genta RM, Graham DY. Comparison of biopsy sites for the histopathologic diagnosis of Helicobacter pylori: A topographic study of H. pylori density and distribution. Gastrointest Endosc 1994;40:342-5.
5Basset C, Holton J, Ricci C, Gatta L, Tampieri A, Perna F, et al. Review article: Diagnosis and treatment of Helicobacter: A 2002 updated review. Aliment Pharmacol Ther 2003;17 Suppl 2:89-97.
6Sheehan D, Hrapchak B. Theory and Practice of Histotechnology. 2 nd ed. Ohio: Battelle Press; 1980. p. 155-6.
7Stolte M, Meining A. The updated Sydney system: Classification and grading of gastritis as the basis of diagnosis and treatment. Can J Gastroenterol 2001;15:591-8.
8Watanabe H, Stolte M, Sasako M, Rugge M, Powell SM, Munoz N, et al. Gastric carcinoma. In: Hamilton SR, Aaltonen LA, editors. Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press; 2000. p. 38.
9Ghoshal UC, Tripathi S, Ghoshal U. The Indian enigma of frequent H. pylori infection but infrequent gastric cancer: Is the magic key in Indian diet, host's genetic make up, or friendly bug? Am J Gastroenterol 2007;102:2113-4.
10Ahmed KS, Khan AA, Ahmed I, Tiwari SK, Habeeb A, Ahi JD, et al. Impact of household hygiene and water source on the prevalence and transmission of Helicobacter pylori: A South Indian perspective. Singapore Med J 2007;48:543-9.
11Lynn TV, Bruce MG, Landen M, Beller M, Bulkow L, Gold B, et al. Helicobacter pylori infection among non-Native educators in Alaska. Int J Circumpolar Health 2007;66:135-43.
12Sacco F, Bruce MG, McMahon BJ, Bruden D. A prospective evaluation of 200 upper endoscopies performed in Alaska Native persons. Int J Circumpolar Health 2007;66:144-52.
13Okuda M, Miyashiro E, Booka M, Tsuji T, Nakazawa T. Helicobacter pylori colonization in the first 3 years of life in Japanese children. Helicobacter 2007;12:324-7.
14Chen J, Bu XL, Wang QY, Hu PJ, Chen MH. Decreasing seroprevalence of Helicobacter pylori infection during 1993-2003 in Guangzhou, southern China. Helicobacter 2007;12:164-9.
15Rotimi O, Cairns A, Gray S, Moayyedi P, Dixon MF. Histological identification of Helicobacter pylori: Comparison of staining methods. J Clin Pathol 2000;53:756-9.
16Monteiro L, de Mascarel A, Sarrasqueta AM, Bergey B, Barberis C, Talby P, et al. Diagnosis of Helicobacter pylori infection: Noninvasive methods compared to invasive methods and evaluation of two new tests. Am J Gastroenterol 2001;96:353-8.
17McNulty CA, Wise R. Rapid diagnosis of Campylobacter-associated gastritis. Lancet 1985;1:1443-4.
18Zaitoun AM. Histology compared with chemical testing for urease for rapid detection of Helicobacter pylori in gastric biopsy specimens. J Clin Pathol 1993;46:684-5.
19Goh KL, Cheah PL, Navaratnam P, Chin SC, Xiao SD. HUITAI rapid urease test: A new ultra-rapid biopsy urease test for the diagnosis of Helicobacter pylori infection. J Dig Dis 2007;8:139-42.
20Cutler AF, Havstad S, Ma CK, Blaser MJ, Perez-Perez GI, Schubert TT. Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection. Gastroenterology 1995;109:136-41.