1. Introduction
Helicobacter pylori is a major risk factor for gastric cancer which induces chronic gastritis and precancerous changes such as intestinal metaplasia.1–3 Currently, many kinds of methods that may or may not involve endoscopy are used for investigating H. pylori such as the fecal antigen test, urea breath test, H. pylori antibody test, histology, rapid urease testing, culture, and polymerase chain reaction. These testes are cumbersome, time-consuming and lacking real-time information. Methods based on esophagogastroduodenoscopy (EGD) may serve as an initial guide for possible HP infection. However, it is very difficult to distinguish H. pylori infections in patients undergoing light EGD examinations, and a biopsy from the gastric mucosa is required for these patients, which has risks such as missing pathology and sampling errors and is expensive. Therefore, the development of real-time endoscopic assessments for the diagnosis of H. pylori during endoscopy has emerged.
Magnifying endoscopy improves the demonstration of mucosa details and helps the identification of HP infection. However, it is time-consuming and causes an uncomfortable sensation for the patient thus reduces patients' willingness to receive EGD. Patients with H. pylori infections usually present with diffuse redness of the fundic mucosa.4 Recently, linked color imaging (LCI), which only requires the switch of one button, had been reported to be very useful in H. pylori and flat gastric cancers detection.5–7 For the reason that, it can save examination time and mitigate the patient's unpleasant experience during the procedure. However, there is a lack of direct comparison of performance between LCI and current recommended modality. Therefore, we conducted this study to compare the performance of LCI with that of magnifying endoscopy with standard HP identification methods as reference.
2. Methods
2.1. Study population
This study has obtained ethical approval from the Institutional Review Board of the Chang Gung Memorial Hospital (IRB No. 201600789B0). All patients enrolled in this study were well informed and consented. We enrolled consecutive 122 patients (Table 1) who were scheduled for an EGD for various indications such as epigastric pain, anemia, gastroesophageal reflux disease, suspicion of peptic ulcer disease and liver cirrhosis by physicians at Linkou Chang Gung Memorial Hospital between January 2016 and July 2016. All the procedures were performed by an experienced endoscopist. In this study, we excluded those patients that we already knew had hallow organ perforation, gastric outlet obstruction or patients cannot tolerate the whole procedure other than H. pylori eradication status. 111 patients were under further analyzed who received both LCI only or combined with magnifying endoscopy.
;)
Table 1: Patient characteristics of the study population.
2.2. Process of H. pylori infection diagnosis
At first, the enrolled patients were examined with white light imaging (WLI) followed by LCI. We recorded whether the patient had an H. pylori infection or not according to LCI.
Second, magnifying endoscopy was performed after determining the result by LCI. According to previous reports, patients without collecting venules were considered to have a H. pylori infection.8
Third, the results of LCI and magnifying endoscopy were compared for analysis. An H. pylori infection was considered if either of these results was positive.
Finally, four biopsy specimens were obtained (two from the antrum and two from the body) for histology or rapid urease testing. For patients with disputed results, the urea breath test was also performed. In this study, at least two methods were used to make a definitive diagnosis of an H. pylori infection.
An endoscopic biopsy was performed from both the antrum and greater curvature of the corpus to avoid false negative results.8,9
In this study, we used the Fujifilm laser system (Fujifilm Co., Tokyo, Japan) and EG-L590ZW scope for white light and linked color imaging. LCI is a new observation mode that was recently released. By using narrowband light, high contrast images of the surface of the mucosa could be obtained.
A difference in the illumination light and signal processing emphasized the slight difference in color in infected regions that was close to the normal color of the mucosa. As a result, originally red regions appeared redder and originally white regions appeared whiter, but had natural tones. This method could be helpful in visualizing reddish and brownish areas of the mucosa and detecting inflammation and minute changes in it.
The diagnostic principle is according to Osamu Dohi et al. report, those patients with H. pylori infection has a diffuse, deep red color of the fundic mucosa.7 and under LCI the collecting venules become more obvious (more reddish) as Fig. 1A shows images of no infection and Fig. 1B shows H. pylori infection.
Fig. 1.:
A: No H. pylori infection and show more obvious collecting venules (red circule); B: H. pylori infection showing diffuse reddish to purple color under LCI.
2.3. Comparison between LCI and magnifying endoscopy
To compare the accuracy between LCI and magnifying endoscopy, multiple validity indexes such as sensitivity, specificity and positive predictive value were calculated by three different definition of H. pylori infection, one was the result of LCI indicated positive only, another was depended on magnifying endoscopy individually, the other was as positive if either of above results was positive. The p-value for the sensitivity and specificity difference between those definitions were derived from the McNemar's Test. In addition, we conducted stratified analysis by HP eradication status because HP eradication may affect the screening consequence of H. pylori infection.
2.4. Statistical analysis
The statistical analyses were conducted using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).
3. Results
There were 122 patients enrolled in this study (the male to female ratio was 70:52) and all of them underwent LCI. LCI and magnifying endoscopy were used for 111 patients. In our study group, patients who had taken NSAIDs were excluded to avoid the influence of NSAIDs except for one patient who had undergone COX2-inhibitor therapy. Twelve patients had undergone successful eradication previously. In our study group, 29.51% patients had an H. pylori infection. Patient characteristics are shown in Table 1. The H. pylori infection rate was 36/122 (29.51%) which comparable with our previously report.10
111 received LCI and LCI combined with magnifying endoscopy were enrolled for further analysis. The level of accuracy of the diagnosis of H. pylori infection by LCI, magnifying endoscopy, and both LCI and magnifying endoscopy was 78.38%, 81.98%, and 78.38%, respectively.
The sensitivity level for each group was 70.79%, 80.65%, and 83.87, respectively. The specificity level for each group was 81.25%, 82.5%, and 76.25%, respectively. The positive predictive values for each group were 59.64%, 64.1%, and 57.78%, respectively, and the negative predictive values were 87.84%, 91.67%, and 92.42%, respectively. The P values of sensitivity and specificity did not show significant differences. Detailed results are presented in Table 2.
Table 2: Comparison of validity between LCI and Magnifying endoscopy (n = 111).
In our series, 11 patients had undergone H. pylori eradication before. In these patients, LCI did not show better specificity than magnifying endoscopy (Table 3).
Table 3: Specificity (%) of different screening by the HP eradication status.
4. Discussion
Conventional EGD is generally used for H. pylori detection based on features of the gastric mucosa such as redness, mucosal swelling, and nodular changes, but these features are not specific enough for diagnosis.4 Other kinds of image-enhanced endoscopy (IEE) with or without magnifying endoscopy are also used for H. pylori diagnosis. However, these tests are dependent on the operator, that is, they require operators to be trained by experienced supervisors and need special equipment.11 Besides, IEE combined with magnifying endoscopy techniques are time consuming, provide variable results, and may make patients more uncomfortable. The factors mentioned above contribute to the limitation of the clinical use of magnifying endoscopy in the detection of H. pylori infections in routine practice.
We choose the fundus and high body for the investigation according to the previous reports that Spotty redness of the fundic gland region on histology was considered to reflect mucosal hyperemia due to inflammatory changes.12 A strong correlation with an objective index of redness, the hemoglobin index (IHb), has been reported, suggesting that diffuse redness is the most important feature for diagnosing H. pylori infection.13 As the disappearance of polymorphonucleocytes is a histologically significant change shortly after H. pylori eradication, spotty redness of the fundic gland region is suggested to be related to histological activity.14
In this study, we found that LCI has acceptable sensitivity and high specificity in H. pylori detection and has no significant differences from the other two groups studied. Additionally, in this study we contribute those patients who have vague LCI enhancement to have H. pylori infection. In this case the sensitivity may be underestimated. But we rather overestimate the patients who have H. pylori infection than loos anyone who potentially has H. pylori infection.
In this situation, an endoscopist can quickly distinguish patients who have H. pylori infections from those who do not. Based on these benefits, we could save money, and patients could avoid unnecessary procedures such as biopsies, which would decrease complications including gastric hemorrhages related to biopsies.
In our study, some patients presented with false positive results from LCI; these patients had been infected with H. pylori and had undergone successful eradication before. It might attribute to congested mucosa15 and not totally meet Kazuyoshi Yagi reports.16 This is also the potential limitation of our study because no available data showed the change of collecting venules after H. pylori eradication under LCI. However, LCI still could help us to identify patients who had H. pylori infections after eradication, even the specificity is only 63.64%, and take better care of them, especially if they also have intestinal metaplasia, which is seen as the “point of no return” of precancerous lesions. For these patients, we should arrange regular endoscopy examinations.
In conclusion, we found that LCI could be used as a reliable tool for the diagnosis of H. pylori infections and this method only requires the switch of a button. However, there still have limitations in our study such as small study numbers and without compare to high resolution white light endoscopy.
Acknowledgments
We want to thank the staff of our enoscopic center.
References
1. Cogliano VJ, Baan R, Straif K, Grosse Y, Lauby-Secretan B, El Ghissassi FB, et al. Preventable exposures associated with human cancers.
J Natl Cancer Inst. 2011;103:1827-1839.
2. Fock KM. Review article: the epidemiology and prevention of gastric cancer.
Aliment Pharmacol Ther. 2014;40:250-260.
3. IARC Helicobacter pylori Working Group. Helicobacter pylori eradication as a strategy for gastric cancer prevention. 2015. International Agency for Research on Cancer. Lyon, France. (IARC Working Group Reports, No. 8).
4. Kato T, Yagi N, Kamada T, Shimbo T, Watanabe H, Ida K. Diagnosis of Helicobacter pylori infection in gastric mucosa by endoscopic features: a multicenter prospective study.
Dig Endosc. 2013;25:508-518.
5. Tomie Akira, Oshima Yasuhiro, Obora Akihiro, Kojima Takao, Yagi Nobuaki, Kitae Hiroaki., 2015. Usefulness of linked color imaging (LCI) for diagnosis of Helicobacter pylori (H. pylori) infection, EUGW.
6. Fukuda H, Miura Y, Hayashi Y, Takezawa T, Ino Y, Okada M, et al. Linked color imaging technology facilitates early detection of flat gastric cancers.
Clin J Gastroenterol. 2015;8:385-389.
7. Dohi Osamu, Yagi Nobuaki, Onozawa Yuriko, Kimura-Tsuchiya Reiko, Majima Atsushi, Kitaichi Tomoko, et al. Linked color imaging improves endoscopic diagnosis of active Helicobacter pylori infection.
Endosc Int Open. 2016;4:E800-E805.
8. Nakagawa S, Kato M, Shimizu Y, Nakagawa M, Yamamoto J, Luis PA, et al. Relationship between histopathologic gastritis and mucosal microvascularity: observations with magnifying endoscopy.
Gastrointest Endosc. 2003;58:71-75.
9. Lan HC, Chen TS, Li AF, Chang FY, Lin HC. Additional corpus biopsy enhances the detection of Helicobacter pylori infection in a background of gastritis with atrophy.
BMC Gastroenterol. 2012;12:182.
10. Chiu CT, Hsu CM, Wang CC, Chang JJ, Sung CM, Lin CJ, et al. Randomised clinical trial: sodium alginate oral suspension is non-inferior to omeprazole in the treatment of patients with non-erosive gastroesophageal disease.
Aliment Pharmacol Ther. 2013;38:1054-1064.
11. Yagi K, Nakamura A, Sekine A. Comparison between magnifying endoscopy and histological, culture and urease test findings from the gastric mucosa of the corpus.
Endoscopy. 2002;34:376-381.
12. Hattori T. On cell proliferation and differentiation of fundic mucosa of the golden hamster. Fractographic study combined with microscopy and 3H-thymidine autoradiography.
Cell Tissue Res. 1974;148:213-226.
13. Uchiyama K, Ida K, Okuda J, Asai Y, Ohyama Y, Kuroda M, et al. Correlation of hemoglobin index (IHb) of gastric mucosa with Helicobacter pylori (H.pylori) infection and inflammation of gastric mucosa.
Scand J Gastroenterol. 2004;11:1054-1060.
14. Kato Mototsugu, Terao Shuichi, Adachi Kyoichi, Nakajima Shigemi, Ando Takashi, Yoshida Norimasa, et al. Changes in endoscopic findings of gastritis after cure of
H. pylori infection: multicenter prospective trial.
Dig Endosc. 2013;25:264-273.
15. Watanabe Kazuhiro, Nagata Naoyoshi, Nakashima Ryo. Predictive findings for Helicobacter pylori -uninfected,-infected and -eradicated gastric mucosa: validation study.
World J Gastroenterol. 2013 July 21;19:4374-4379.
16. Yagi Kazuyoshi, Nakamura Atsuo, Sekine Atsuo. Magnifying endoscopy of the gastric body: a comparison of the findings before and after eradication of helicobacter pylori. Dig Endosc. 2002;14(Suppl.):S76-S82.
