Article Search
검색
검색 팝업 닫기

Metrics

Help

  • 1. Aims and Scope

    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

  • 2. Editorial Board

    Editor-in-Chief + MORE

    Editor-in-Chief
    Yong Chan Lee Professor of Medicine
    Director, Gastrointestinal Research Laboratory
    Veterans Affairs Medical Center, Univ. California San Francisco
    San Francisco, USA

    Deputy Editor

    Deputy Editor
    Jong Pil Im Seoul National University College of Medicine, Seoul, Korea
    Robert S. Bresalier University of Texas M. D. Anderson Cancer Center, Houston, USA
    Steven H. Itzkowitz Mount Sinai Medical Center, NY, USA
  • 3. Editorial Office
  • 4. Articles
  • 5. Instructions for Authors
  • 6. File Download (PDF version)
  • 7. Ethical Standards
  • 8. Peer Review

    All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal. A decision about these papers will usually be made within two or three weeks.
    The remaining articles are usually sent to two reviewers. It would be very helpful if you could suggest a selection of reviewers and include their contact details. We may not always use the reviewers you recommend, but suggesting reviewers will make our reviewer database much richer; in the end, everyone will benefit. We reserve the right to return manuscripts in which no reviewers are suggested.

    The final responsibility for the decision to accept or reject lies with the editors. In many cases, papers may be rejected despite favorable reviews because of editorial policy or a lack of space. The editor retains the right to determine publication priorities, the style of the paper, and to request, if necessary, that the material submitted be shortened for publication.

Search

Search

Year

to

Article Type

Original Article

Split Viewer

Dynamic Changes in Helicobacter pylori Status Following Gastric Cancer Surgery

Kichul Yoon1,2, Nayoung Kim1,3, Jaeyeon Kim3, Jung Won Lee3, Hye Seung Lee4, Jong-Chan Lee1, Hyuk Yoon1, Cheol Min Shin1, Young Soo Park1, Sang-Hoon Ahn5, Do Joong Park5, Hyung Ho Kim5, Yoon Jin Lee6, Kyoung-Ho Lee6, Young-Hoon Kim6, Dong Ho Lee1,3

1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, 2Department of Internal Medicine, Seoul Adventist Hospital, Seoul, Korea, 3Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea, 4Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea, 5Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea, 6Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea

Correspondence to: Nayoung Kim, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173beon-gil, Bundang-gu, Seongnam 13620, Korea, Tel: +82-31-787-7008, Fax: +82-31-787-4051, E-mail: nayoungkim49@empas.com

Received: May 1, 2016; Revised: June 18, 2016; Accepted: June 18, 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver 2017;11(2):209-215. https://doi.org/10.5009/gnl16224

Published online November 14, 2016, Published date March 15, 2017

Copyright © Gut and Liver.

Background/Aims

Helicobacter pylori eradication is recommended in patients with early gastric cancer. However, the possibility of spontaneous regression raises a question for clinicians about the need for “retesting” postoperative H. pylori status.

Methods

Patients who underwent curative gastrectomy at Seoul National University Bundang Hospital and had a positive H. pylori status without eradication therapy at the time of gastric cancer diagnosis were prospectively enrolled in this study. H. pylori status and atrophic gastritis (AG) and intestinal metaplasia (IM) histologic status were assessed pre- and postoperatively.

Results

One hundred forty patients (mean age, 59.0 years; 60.7% male) underwent subtotal gastrectomy with B-I (65.0%), B-II (27.1%), Roux-en-Y (4.3%), jejunal interposition (0.7%), or proximal gastrectomy (4.3%). Preoperative presence of AG (62.9%) and IM (72.9%) was confirmed. The mean period between surgery and the last endoscopic follow-up was 38.0±25.6 months. Of the 140 patients, 80 (57.1%) were found to be persistently positive for H. pylori, and 60 (42.9%) showed spontaneous negative conversion at least once during follow-up. Of these 60 patients, eight (13.3%) showed more complex postoperative dynamic changes between negative and positive results. The spontaneous negative conversion group showed a trend of having more postoperative IM compared to the persistent H. pylori group.

Conclusions

A high percentage of spontaneous regression and complex dynamic changes in H. pylori status were observed after partial gastrectomy, especially in individuals with postoperative histological IM. It is better to consider postoperative eradication therapy after retesting for H. pylori.

Keywords: Helicobacter pylori, Postoperation, Eradication

Gastric cancer had been the most common cause of cancer deaths worldwide until the 1990s.1 Although decreasing trends in incidence and mortality rates have been observed, stomach cancer is still the second leading cause of cancer death worldwide.2,3 Chronic infection with Helicobacter pylori is the strongest identified risk factor for stomach cancer with worldwide attributable fraction reaching 89.0%.4 In addition, the prophylactic effect of H. pylori eradication on development of metachronous cancer after endoscopic resection of gastric cancer was reported.5

Asia-Pacific consensus guideline suggested that H. pylori screening and eradication in high-risk populations could probably reduce gastric cancer incidence.6 Thus, H. pylori eradication in patients who underwent subtotal gastrectomy for gastric cancer is strongly recommended. However, there have been a few studies reporting spontaneous regression of H. pylori after subtotal gastrectomy in peptic ulcer disease and gastric cancer patients.7,8 The changes in postoperative H. pylori infection status have been suggested to be related to bile reflux and dramatic change of acid secretion after the surgery, which appear to inhibit the growth of H. pylori in the remnant stomach.811 The possibility of dynamic changes raises a question for clinicians about the need for “retesting” of postoperative H. pylori status.

From this background, the aim of the present study was to evaluate the postoperative changes of H. pylori detection and to analyze the factors which affect this dynamic changes of in H. pylori infection status after gastric cancer surgery.

1. Subjects

Patients who underwent gastric cancer surgery at Seoul National University Bundang Hospital with positive H. pylori status at the time of cancer diagnosis between December 2010 and July 2014 were prospectively enrolled. All gastric cancer patients were histologically confirmed to have gastric adenocarcinoma by surgery. Subjects with a history of previous gastric cancer or gastric surgery, eradication therapy before surgery, severe concomitant illness, and treatment with steroids or nonsteroidal anti-inflammatory drugs, use of proton pump inhibitors (PPI) or antibiotics within 4 weeks were excluded. Every enrolled patient underwent postoperative H. pylori status evaluation.

This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital and written informed consent was obtained from all participants (IRB number: B-1510/320-116).

2. H. pylori tests and histology

Preoperatively, four biopsy specimens were obtained from the antrum and the mid body of the stomach, respectively. After surgery, three tissue samples from lesser curvature and greater curvature of remained body were biopsied. Both Campylobacter like organism (CLO) test and Giemsa stain were done on every patient pre- and postoperatively.

Tissue sections were stained with modified Giemsa to prove the presence of H. pylori. H. pylori status was additionally assessed by rapid urease test (CLO test; Delta West, Bentley, Australia) and culture studies. Protocols for the biopsy-based tests have been previously described in detail.12 Specific immunoglobulin G (IgG) for H. pylori was screened by an enzyme-linked immunosorbent assay (ELISA) in each subject’s serum (Genedia H. pylori ELISA; Green Cross Medical Science Corp., Eumsung, Korea); Korean strain was used as antigen in this H. pylori antibody test.13 Each patient was asked about their history of H. pylori eradication. If all of these four tests and history of H. pylori eradication were negative, the subject was determined as H. pylori-negative status. Past infection was defined as being positive for H. pylori IgG or having the history of eradication with negative result of abovementioned three invasive tests. Degree of inflammatory cell infiltration, atrophic gastritis (AG), and intestinal metaplasia (IM) were confirmed by hematoxylin and eosin stain who was unaware of the patient history and endoscopic findings. The histological features of the gastric mucosa were recorded using an updated Sydney scoring system (i.e., 0=none, 1=slight, 2=moderate, and 3=marked).14 When the specimens were not prepared well enough to correct evaluate full-thickness gastric mucosa due to problems such as improper fixation, inaccurate orientation, and section inappropriateness, or whenever inflammation prevented a clear distinction between non-atrophic and atrophic phenotypes samples were classified as inapplicable for atrophy.15

3. H. pylori eradication therapy and follow-up

The patients with persistent H. pylori infection after surgery received eradication therapy, consisting of a standard dose of a PPI twice a day, amoxicillin 1 g twice a day, and clarithromycin 500 mg twice a day for 1 week. Eradication of H. pylori was confirmed by 13C urea breath test (UBT), which took place 4 weeks after the completion of treatment. PPI was discontinued for 4 weeks before UBT. In addition, the follow-up endoscopy was done every year after the eradication of H. pylori. Three biopsy-based tests to evaluate H. pylori and histological grading of AG and IM were performed as noted above. Spontaneous H. pylori-negative conversion was defined as all of the histology findings for H. pylori were negative at least once during the follow-up period after surgery. “Dynamic changes” means the presence of another change in H. pylori status after being confirmed as “spontaneous negative conversion.”

4. Statistical analysis

All statistical analyses were performed using the SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA). Student t-test and chi-square test were used to compare the baseline characteristics between persistently positive- and spontaneous negative conversion group. To assess the factors related with postoperative H. pylori status, student t-test, chi-square test, and Fisher exact test were performed. Differences were considered significant when p-values were <0.05.

1. Baseline characteristics

A total of 140 biopsy proven stomach cancer patients (mean age, 59.0 years; 85 male [60.7%]) with known H. pylori status at the time of diagnosis were enrolled (Table 1). Every patient on baseline was found to be positive on at least one out of three H. pylori tests (CLO test, Giemsa stain, or H. pylori IgG). H. pylori IgG the test was done on 80 patients (57.1%) at the time of enrollment. Among them, three patients showed negative result for the serologic test.

All patients had undergone gastrectomy (subtotal gastrectomy with B-I, 91 [65.0%]; B-II, 38 [27.1%]; Roux-en-Y, 4 [4.3%]; jejunal interposition, 1 [0.7%]; proximal gastrectomy, 6 [4.3%]). There were 69 (49.3%) of intestinal and 69 (49.3%) of diffuse type cancers according to Lauren classification. Mean size of cancer lesion was 3.79±2.3 cm. Histologic AG and IM were confirmed to be present (AG, 88 [62.9%]; IM, 102 [72.9%]) before surgery.

2. Postoperative endoscopic follow-up

After surgery, annual follow-up was planned, and all 140 patients underwent endoscopy at least once (up to seven times). Forty-four patients (31.5%) were followed up more than twice. The mean interval between surgery and the first follow-up was 25.3±19.8 months. Mean follow-up period between surgery and the last endoscopic follow up was 38.0±25.6 months (Table 2).

3. Eradication therapy after surgery

All patients had their H. pylori status rechecked with both CLO test and Giemsa stain after surgery, before making decision regarding eradication therapy. Among them, 80 patients (57.1%) were found to be persistently positive and 45 of them underwent eradication therapy with success rate of 62.2% (Fig. 1). Sixty patients (42.9%) showed spontaneous negative conversion at least once during the follow-up period with negative test results from both CLO test and Giemsa stain. Dynamic changes between negative and positive results were noted in eight patients (5.7%), who were included in the spontaneous negative conversion group.

4. Spontaneous H. pylori-negative conversion rate after surgery and dynamic changes of H. pylori

After surgery, 60 patients (42.9%) showed spontaneous H. pylori-negative conversion among 140 patients who underwent endoscopy at least once (up to seven times) (Fig. 1). Among the 60 patients, 43 patients (71.6%) were followed-up only once and nine patients (15%) received endoscopy at least twice. In case of eight patients (13.3%), H. pylori status showed more complex dynamic changes between negative and positive results at each follow-up (Fig. 1).

5. Comparison between persistently H. pylori-positive group and spontaneous H. pylori-negative conversion group after surgery

We compared variables between the patients who had persistent H. pylori infection (n=80, 57.1%) and those with spontaneous negative conversion (n=60, 42.9%) after gastrectomy. There was no statistically significant difference in age, gender, surgery type, alcohol consumption or cigarette smoking between two groups.

The distribution for the presence of AG and IM was not different between two groups at the baseline biopsy. However, there were significant changes based on the first postoperative biopsy results (Table 3). Spontaneous negative conversion group showed trend of having more IM compared to the H. pylori persistent group. However, in case of AG, it showed a reversed result. There were 20 (33.3%) and 16 (20.0%) inapplicable cases in the negative conversion group and in the persistently positive group, respectively (Table 3).

It is controversial whether H. pylori eradication is effective in the prevention of gastric cancer in postgastrectomy patients.5,16 However, most guidelines include early gastric cancer as an indication for H. pylori eradication based on the reports regarding the prevention of metachronous cancer.5,6,17 Although the effect of subtotal gastrectomy on H. pylori infection status has not been fully evaluated, some reports suggested spontaneous regression of H. pylori after partial gastrectomy in patients with peptic ulcer disease and gastric cancer.7,9 Furthermore, the prevalence of H. pylori infection or colonization was significantly lower in the group who underwent distal gastrectomy than that of the control group in peptic ulcer patients.7 As bile reflux is more severe in remnant stomach after distal gastrectomy than in control, it might be the cause for the lower rate of H. pylori infection.8,9 In addition, some studies suggested that the spontaneous H. pylori clearance was related to the type of gastric reconstruction procedures and the time after the operation. That is, Billroth-II procedure had a higher bile reflux rate and a lower H. pylori infection prevalence than the Billroth-I procedure.18 In contrast, there have been reports on H. pylori reinfection after partial gastrectomy in benign diseases,19 and the remnant mucosa after gastric resection for duodenal ulcer and gastric cancer was suggested to be a favorable environment for H. pylori infection.20 These various reports necessitate further investigation on the natural course of H. pylori status after gastric surgery.

In the present study, spontaneous negative conversion of H. pylori frequently occurred in patients who had not received the eradication therapy after partial gastrectomy. It is in accordance with the earlier studies showing that almost 40% of patients had spontaneous regression postoperatively.8,11 However, H. pylori status could fluctuate due to the limitation of H. pylori tests especially in the background of atrophy and IM.12 Previous studies have shown the limitations of invasive and noninvasive tests in detecting H. pylori infection in patients with AG and IM.2123 The bacterial load of H. pylori decreases as the gastric atrophy and IM progresses,23 and sparse bacteria have uneven distribution in the stomach. Our result shows that postoperative histology in the spontaneous negative conversion group showed more IM than persistently positive group, supporting this harsh environment of IM kicks out the H. pylori spontaneously. However, atrophy (loss of appropriate glands) showed reverse results to the IM and it might be originated high proportion of inapplicable cases. In addition, the possibility of false negative results in the AG or IM could have been existed because the distribution is not even, especially adequately interpreted cases for histologic atrophy was so small.

In our study, there was no significant difference between spontaneous conversion and persistently positive groups according to surgery type, which could affect the bile reflux. It could suggest that IM could be a more important factor for the survival of H. pylori than bile reflux.

As remnant stomach has different anatomic and biological environment, there have been several studies to investigate the efficacy of postoperative eradication therapy.11,2427 However, the number of subjects in those studies was relatively small, and the time from the operation to the eradication therapy was too long. Moreover, eradication regimen in some studies is not applicable nowadays because PPI based dual therapy was used instead of PPI-based triple therapy in the earlier studies.24,25 In addition, it is sometimes difficult to interpret the eradication in the gastric remnant as dynamic changes frequently occur. Therefore, careful serial follow-up is necessary to define “true spontaneous regression.”

The present study is a comprehensive study with relatively long duration of follow-up around 3 years. It also confirmed H. pylori status with serial multiple methods including histology with modified Giemsa stain and CLO test for all the subjects. However, our study also has limitation of being conducted as a single-center study with relatively small number of patients even the inclusion period lasted nearly 4 years. In addition, among 60 patients who had spontaneous negative conversion, 43 (72%) subjects were followed up only once. If they had been tested more times, dynamic changes might have been described. Another limitation is that we have not analyzed in detail regarding the effect of cancer chemotherapy on the dynamic change of H. pylori. That is, we did not collect the exact data and analyzed the effect even though most of the patients with advanced gastric cancer (49 subjects, 35% of the enrolled patients) had undergone adjuvant chemotherapy. However, as chemotherapeutic agents are not antibiotics and the proportion of advanced gastric cancer was rather small in this study, we suppose its role might be minor in the spontaneous negative conversion than IM.

In conclusion, we observed that there was relatively high percentage of spontaneous regression and dynamic changes in status of H. pylori after partial gastrectomy, with a trend of having more histologic IM. Postoperative H. pylori eradication therapy had better be performed after retest for H. pylori, and sometimes serial follow-up tests are necessary before decision.

This work was supported by the Global Core Research Center (GCRC) grant (2011-0030001) from the National Research Foundation (NRF), Ministry of Education, Science and Technology (MEST), Republic of Korea.

Baseline Characteristics of 140 Patients with Biopsy-Confirmed Stomach Cancer

VariableValue
Age, yr59.0±11.54
Sex
 Male85 (60.7)
 Female55 (39.3)
Lauren classification
 Intestinal69 (49.3)
 Diffuse69 (49.3)
 Mixed2 (1.4)
EGC or AGC
 EGC91 (65.0)
 AGC49 (35.0)
Cancer location
 Antrum63 (45.0)
 Body65 (46.4)
 Antrum and body7 (5.0)
 Cardia5 (3.6)
Surgery type
 Subtotal gastrectomy
  Billroth I91 (65.0)
  Billroth II38 (27.1)
  Roux-en-Y4 (4.3)
  With jejunal interposition1 (0.7)
 Proximal gastrectomy6 (4.3)
Smoking
 Never57 (40.7)
 Current29 (20.7)
 Ex-smoker54 (38.6)
Alcohol
 None69 (49.3)
 Social53 (37.9)
 Heavy*18 (12.9)
Atrophic gastritis
 Negative34 (24.3)
 Positive88 (62.9)
 Not applicable18 (12.9)
Intestinal metaplasia
 Negative38 (27.1)
 Positive102 (72.9)

Data are presented as mean±SD or number (%).

EGC, early gastric cancer; AGC, advanced gastric cancer.

*More than 200 g/wk.


Postoperative Endoscopic Follow-Up Sessions

No. of follow-up timesNo. (%)
Up to 1st time96 (68.6)
Up to 2nd time19 (13.6)
Up to 3rd–7th time25 (17.9)

Comparison of Persistently Helicobacter pylori-Positive and -Negative Conversion Groups after Surgery (n=140)

VariableNegative conversion* (n=60)Persistently positive (n=80)p-value
Surgery0.261
 Subtotal B-I34 (56.7)57 (71.3)
 Subtotal B-II20 (33.3)18 (22.5)
 Subtotal Roux-en-Y2 (3.3)2 (2.5)
 Subtotal with jejunal interposition01 (1.3)
 Proximal gastrectomy4 (6.7)2 (2.5)
Age, yr58.95±11.0959.09±11.930.944
Male sex36 (60.0)49 (61.3)1.000
Smoking0.168
 Never22 (36.7)35 (43.8)
 Current17 (28.3)12 (15.0)
 Ex-smoker21 (35.0)33 (41.3)
Alcohol0.971
 None30 (50.5)39 (48.8)
 Social22 (36.7)31 (38.8)
 Heavy8 (13.3)10 (12.5)
Atrophic gastritis (baseline)0.677
 Negative16 (26.7)18 (22.5)
 Positive38 (63.3)50 (62.5)
 Inapplicable6 (10.0)12 (15.0)
Atrophic gastritis (1st follow-up)0.008
 Negative32 (53.3)36 (45.0)
 Positive8 (13.3)20 (25.0)
 Inapplicable20 (33.3)16 (20.0)
 Not available08 (10.0)
Intestinal metaplasia (baseline)0.340
 Negative19 (31.7)19 (23.8)
 Positive41 (68.3)61 (76.3)
Intestinal metaplasia (1st follow-up)0.001
 Negative38 (63.3)59 (73.8)
 Positive22 (36.7)13 (16.3)
 Not available08 (10.0)

Data are presented as number (%) or mean±SD.

*Spontaneous conversion to H. pylori-negative status at least once during follow-up period;

Statistically significant correlations (p<0.05).


  1. Pisani, P, Parkin, DM, Bray, F, and Ferlay, J (1999). Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer. 83, 18-29.
    Pubmed CrossRef
  2. Arnold, M, Moore, SP, Hassler, S, Ellison-Loschmann, L, Forman, D, and Bray, F (2014). The burden of stomach cancer in indigenous populations: a systematic review and global assessment. Gut. 63, 64-71.
    CrossRef
  3. Torre, LA, Bray, F, Siegel, RL, Ferlay, J, Lortet-Tieulent, J, and Jemal, A (2015). Global cancer statistics, 2012. CA Cancer J Clin. 65, 87-108.
    Pubmed CrossRef
  4. Plummer, M, Franceschi, S, Vignat, J, Forman, D, and de Martel, C (2015). Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer. 136, 487-490.
    CrossRef
  5. Fukase, K, Kato, M, and Kikuchi, S (2008). Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 372, 392-397.
    Pubmed CrossRef
  6. Fock, KM, Talley, N, and Moayyedi, P (2008). Asia-Pacific consensus guidelines on gastric cancer prevention. J Gastroenterol Hepatol. 23, 351-365.
    Pubmed CrossRef
  7. Bair, MJ, Wu, MS, and Chang, WH (2009). Spontaneous clearance of Helicobacter pylori colonization in patients with partial gastrectomy: correlates with operative procedures and duration after operation. J Formos Med Assoc. 108, 13-19.
    Pubmed CrossRef
  8. Abe, H, Murakami, K, and Satoh, S (2005). Influence of bile reflux and Helicobacter pylori infection on gastritis in the remnant gastric mucosa after distal gastrectomy. J Gastroenterol. 40, 563-569.
    Pubmed CrossRef
  9. Li, XB, Lu, H, Chen, HM, Chen, XY, and Ge, ZZ (2008). Role of bile reflux and Helicobacter pylori infection on inflammation of gastric remnant after distal gastrectomy. J Dig Dis. 9, 208-212.
    Pubmed CrossRef
  10. Johannesson, KA, Hammar, E, and Staël von Holstein, C (2003). Mucosal changes in the gastric remnant: long-term effects of bile reflux diversion and Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 15, 35-40.
    Pubmed CrossRef
  11. Suh, S, Nah, JC, and Uhm, MS (2012). Changes in prevalence of Helicobacter pylori infection after subtotal gastrectomy. Hepatogastroenterology. 59, 646-648.
    Pubmed
  12. Kim, SE, Park, YS, and Kim, N (2013). Effect of Helicobacter pylori eradication on functional dyspepsia. J Neurogastroenterol Motil. 19, 233-243.
    Pubmed KoreaMed CrossRef
  13. Kim, HJ, Hwang, SW, and Kim, N (2014). Helicobacter pylori and molecular markers as prognostic indicators for gastric cancer in Korea. J Cancer Prev. 19, 56-67.
    Pubmed KoreaMed CrossRef
  14. Dixon, MF, Genta, RM, Yardley, JH, and Correa, P (1996). Classification and grading of gastritis: the updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 20, 1161-1181.
    Pubmed CrossRef
  15. Rugge, M, Correa, P, and Dixon, MF (2002). Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading. Aliment Pharmacol Ther. 16, 1249-1259.
    Pubmed CrossRef
  16. Maehata, Y, Nakamura, S, and Fujisawa, K (2012). Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer. Gastrointest Endosc. 75, 39-46.
    CrossRef
  17. Shiota, S, Murakami, K, Fujioka, T, and Yamaoka, Y (2010). Population-based strategies for Helicobacter pylori-associated disease management: a Japanese perspective. Expert Rev Gastroenterol Hepatol. 4, 149-156.
    Pubmed KoreaMed CrossRef
  18. Fukuhara, K, Osugi, H, and Takada, N (2004). Duodenogastric reflux eradicates Helicobacter pylori after distal gastrectomy. Hepatogastroenterology. 51, 1548-1550.
    Pubmed
  19. Csendes, A, Smok, G, and Burgos, AM (2008). Behavior of the infection by Helicobacter pylori of the gastric remnant after subtotal gastrectomy and Roux-en-Y anastomosis for benign diseases. J Gastrointest Surg. 12, 1508-1511.
    Pubmed CrossRef
  20. Giuliani, A, Galati, G, Demoro, M, Scimò, M, Pecorella, I, and Basso, L (2010). Screening of Helicobacter pylori infection after gastrectomy for cancer or peptic ulcer: results of a cohort study. Arch Surg. 145, 962-967.
    Pubmed CrossRef
  21. Korstanje, A, van Eeden, S, and Offerhaus, GJ (2006). The 13carbon urea breath test for the diagnosis of Helicobacter pylori infection in subjects with atrophic gastritis: evaluation in a primary care setting. Aliment Pharmacol Ther. 24, 643-650.
    Pubmed CrossRef
  22. Onoda, N, Maeda, K, Sawada, T, Wakasa, K, Arakawa, T, and Chung, KH (2001). Prevalence of Helicobacter pylori infection in gastric remnant after distal gastrectomy for primary gastric cancer. Gastric Cancer. 4, 87-92.
    Pubmed CrossRef
  23. Kang, HY, Kim, N, and Park, YS (2006). Progression of atrophic gastritis and intestinal metaplasia drives Helicobacter pylori out of the gastric mucosa. Dig Dis Sci. 51, 2310-2315.
    Pubmed CrossRef
  24. Matsukura, N, Tajiri, T, and Kato, S (2003). Helicobacter pylori eradication therapy for the remnant stomach after gastrectomy. Gastric Cancer. 6, 100-107.
    Pubmed
  25. Rino, Y, Imada, T, and Shiozawa, M (2000). Helicobacter pylori of remnant stomach and optimal dose of amoxicillin for eradicating Helicobacter pylori. Hepatogastroenterology. 47, 567-570.
    Pubmed
  26. Kim, CG, Song, HJ, and Kook, MC (2008). Preoperative versus postoperative Helicobacter pylori eradication therapy in gastric cancer patients: a randomized trial. Am J Gastroenterol. 103, 48-54.
    CrossRef
  27. Sheu, BS, Yang, HB, and Wang, YL (2002). Stool antigen assay to screen H. pylori infection and to assess the success of 3-day and 7-day eradication therapy in the patients with partial gastrectomy. Helicobacter. 7, 199-204.
    Pubmed CrossRef

Article

Original Article

Gut and Liver 2017; 11(2): 209-215

Published online March 15, 2017 https://doi.org/10.5009/gnl16224

Copyright © Gut and Liver.

Dynamic Changes in Helicobacter pylori Status Following Gastric Cancer Surgery

Kichul Yoon1,2, Nayoung Kim1,3, Jaeyeon Kim3, Jung Won Lee3, Hye Seung Lee4, Jong-Chan Lee1, Hyuk Yoon1, Cheol Min Shin1, Young Soo Park1, Sang-Hoon Ahn5, Do Joong Park5, Hyung Ho Kim5, Yoon Jin Lee6, Kyoung-Ho Lee6, Young-Hoon Kim6, Dong Ho Lee1,3

1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, 2Department of Internal Medicine, Seoul Adventist Hospital, Seoul, Korea, 3Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea, 4Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea, 5Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea, 6Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea

Correspondence to:Nayoung Kim, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173beon-gil, Bundang-gu, Seongnam 13620, Korea, Tel: +82-31-787-7008, Fax: +82-31-787-4051, E-mail: nayoungkim49@empas.com

Received: May 1, 2016; Revised: June 18, 2016; Accepted: June 18, 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Helicobacter pylori eradication is recommended in patients with early gastric cancer. However, the possibility of spontaneous regression raises a question for clinicians about the need for “retesting” postoperative H. pylori status.

Methods

Patients who underwent curative gastrectomy at Seoul National University Bundang Hospital and had a positive H. pylori status without eradication therapy at the time of gastric cancer diagnosis were prospectively enrolled in this study. H. pylori status and atrophic gastritis (AG) and intestinal metaplasia (IM) histologic status were assessed pre- and postoperatively.

Results

One hundred forty patients (mean age, 59.0 years; 60.7% male) underwent subtotal gastrectomy with B-I (65.0%), B-II (27.1%), Roux-en-Y (4.3%), jejunal interposition (0.7%), or proximal gastrectomy (4.3%). Preoperative presence of AG (62.9%) and IM (72.9%) was confirmed. The mean period between surgery and the last endoscopic follow-up was 38.0±25.6 months. Of the 140 patients, 80 (57.1%) were found to be persistently positive for H. pylori, and 60 (42.9%) showed spontaneous negative conversion at least once during follow-up. Of these 60 patients, eight (13.3%) showed more complex postoperative dynamic changes between negative and positive results. The spontaneous negative conversion group showed a trend of having more postoperative IM compared to the persistent H. pylori group.

Conclusions

A high percentage of spontaneous regression and complex dynamic changes in H. pylori status were observed after partial gastrectomy, especially in individuals with postoperative histological IM. It is better to consider postoperative eradication therapy after retesting for H. pylori.

Keywords: Helicobacter pylori, Postoperation, Eradication

INTRODUCTION

Gastric cancer had been the most common cause of cancer deaths worldwide until the 1990s.1 Although decreasing trends in incidence and mortality rates have been observed, stomach cancer is still the second leading cause of cancer death worldwide.2,3 Chronic infection with Helicobacter pylori is the strongest identified risk factor for stomach cancer with worldwide attributable fraction reaching 89.0%.4 In addition, the prophylactic effect of H. pylori eradication on development of metachronous cancer after endoscopic resection of gastric cancer was reported.5

Asia-Pacific consensus guideline suggested that H. pylori screening and eradication in high-risk populations could probably reduce gastric cancer incidence.6 Thus, H. pylori eradication in patients who underwent subtotal gastrectomy for gastric cancer is strongly recommended. However, there have been a few studies reporting spontaneous regression of H. pylori after subtotal gastrectomy in peptic ulcer disease and gastric cancer patients.7,8 The changes in postoperative H. pylori infection status have been suggested to be related to bile reflux and dramatic change of acid secretion after the surgery, which appear to inhibit the growth of H. pylori in the remnant stomach.811 The possibility of dynamic changes raises a question for clinicians about the need for “retesting” of postoperative H. pylori status.

From this background, the aim of the present study was to evaluate the postoperative changes of H. pylori detection and to analyze the factors which affect this dynamic changes of in H. pylori infection status after gastric cancer surgery.

MATERIALS AND METHODS

1. Subjects

Patients who underwent gastric cancer surgery at Seoul National University Bundang Hospital with positive H. pylori status at the time of cancer diagnosis between December 2010 and July 2014 were prospectively enrolled. All gastric cancer patients were histologically confirmed to have gastric adenocarcinoma by surgery. Subjects with a history of previous gastric cancer or gastric surgery, eradication therapy before surgery, severe concomitant illness, and treatment with steroids or nonsteroidal anti-inflammatory drugs, use of proton pump inhibitors (PPI) or antibiotics within 4 weeks were excluded. Every enrolled patient underwent postoperative H. pylori status evaluation.

This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital and written informed consent was obtained from all participants (IRB number: B-1510/320-116).

2. H. pylori tests and histology

Preoperatively, four biopsy specimens were obtained from the antrum and the mid body of the stomach, respectively. After surgery, three tissue samples from lesser curvature and greater curvature of remained body were biopsied. Both Campylobacter like organism (CLO) test and Giemsa stain were done on every patient pre- and postoperatively.

Tissue sections were stained with modified Giemsa to prove the presence of H. pylori. H. pylori status was additionally assessed by rapid urease test (CLO test; Delta West, Bentley, Australia) and culture studies. Protocols for the biopsy-based tests have been previously described in detail.12 Specific immunoglobulin G (IgG) for H. pylori was screened by an enzyme-linked immunosorbent assay (ELISA) in each subject’s serum (Genedia H. pylori ELISA; Green Cross Medical Science Corp., Eumsung, Korea); Korean strain was used as antigen in this H. pylori antibody test.13 Each patient was asked about their history of H. pylori eradication. If all of these four tests and history of H. pylori eradication were negative, the subject was determined as H. pylori-negative status. Past infection was defined as being positive for H. pylori IgG or having the history of eradication with negative result of abovementioned three invasive tests. Degree of inflammatory cell infiltration, atrophic gastritis (AG), and intestinal metaplasia (IM) were confirmed by hematoxylin and eosin stain who was unaware of the patient history and endoscopic findings. The histological features of the gastric mucosa were recorded using an updated Sydney scoring system (i.e., 0=none, 1=slight, 2=moderate, and 3=marked).14 When the specimens were not prepared well enough to correct evaluate full-thickness gastric mucosa due to problems such as improper fixation, inaccurate orientation, and section inappropriateness, or whenever inflammation prevented a clear distinction between non-atrophic and atrophic phenotypes samples were classified as inapplicable for atrophy.15

3. H. pylori eradication therapy and follow-up

The patients with persistent H. pylori infection after surgery received eradication therapy, consisting of a standard dose of a PPI twice a day, amoxicillin 1 g twice a day, and clarithromycin 500 mg twice a day for 1 week. Eradication of H. pylori was confirmed by 13C urea breath test (UBT), which took place 4 weeks after the completion of treatment. PPI was discontinued for 4 weeks before UBT. In addition, the follow-up endoscopy was done every year after the eradication of H. pylori. Three biopsy-based tests to evaluate H. pylori and histological grading of AG and IM were performed as noted above. Spontaneous H. pylori-negative conversion was defined as all of the histology findings for H. pylori were negative at least once during the follow-up period after surgery. “Dynamic changes” means the presence of another change in H. pylori status after being confirmed as “spontaneous negative conversion.”

4. Statistical analysis

All statistical analyses were performed using the SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA). Student t-test and chi-square test were used to compare the baseline characteristics between persistently positive- and spontaneous negative conversion group. To assess the factors related with postoperative H. pylori status, student t-test, chi-square test, and Fisher exact test were performed. Differences were considered significant when p-values were <0.05.

RESULTS

1. Baseline characteristics

A total of 140 biopsy proven stomach cancer patients (mean age, 59.0 years; 85 male [60.7%]) with known H. pylori status at the time of diagnosis were enrolled (Table 1). Every patient on baseline was found to be positive on at least one out of three H. pylori tests (CLO test, Giemsa stain, or H. pylori IgG). H. pylori IgG the test was done on 80 patients (57.1%) at the time of enrollment. Among them, three patients showed negative result for the serologic test.

All patients had undergone gastrectomy (subtotal gastrectomy with B-I, 91 [65.0%]; B-II, 38 [27.1%]; Roux-en-Y, 4 [4.3%]; jejunal interposition, 1 [0.7%]; proximal gastrectomy, 6 [4.3%]). There were 69 (49.3%) of intestinal and 69 (49.3%) of diffuse type cancers according to Lauren classification. Mean size of cancer lesion was 3.79±2.3 cm. Histologic AG and IM were confirmed to be present (AG, 88 [62.9%]; IM, 102 [72.9%]) before surgery.

2. Postoperative endoscopic follow-up

After surgery, annual follow-up was planned, and all 140 patients underwent endoscopy at least once (up to seven times). Forty-four patients (31.5%) were followed up more than twice. The mean interval between surgery and the first follow-up was 25.3±19.8 months. Mean follow-up period between surgery and the last endoscopic follow up was 38.0±25.6 months (Table 2).

3. Eradication therapy after surgery

All patients had their H. pylori status rechecked with both CLO test and Giemsa stain after surgery, before making decision regarding eradication therapy. Among them, 80 patients (57.1%) were found to be persistently positive and 45 of them underwent eradication therapy with success rate of 62.2% (Fig. 1). Sixty patients (42.9%) showed spontaneous negative conversion at least once during the follow-up period with negative test results from both CLO test and Giemsa stain. Dynamic changes between negative and positive results were noted in eight patients (5.7%), who were included in the spontaneous negative conversion group.

4. Spontaneous H. pylori-negative conversion rate after surgery and dynamic changes of H. pylori

After surgery, 60 patients (42.9%) showed spontaneous H. pylori-negative conversion among 140 patients who underwent endoscopy at least once (up to seven times) (Fig. 1). Among the 60 patients, 43 patients (71.6%) were followed-up only once and nine patients (15%) received endoscopy at least twice. In case of eight patients (13.3%), H. pylori status showed more complex dynamic changes between negative and positive results at each follow-up (Fig. 1).

5. Comparison between persistently H. pylori-positive group and spontaneous H. pylori-negative conversion group after surgery

We compared variables between the patients who had persistent H. pylori infection (n=80, 57.1%) and those with spontaneous negative conversion (n=60, 42.9%) after gastrectomy. There was no statistically significant difference in age, gender, surgery type, alcohol consumption or cigarette smoking between two groups.

The distribution for the presence of AG and IM was not different between two groups at the baseline biopsy. However, there were significant changes based on the first postoperative biopsy results (Table 3). Spontaneous negative conversion group showed trend of having more IM compared to the H. pylori persistent group. However, in case of AG, it showed a reversed result. There were 20 (33.3%) and 16 (20.0%) inapplicable cases in the negative conversion group and in the persistently positive group, respectively (Table 3).

DISCUSSION

It is controversial whether H. pylori eradication is effective in the prevention of gastric cancer in postgastrectomy patients.5,16 However, most guidelines include early gastric cancer as an indication for H. pylori eradication based on the reports regarding the prevention of metachronous cancer.5,6,17 Although the effect of subtotal gastrectomy on H. pylori infection status has not been fully evaluated, some reports suggested spontaneous regression of H. pylori after partial gastrectomy in patients with peptic ulcer disease and gastric cancer.7,9 Furthermore, the prevalence of H. pylori infection or colonization was significantly lower in the group who underwent distal gastrectomy than that of the control group in peptic ulcer patients.7 As bile reflux is more severe in remnant stomach after distal gastrectomy than in control, it might be the cause for the lower rate of H. pylori infection.8,9 In addition, some studies suggested that the spontaneous H. pylori clearance was related to the type of gastric reconstruction procedures and the time after the operation. That is, Billroth-II procedure had a higher bile reflux rate and a lower H. pylori infection prevalence than the Billroth-I procedure.18 In contrast, there have been reports on H. pylori reinfection after partial gastrectomy in benign diseases,19 and the remnant mucosa after gastric resection for duodenal ulcer and gastric cancer was suggested to be a favorable environment for H. pylori infection.20 These various reports necessitate further investigation on the natural course of H. pylori status after gastric surgery.

In the present study, spontaneous negative conversion of H. pylori frequently occurred in patients who had not received the eradication therapy after partial gastrectomy. It is in accordance with the earlier studies showing that almost 40% of patients had spontaneous regression postoperatively.8,11 However, H. pylori status could fluctuate due to the limitation of H. pylori tests especially in the background of atrophy and IM.12 Previous studies have shown the limitations of invasive and noninvasive tests in detecting H. pylori infection in patients with AG and IM.2123 The bacterial load of H. pylori decreases as the gastric atrophy and IM progresses,23 and sparse bacteria have uneven distribution in the stomach. Our result shows that postoperative histology in the spontaneous negative conversion group showed more IM than persistently positive group, supporting this harsh environment of IM kicks out the H. pylori spontaneously. However, atrophy (loss of appropriate glands) showed reverse results to the IM and it might be originated high proportion of inapplicable cases. In addition, the possibility of false negative results in the AG or IM could have been existed because the distribution is not even, especially adequately interpreted cases for histologic atrophy was so small.

In our study, there was no significant difference between spontaneous conversion and persistently positive groups according to surgery type, which could affect the bile reflux. It could suggest that IM could be a more important factor for the survival of H. pylori than bile reflux.

As remnant stomach has different anatomic and biological environment, there have been several studies to investigate the efficacy of postoperative eradication therapy.11,2427 However, the number of subjects in those studies was relatively small, and the time from the operation to the eradication therapy was too long. Moreover, eradication regimen in some studies is not applicable nowadays because PPI based dual therapy was used instead of PPI-based triple therapy in the earlier studies.24,25 In addition, it is sometimes difficult to interpret the eradication in the gastric remnant as dynamic changes frequently occur. Therefore, careful serial follow-up is necessary to define “true spontaneous regression.”

The present study is a comprehensive study with relatively long duration of follow-up around 3 years. It also confirmed H. pylori status with serial multiple methods including histology with modified Giemsa stain and CLO test for all the subjects. However, our study also has limitation of being conducted as a single-center study with relatively small number of patients even the inclusion period lasted nearly 4 years. In addition, among 60 patients who had spontaneous negative conversion, 43 (72%) subjects were followed up only once. If they had been tested more times, dynamic changes might have been described. Another limitation is that we have not analyzed in detail regarding the effect of cancer chemotherapy on the dynamic change of H. pylori. That is, we did not collect the exact data and analyzed the effect even though most of the patients with advanced gastric cancer (49 subjects, 35% of the enrolled patients) had undergone adjuvant chemotherapy. However, as chemotherapeutic agents are not antibiotics and the proportion of advanced gastric cancer was rather small in this study, we suppose its role might be minor in the spontaneous negative conversion than IM.

In conclusion, we observed that there was relatively high percentage of spontaneous regression and dynamic changes in status of H. pylori after partial gastrectomy, with a trend of having more histologic IM. Postoperative H. pylori eradication therapy had better be performed after retest for H. pylori, and sometimes serial follow-up tests are necessary before decision.

ACKNOWLEDGEMENTS

This work was supported by the Global Core Research Center (GCRC) grant (2011-0030001) from the National Research Foundation (NRF), Ministry of Education, Science and Technology (MEST), Republic of Korea.

Fig 1.

Figure 1.Array
Gut and Liver 2017; 11: 209-215https://doi.org/10.5009/gnl16224

Table 1 Baseline Characteristics of 140 Patients with Biopsy-Confirmed Stomach Cancer

VariableValue
Age, yr59.0±11.54
Sex
 Male85 (60.7)
 Female55 (39.3)
Lauren classification
 Intestinal69 (49.3)
 Diffuse69 (49.3)
 Mixed2 (1.4)
EGC or AGC
 EGC91 (65.0)
 AGC49 (35.0)
Cancer location
 Antrum63 (45.0)
 Body65 (46.4)
 Antrum and body7 (5.0)
 Cardia5 (3.6)
Surgery type
 Subtotal gastrectomy
  Billroth I91 (65.0)
  Billroth II38 (27.1)
  Roux-en-Y4 (4.3)
  With jejunal interposition1 (0.7)
 Proximal gastrectomy6 (4.3)
Smoking
 Never57 (40.7)
 Current29 (20.7)
 Ex-smoker54 (38.6)
Alcohol
 None69 (49.3)
 Social53 (37.9)
 Heavy*18 (12.9)
Atrophic gastritis
 Negative34 (24.3)
 Positive88 (62.9)
 Not applicable18 (12.9)
Intestinal metaplasia
 Negative38 (27.1)
 Positive102 (72.9)

Data are presented as mean±SD or number (%).

EGC, early gastric cancer; AGC, advanced gastric cancer.

*More than 200 g/wk.


Table 2 Postoperative Endoscopic Follow-Up Sessions

No. of follow-up timesNo. (%)
Up to 1st time96 (68.6)
Up to 2nd time19 (13.6)
Up to 3rd–7th time25 (17.9)

Mean period between surgery and the last endoscopic follow-up: 38.0±25.6 months.


Table 3 Comparison of Persistently Helicobacter pylori-Positive and -Negative Conversion Groups after Surgery (n=140)

VariableNegative conversion* (n=60)Persistently positive (n=80)p-value
Surgery0.261
 Subtotal B-I34 (56.7)57 (71.3)
 Subtotal B-II20 (33.3)18 (22.5)
 Subtotal Roux-en-Y2 (3.3)2 (2.5)
 Subtotal with jejunal interposition01 (1.3)
 Proximal gastrectomy4 (6.7)2 (2.5)
Age, yr58.95±11.0959.09±11.930.944
Male sex36 (60.0)49 (61.3)1.000
Smoking0.168
 Never22 (36.7)35 (43.8)
 Current17 (28.3)12 (15.0)
 Ex-smoker21 (35.0)33 (41.3)
Alcohol0.971
 None30 (50.5)39 (48.8)
 Social22 (36.7)31 (38.8)
 Heavy8 (13.3)10 (12.5)
Atrophic gastritis (baseline)0.677
 Negative16 (26.7)18 (22.5)
 Positive38 (63.3)50 (62.5)
 Inapplicable6 (10.0)12 (15.0)
Atrophic gastritis (1st follow-up)0.008
 Negative32 (53.3)36 (45.0)
 Positive8 (13.3)20 (25.0)
 Inapplicable20 (33.3)16 (20.0)
 Not available08 (10.0)
Intestinal metaplasia (baseline)0.340
 Negative19 (31.7)19 (23.8)
 Positive41 (68.3)61 (76.3)
Intestinal metaplasia (1st follow-up)0.001
 Negative38 (63.3)59 (73.8)
 Positive22 (36.7)13 (16.3)
 Not available08 (10.0)

Data are presented as number (%) or mean±SD.

*Spontaneous conversion to H. pylori-negative status at least once during follow-up period;

Statistically significant correlations (p<0.05).


References

  1. Pisani, P, Parkin, DM, Bray, F, and Ferlay, J (1999). Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer. 83, 18-29.
    Pubmed CrossRef
  2. Arnold, M, Moore, SP, Hassler, S, Ellison-Loschmann, L, Forman, D, and Bray, F (2014). The burden of stomach cancer in indigenous populations: a systematic review and global assessment. Gut. 63, 64-71.
    CrossRef
  3. Torre, LA, Bray, F, Siegel, RL, Ferlay, J, Lortet-Tieulent, J, and Jemal, A (2015). Global cancer statistics, 2012. CA Cancer J Clin. 65, 87-108.
    Pubmed CrossRef
  4. Plummer, M, Franceschi, S, Vignat, J, Forman, D, and de Martel, C (2015). Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer. 136, 487-490.
    CrossRef
  5. Fukase, K, Kato, M, and Kikuchi, S (2008). Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 372, 392-397.
    Pubmed CrossRef
  6. Fock, KM, Talley, N, and Moayyedi, P (2008). Asia-Pacific consensus guidelines on gastric cancer prevention. J Gastroenterol Hepatol. 23, 351-365.
    Pubmed CrossRef
  7. Bair, MJ, Wu, MS, and Chang, WH (2009). Spontaneous clearance of Helicobacter pylori colonization in patients with partial gastrectomy: correlates with operative procedures and duration after operation. J Formos Med Assoc. 108, 13-19.
    Pubmed CrossRef
  8. Abe, H, Murakami, K, and Satoh, S (2005). Influence of bile reflux and Helicobacter pylori infection on gastritis in the remnant gastric mucosa after distal gastrectomy. J Gastroenterol. 40, 563-569.
    Pubmed CrossRef
  9. Li, XB, Lu, H, Chen, HM, Chen, XY, and Ge, ZZ (2008). Role of bile reflux and Helicobacter pylori infection on inflammation of gastric remnant after distal gastrectomy. J Dig Dis. 9, 208-212.
    Pubmed CrossRef
  10. Johannesson, KA, Hammar, E, and Staël von Holstein, C (2003). Mucosal changes in the gastric remnant: long-term effects of bile reflux diversion and Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 15, 35-40.
    Pubmed CrossRef
  11. Suh, S, Nah, JC, and Uhm, MS (2012). Changes in prevalence of Helicobacter pylori infection after subtotal gastrectomy. Hepatogastroenterology. 59, 646-648.
    Pubmed
  12. Kim, SE, Park, YS, and Kim, N (2013). Effect of Helicobacter pylori eradication on functional dyspepsia. J Neurogastroenterol Motil. 19, 233-243.
    Pubmed KoreaMed CrossRef
  13. Kim, HJ, Hwang, SW, and Kim, N (2014). Helicobacter pylori and molecular markers as prognostic indicators for gastric cancer in Korea. J Cancer Prev. 19, 56-67.
    Pubmed KoreaMed CrossRef
  14. Dixon, MF, Genta, RM, Yardley, JH, and Correa, P (1996). Classification and grading of gastritis: the updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 20, 1161-1181.
    Pubmed CrossRef
  15. Rugge, M, Correa, P, and Dixon, MF (2002). Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading. Aliment Pharmacol Ther. 16, 1249-1259.
    Pubmed CrossRef
  16. Maehata, Y, Nakamura, S, and Fujisawa, K (2012). Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer. Gastrointest Endosc. 75, 39-46.
    CrossRef
  17. Shiota, S, Murakami, K, Fujioka, T, and Yamaoka, Y (2010). Population-based strategies for Helicobacter pylori-associated disease management: a Japanese perspective. Expert Rev Gastroenterol Hepatol. 4, 149-156.
    Pubmed KoreaMed CrossRef
  18. Fukuhara, K, Osugi, H, and Takada, N (2004). Duodenogastric reflux eradicates Helicobacter pylori after distal gastrectomy. Hepatogastroenterology. 51, 1548-1550.
    Pubmed
  19. Csendes, A, Smok, G, and Burgos, AM (2008). Behavior of the infection by Helicobacter pylori of the gastric remnant after subtotal gastrectomy and Roux-en-Y anastomosis for benign diseases. J Gastrointest Surg. 12, 1508-1511.
    Pubmed CrossRef
  20. Giuliani, A, Galati, G, Demoro, M, Scimò, M, Pecorella, I, and Basso, L (2010). Screening of Helicobacter pylori infection after gastrectomy for cancer or peptic ulcer: results of a cohort study. Arch Surg. 145, 962-967.
    Pubmed CrossRef
  21. Korstanje, A, van Eeden, S, and Offerhaus, GJ (2006). The 13carbon urea breath test for the diagnosis of Helicobacter pylori infection in subjects with atrophic gastritis: evaluation in a primary care setting. Aliment Pharmacol Ther. 24, 643-650.
    Pubmed CrossRef
  22. Onoda, N, Maeda, K, Sawada, T, Wakasa, K, Arakawa, T, and Chung, KH (2001). Prevalence of Helicobacter pylori infection in gastric remnant after distal gastrectomy for primary gastric cancer. Gastric Cancer. 4, 87-92.
    Pubmed CrossRef
  23. Kang, HY, Kim, N, and Park, YS (2006). Progression of atrophic gastritis and intestinal metaplasia drives Helicobacter pylori out of the gastric mucosa. Dig Dis Sci. 51, 2310-2315.
    Pubmed CrossRef
  24. Matsukura, N, Tajiri, T, and Kato, S (2003). Helicobacter pylori eradication therapy for the remnant stomach after gastrectomy. Gastric Cancer. 6, 100-107.
    Pubmed
  25. Rino, Y, Imada, T, and Shiozawa, M (2000). Helicobacter pylori of remnant stomach and optimal dose of amoxicillin for eradicating Helicobacter pylori. Hepatogastroenterology. 47, 567-570.
    Pubmed
  26. Kim, CG, Song, HJ, and Kook, MC (2008). Preoperative versus postoperative Helicobacter pylori eradication therapy in gastric cancer patients: a randomized trial. Am J Gastroenterol. 103, 48-54.
    CrossRef
  27. Sheu, BS, Yang, HB, and Wang, YL (2002). Stool antigen assay to screen H. pylori infection and to assess the success of 3-day and 7-day eradication therapy in the patients with partial gastrectomy. Helicobacter. 7, 199-204.
    Pubmed CrossRef
Gut and Liver

Vol.19 No.1
January, 2025

pISSN 1976-2283
eISSN 2005-1212

qrcode
qrcode

Share this article on :

  • line

Popular Keywords

Gut and LiverQR code Download
qr-code

Editorial Office