Gut and Liver 2017; 11(5): 635-641 https://doi.org/10.5009/gnl16397 Postoperative Helicobacter pylori Infection as a Prognostic Factor for Gastric Cancer Patients after Curative Resection
Author Information
Da Hyun Jung1, Yong Chan Lee2, Jie-Hyun Kim1, Hyunsoo Chung2, Jun Chul Park2, Sung Kwan Shin2, Sang Kil Lee2, Hyoung-il Kim3, Woo Jin Hyung3, and Sung Hoon Noh3
1Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea, 2Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, 3Department of Surgery, Yonsei University College of Medicine, Seoul, Korea

Yong Chan Lee, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea, Tel: +82-2-2228-1960, Fax: +82-2-362-6884, E-mail: leeyc@yuhs.ac
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

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

Few studies have evaluated the effect of Helicobacter pylori infection on the prognosis of patients diagnosed with gastric cancer (GC) after curative surgery. We investigated the association between the H. pylori infection status and clinical outcome after surgery.

Methods

We assessed the H. pylori status of 314 patients who underwent curative resection for GC. The H. pylori status was examined using a rapid urease test 2 months after resection. Patients were followed for 10 years after surgery.

Results

An H. pylori infection was observed in 128 of 314 patients. The median follow-up period was 93.5 months. A Kaplan-Meier analysis indicated that patients with H. pylori had a higher cumulative survival rate than those who were negative for H. pylori. Patients with stage II cancer who tested negative for H. pylori were associated with a poor outcome. In a multivariate analysis, H. pylori-negative status was a significant independent prognostic factor for poor overall survival.

Conclusions

Having a negative H. pylori infection status seems to indicate poor prognosis for patients with GC who have undergone curative resection. Further prospective controlled studies are needed to evaluate the mechanism by which H. pylori affects GC patients after curative surgery in Korea.

Keywords: Helicobacter pylori, Stomach neoplasms, General surgery, Prognosis
Abstract

Background/Aims

Few studies have evaluated the effect of Helicobacter pylori infection on the prognosis of patients diagnosed with gastric cancer (GC) after curative surgery. We investigated the association between the H. pylori infection status and clinical outcome after surgery.

Methods

We assessed the H. pylori status of 314 patients who underwent curative resection for GC. The H. pylori status was examined using a rapid urease test 2 months after resection. Patients were followed for 10 years after surgery.

Results

An H. pylori infection was observed in 128 of 314 patients. The median follow-up period was 93.5 months. A Kaplan-Meier analysis indicated that patients with H. pylori had a higher cumulative survival rate than those who were negative for H. pylori. Patients with stage II cancer who tested negative for H. pylori were associated with a poor outcome. In a multivariate analysis, H. pylori-negative status was a significant independent prognostic factor for poor overall survival.

Conclusions

Having a negative H. pylori infection status seems to indicate poor prognosis for patients with GC who have undergone curative resection. Further prospective controlled studies are needed to evaluate the mechanism by which H. pylori affects GC patients after curative surgery in Korea.

Keywords: Helicobacter pylori, Stomach neoplasms, General surgery, Prognosis
INTRODUCTION

In Korea, gastric cancer (GC) is the second most common cancer.1 Because GC is not a homogenous disease, the prognosis of patients with GC is diverse and is currently based on histology and tumor stage. Helicobacter pylori infection is closely associated with GC carcinogenesis. The International Agency for Research on Cancer, a subdivision of the World Health Organization (WHO), recognizes H. pylori as a group I carcinogen for gastric carcinoma.2 However, there are also GCs which are not related to H. pylori infection. H. pylori-negative GCs comprise 2% to 10% of all GCs.3 Previous studies suggest that a negative H. pylori status is correlated with more advanced disease than a positive H. pylori status.4,5 In addition, there are some reports that a negative H. pylori status is a prognostic factor of poor outcome in patients with GC after gastrectomy.68 Meimarakis et al.6 reported that relapse-free and overall survival of patients with positive H. pylori status are significantly higher than in patients with negative H. pylori status after curative resection. They evaluated the H. pylori status of 166 patients after curative resection to treat GCs. Among them, 41 patients (24.7%) were negative for H. pylori. And, they suggest that tumor-specific immune responses might be downregulated in patients who are negative for H. pylori.6 In Korea, there was a report that a negative H. pylori status is the most significant independent factor to predict poor prognosis in patients with locally advanced GC treated with adjuvant chemotherapy after curative surgery.8 Kang et al.8 investigated the H. pylori infection status in 274 locally advanced GC patients. Of these, 108 patients (39.4%) were negative for H. pylori. In this study, we aimed to investigate the H. pylori infection status and evaluate the clinical significance of H. pylori infection for patients with GC after they received curative surgery.

MATERIALS AND METHODS

1. Patients

Between February 1996 and December 2012, 314 patients were tested for H. pylori infection using a rapid urease test at least 2 months after curative resection to treat GC at Severance Hospital. Curative resection was defined according to the Japanese GC treatment guidelines.9 Patients were regarded as positive for H. pylori if they were positive by the rapid urease test. Patients were evaluated in terms of age, sex, history of chemotherapy or radiotherapy, and survival. The investigated variables also included tumor location, tumor size, depth of tumor invasion, lymph node metastasis, histological classification, lymphovascular invasion, and perineural invasion. The following patients were excluded: (1) patients that received a total gastrectomy; (2) patients who were not given the rapid urease test after gastrectomy; (3) patients with distant metastasis (M1); (4) patients that received chemotherapy prior to gastrectomy; and (5) patients who received H. pylori eradication therapy before curative resection. The pathologic stage of the tumor was determined according to the standards set by the seventh American Joint Committee on Cancer (AJCC).10 The Institutional Review Board of Severance Hospital approved this study.

2. Follow-up

During the first 2 years after gastrectomy, patients were assessed every 3 months by clinical examination, routine blood tests, and tumor markers; abdominal computed tomography and endoscopy were performed every 6 months. During the next 3 years, patients were examined every 6 months and received endoscopy every 12 months.

3. Statistical analysis

The chi-square and Fisher exact tests were used to compare the clinicopathological factors between groups based on their H. pylori status. The t-test was used for noncategorical variables in the intergroup comparisons of the clinicopathological characteristics. Results were considered significant if p<0.05. For the multivariate analysis, variables with p<0.05 on the univariate analysis and clinically important variables including age, gender, tumor size, and tumor stage were entered. The Kaplan-Meier method was used to determine the overall survival rates and the log-rank test was used to analyze differences in the survival curve. A Cox proportional hazards model and multivariate analyses were used to determine the risk assessment. All statistical analyses were performed using SPSS version 12.0 for Windows (SPSS Inc., Chicago, IL, USA).

RESULTS

1. Association among clinicopathological characteristics and H. pylori infection

Two hundred and ten men and 104 females were enrolled in this study. Their mean age was 55.4 years (standard deviation, ±11.5). There were no differences in age, gender, tumor size, tumor location, T stage, N stage, AJCC stage, WHO classification, Lauren classification, lymphovascular invasion, and perineural invasion between the H. pylori-positive and -negative groups (Table 1).

2. Association between overall survival and H. pylori infection status

The median duration for follow-up assessments was 93.5 months (range, 18 to 208 months). The 10-year overall survival rate was 95.3%, 96.5%, and 69.8% for stage I, II, and III cancers, respectively. In the univariate analysis, the 10-year overall survival rate was 95.1% and 91.5% for patients positive and negative for H. pylori, respectively (p=0.030) (Fig. 1). When examining the different stages of cancer, the overall survival rate for patients negative for H. pylori was lower than those who tested positive for H. pylori (Fig. 2). In the univariate analysis, old age and negative for H. pylori infection status were correlated with lower overall survival rate (Table 2). We performed subgroup analyses based on the different clinicopathological factors. Old age, lower third location, advanced T stage (T3/4), and negative for H. pylori infection status were correlated with poor overall survival rates (Table 3). In the multivariate analysis, old age (hazard ratio, 3.02; 95% confidence interval, 1.22 to 7.47; p=0.017) and negative H. pylori status (hazard ratio, 2.95; 95% confidence interval, 1.14 to 7.66, p=0.026) were independent prognostic factors of poor overall survival (Table 4).

3. Association between disease-specific survival and H. pylori status

We analyzed the disease-specific survival rates between H. pylori-negative and -positive GC patients. The 10-year disease-specific survival rates for patients with negative and positive H. pylori status were 93.9% and 95.5%, respectively (Fig. 3). In addition, we evaluated the disease-specific survival rates according to the T and N stages. For patients with T2–4 stages of disease, the disease-specific survival rate for patients with a negative H. pylori status was significantly lower than in those with a positive H. pylori status (Fig. 4).

DISCUSSION

According to Correa’s hypothesis, H. pylori infection is closely associated with the development of GC.11 However, there are few reports about the role of H. pylori infection in GC patients after curative surgical resection. Currently, there are no guidelines regarding the treatment of H. pylori infection after gastrectomy and the effects of treatment are unknown. To our knowledge, Lee et al.4 first reported that H. pylori seropositive GC patients showed a better prognosis after gastrectomy. There are two prospective studies that investigated the prognostic role of H. pylori infection.6,7 In Germany, Meimarakis et al.6 showed that a negative H. pylori status is an independent prognostic factor of poor relapse-free and overall survival in patients with GC after curative surgery. In patients with early-stage GC, the overall survival of patients who were positive for H. pylori was significantly higher than those who were negative.6 They evaluated H. pylori infection by bacterial culture, serologies, and histologies. Previous study reported that patients with a negative for H. pylori infection status have a worse prognosis after curative surgery. H. pylori infection was determined by polymerase chain reaction analysis for the vacA gene and a serology of H. pylori and CagA antibodies. H. pylori infection is correlated with long-term survival of patients with early as well as advanced pT disease.7 In this study, the 10-year overall survival of H. pylori-negative GC patients after curative resection was significantly lower than H. pylori-positive GC patients, which is similar to data observed in the previous studies. The prognostic impact of a negative for H. pylori infection status was significant for some of the subgroups such as old age, lower third location, and advanced T stage. In the multivariate analysis, old age and negative for H. pylori infection status were independent prognostic factors for poor overall survival of GC patients after curative surgery. We assessed H. pylori status using a rapid urease test 2 months after the curative surgery for GC.

The reason that negative for H. pylori infection status is correlated with poor prognosis in GC patients after curative surgery is not well known. There are several possible explanations. Immune responses caused by H. pylori could evoke antitumor immunity. A previous report shows that patients negative H. pylori status have more numbers of cells expressing OX40 in cancerous tissue than those positive H. pylori status. OX40 directly modulates immune suppression mediated by regulatory T cells.12 Thus, the authors contend that tumor-specific immune responses are downregulated in patients without H. pylori infection, in consequence of increased infiltration of OX40 positive cells.6 CD4+ and CD8+ T cells are increased in the presence of H. pylori, suggesting that tumor antigens might induce stronger immune reactions during H. pylori infection.13 Further, Xue et al.14 assume that H. pylori components either mimic or bind to specific receptors or surface molecules on gastric epithelial cells, which could result in autoantibodies. These autoantibodies could recognize GC cells which may display the mimic H. pylori antigens.14

A second plausible reason is the part of microsatellite instability (MSI) in H. pylori-positive GC. A previous study showed that patients with MSI are more likely to have active H. pylori infection than those with stable tumors.15 Further, previous study reported that alterations in MSI is associated with a higher rate of H. pylori infection, a better postoperative survival, and less lymph node metastasis.16 However, some authors argue whether H. pylori infection status has prognostic value or not. They suggest that negative for H. pylori infection status might be correlated with more advanced tumor status.5,17 In this study, there were no differences in the clinicopathological characteristics between the H. pylori-positive and -negative groups.

Our study has some limitations. First, this is a retrospective study and H. pylori infection was evaluated using a rapid urease test of the remnant stomach during the endoscopic examinations. Therefore, patients who underwent total gastrectomy because of proximally located GC were excluded from this study. And, we could not evaluate H. pylori infection by histology, urea breath test, and serology. Second, the 10-year overall survival of patients was 93.1%, which is quite high. This is mainly due to the high proportion of patients with stage I cancer (70.7%). To our knowledge, our study was the largest reported that analyzed the association between H. pylori infection and prognosis of GC patients who underwent curative surgery with long-term follow-up. In this study, patients negative for H. pylori infection were significantly associated with poor prognosis.

In conclusion, negative for H. pylori infection status appeared to be an indicator of poor prognosis in GC patients treated with curative surgery. Further prospective studies that include patients with advanced stages of cancer are needed to examine the effect of H. pylori status on the prognosis of GC patients after curative surgery.

Figures
Fig. 1. Effect of Helicobacter pylori status on overall survival of gastric cancer after gastrectomy.
Fig. 2. Effect of Helicobacter pylori status on overall survival of gastric cancer after gastrectomy according to American Joint Committee on Cancer stage. (A) Stage I, (B) stage II, and (C) stage III.
Fig. 3. Effect of Helicobacter pylori status on disease specific survival of gastric cancer after gastrectomy.
Fig. 4. Effect of Helicobacter pylori status on disease specific survival of gastric cancer after gastrectomy according to T and N stage. (A) T stage 2–4 and (B) N stage 1–3.
Tables

Association between Clinicopathologic Findings and Helicobacter pylori Status

VariableH. pylorip-value

Positive (n=128)Negative (n=186)
Age, yr54.4±10.856.2±12.00.174
Sex0.807
 Male87 (68.0)123 (66.1)
 Female41 (32.0)63 (33.9)
Tumor size, mm29.2±19.927.6±19.30.488
Tumor location1.000
 Middle third48 (37.5)71 (38.2)
 Lower third80 (62.5)115 (61.8)
T stage0.490
 T179 (61.7)130 (69.9)
 T219 (14.8)20 (10.8)
 T316 (12.5)20 (10.8)
 T414 (10.9)16 (8.6)
N stage0.526
 N091 (71.1)143 (76.9)
 N121 (16.4)20 (10.8)
 N210 (7.8)15 (8.1)
 N36 (4.7)8 (4.3)
AJCC stage0.346
 I86 (67.2)136 (73.1)
 II29 (22.7)30 (16.1)
 III13 (10.2)20 (10.8)
WHO classification0.992
 Well differentiated23 (18.0)35 (18.8)
 Moderately differentiated42 (32.8)64 (34.4)
 Poorly differentiated34 (26.6)46 (24.7)
 Signet ring cell26 (20.3)36 (19.4)
 Mucinous3 (2.3)5 (2.7)
Lauren classification0.321
 Intestinal63 (49.2)102 (54.8)
 Diffuse62 (48.4)76 (40.9)
 Mixed3 (2.3)8 (4.3)
Lymphovascular invasion0.268
 Absent112 (87.5)153 (82.3)
 Present16 (12.5)33 (17.7)
Perineural invasion0.842
 Absent116 (90.6)170 (91.4)
 Present12 (9.4)16 (8.6)

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

AJCC, American Joint Committee on Cancer; WHO, World Health Organization.

Univariate Analysis of Overall Survival

FactorNo. of patients10-Year OS rate, %HR (95% CI)p-value
Age, yr0.011
 ≤5616696.3Reference
 >5614889.23.21 (1.31–7.86)
Sex0.736
 Male21092.81.17 (0.48–2.83)
 Female10493.8Reference
Tumor size, mm0.081
 <2011098.4Reference
 ≥2020490.32.62 (0.89–7.69)
Tumor location0.068
 Middle third11987.7Reference
 Lower third19596.72.16 (0.94–4.92)
WHO classification0.882
 Well differentiated5893.5Reference
 Moderately differentiated10693.00.78 (0.25–2.47)
 Poorly differentiated8091.61.04 (0.33–3.28)
 Signet ring cell896.10.63 (0.15–2.63)
 Mucinous6287.51.77 (0.21–15.22)
H. pylori status0.036
 Positive18695.1Reference
 Negative12891.52.73 (1.07–6.98)
T stage0.132
 T1/220995.2Reference
 T3/410588.71.88 (0.83–4.28)
N stage0.315
 N023494.4Reference
 N1–38089.11.56 (0.66–3.71)

OS, overall survival; HR, hazard ratio; CI, confidence interval; WHO, World Health Organization; H. pylori, Helicobacter pylori.

Comparison of the Overall Survival and Hazard Ratios for Overall Survival Rate between Helicobacter pylori-Negative and H. pylori-Positive Gastric Cancer Patients according to Clinicopathologic Factors

Factor10-Year OS rate, %HR (95% CI)p-value

H. pylori-positiveH. pylori-negative
Age, yr
 ≤5696.696.11.33 (0.29–6.03)0.710
 >5693.186.43.88 (1.09–13.79)0.036
Sex
 Male94.191.62.28 (0.78–6.71)0.134
 Female97.091.64.73 (0.57–39.30)0.151
Tumor size, mm
 <2096.7100.03.21 (0.33–31.48)0.317
 ≥2094.486.82.68 (0.96–7.48)0.060
Tumor location
 Middle third89.786.41.47 (0.48–4.53)0.504
 Lower third98.895.09.60 (1.19–77.50)0.034
WHO classification
 Well differentiated95.292.13.29 (0.37–29.52)0.288
 Moderately differentiated92.493.32.28 (0.44–11.85)0.326
 Poorly differentiated94.089.12.23 (0.43–11.64)0.340
 Signet ring cell100.093.02.80 (0.22–35.81)0.428
 Mucinous100.080.042.98 (0.00–)0.661
T stage
 T1/294.995.61.90 (0.57–6.36)0.300
 T3/495.881.34.77 (1.02–22.28)0.047
N stage
 N095.593.82.52 (0.80–8.00)0.116
 N1–394.682.43.35 (0.67–16.84)0.142

OS, overall survival; HR, hazard ratio; CI, confidence interval; WHO, World Health Organization.

Multivariate Analysis of Overall Survival

FactorHR (95% CI)p-value
Age, yr0.017*
 ≤56Reference
 >563.02 (1.22–7.47)
Sex0.835
 Male1.10 (0.44–2.74)
 FemaleReference
Tumor size, mm0.236
 <20Reference
 ≥202.03 (0.63–6.57)
H. pylori status0.026*
 PositiveReference
 Negative2.95 (1.14–7.66)
T stage0.319
 T1Reference
 T2–41.68 (0.60–4.70)
N stage0.926
 N0Reference
 N1–31.05 (0.37–2.96)

HR, hazard ratio; CI, confidence interval; H. pylori, Helicobacter pylori.

*Variables with p<0.05;

Clinically important variables.

References
  1. Jung, KW, Won, YJ, and Oh, CM (2015). Prediction of cancer incidence and mortality in Korea, 2015. Cancer Res Treat. 47, 142-148.
    Pubmed KoreaMed CrossRef
  2. (1994). Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7–14 June 1994. IARC Monogr Eval Carcinog Risks Hum. 61, 1-241.
  3. Kato, S, Matsukura, N, and Tsukada, K (2007). Helicobacter pylori infection-negative gastric cancer in Japanese hospital patients: incidence and pathological characteristics. Cancer Sci. 98, 790-794.
    Pubmed CrossRef
  4. Lee, WJ, Lin, JT, and Shun, CT (1995). Comparison between resectable gastric adenocarcinomas seropositive and seronegative for Helicobacter pylori. Br J Surg. 82, 802-805.
    Pubmed CrossRef
  5. Hobsley, M, Tovey, FI, and Holton, J (2007). Helicobacter pylori and gastric cancer: neither friend nor foe. Gastroenterology. 132, 2076.
    Pubmed CrossRef
  6. Meimarakis, G, Winter, H, and Assmann, I (2006). Helicobacter pylori as a prognostic indicator after curative resection of gastric carcinoma: a prospective study. Lancet Oncol. 7, 211-222.
    Pubmed CrossRef
  7. Marrelli, D, Pedrazzani, C, and Berardi, A (2009). Negative Helicobacter pylori status is associated with poor prognosis in patients with gastric cancer. Cancer. 115, 2071-2080.
    Pubmed CrossRef
  8. Kang, SY, Han, JH, and Ahn, MS (2012). Helicobacter pylori infection as an independent prognostic factor for locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection. Int J Cancer. 130, 948-958.
    CrossRef
  9. Japanese Gastric Cancer Association (2011). Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 14, 113-123.
    Pubmed CrossRef
  10. Edge, SB, and Compton, CC (2010). The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17, 1471-1474.
    Pubmed CrossRef
  11. Correa, P (1988). A human model of gastric carcinogenesis. Cancer Res. 48, 3554-3560.
    Pubmed
  12. Takeda, I, Ine, S, and Killeen, N (2004). Distinct roles for the OX40-OX40 ligand interaction in regulatory and nonregulatory T cells. J Immunol. 172, 3580-3589.
    Pubmed CrossRef
  13. Bamford, KB, Fan, X, and Crowe, SE (1998). Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype. Gastroenterology. 114, 482-492.
    Pubmed CrossRef
  14. Xue, LJ, Su, QS, Yang, JH, and Lin, Y (2008). Autoimmune responses induced by Helicobacter pylori improve the prognosis of gastric carcinoma. Med Hypotheses. 70, 273-276.
    CrossRef
  15. Leung, WK, Kim, JJ, Kim, JG, Graham, DY, and Sepulveda, AR (2000). Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer. Am J Pathol. 156, 537-543.
    Pubmed KoreaMed CrossRef
  16. Wu, MS, Lee, CW, and Sheu, JC (2002). Alterations of BAT-26 identify a subset of gastric cancer with distinct clinicopathologic features and better postoperative prognosis. Hepatogastroenterology. 49, 285-289.
    Pubmed
  17. Rad, R, Prinz, C, and Schmid, RM (2006). Helicobacter pylori and prognosis of gastric carcinoma. Lancet Oncol. 7, 364-365.
    Pubmed CrossRef
Tables

Association between Clinicopathologic Findings and Helicobacter pylori Status

VariableH. pylorip-value

Positive (n=128)Negative (n=186)
Age, yr54.4±10.856.2±12.00.174
Sex0.807
 Male87 (68.0)123 (66.1)
 Female41 (32.0)63 (33.9)
Tumor size, mm29.2±19.927.6±19.30.488
Tumor location1.000
 Middle third48 (37.5)71 (38.2)
 Lower third80 (62.5)115 (61.8)
T stage0.490
 T179 (61.7)130 (69.9)
 T219 (14.8)20 (10.8)
 T316 (12.5)20 (10.8)
 T414 (10.9)16 (8.6)
N stage0.526
 N091 (71.1)143 (76.9)
 N121 (16.4)20 (10.8)
 N210 (7.8)15 (8.1)
 N36 (4.7)8 (4.3)
AJCC stage0.346
 I86 (67.2)136 (73.1)
 II29 (22.7)30 (16.1)
 III13 (10.2)20 (10.8)
WHO classification0.992
 Well differentiated23 (18.0)35 (18.8)
 Moderately differentiated42 (32.8)64 (34.4)
 Poorly differentiated34 (26.6)46 (24.7)
 Signet ring cell26 (20.3)36 (19.4)
 Mucinous3 (2.3)5 (2.7)
Lauren classification0.321
 Intestinal63 (49.2)102 (54.8)
 Diffuse62 (48.4)76 (40.9)
 Mixed3 (2.3)8 (4.3)
Lymphovascular invasion0.268
 Absent112 (87.5)153 (82.3)
 Present16 (12.5)33 (17.7)
Perineural invasion0.842
 Absent116 (90.6)170 (91.4)
 Present12 (9.4)16 (8.6)

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

AJCC, American Joint Committee on Cancer; WHO, World Health Organization.

Univariate Analysis of Overall Survival

FactorNo. of patients10-Year OS rate, %HR (95% CI)p-value
Age, yr0.011
 ≤5616696.3Reference
 >5614889.23.21 (1.31–7.86)
Sex0.736
 Male21092.81.17 (0.48–2.83)
 Female10493.8Reference
Tumor size, mm0.081
 <2011098.4Reference
 ≥2020490.32.62 (0.89–7.69)
Tumor location0.068
 Middle third11987.7Reference
 Lower third19596.72.16 (0.94–4.92)
WHO classification0.882
 Well differentiated5893.5Reference
 Moderately differentiated10693.00.78 (0.25–2.47)
 Poorly differentiated8091.61.04 (0.33–3.28)
 Signet ring cell896.10.63 (0.15–2.63)
 Mucinous6287.51.77 (0.21–15.22)
H. pylori status0.036
 Positive18695.1Reference
 Negative12891.52.73 (1.07–6.98)
T stage0.132
 T1/220995.2Reference
 T3/410588.71.88 (0.83–4.28)
N stage0.315
 N023494.4Reference
 N1–38089.11.56 (0.66–3.71)

OS, overall survival; HR, hazard ratio; CI, confidence interval; WHO, World Health Organization; H. pylori, Helicobacter pylori.

Comparison of the Overall Survival and Hazard Ratios for Overall Survival Rate between Helicobacter pylori-Negative and H. pylori-Positive Gastric Cancer Patients according to Clinicopathologic Factors

Factor10-Year OS rate, %HR (95% CI)p-value

H. pylori-positiveH. pylori-negative
Age, yr
 ≤5696.696.11.33 (0.29–6.03)0.710
 >5693.186.43.88 (1.09–13.79)0.036
Sex
 Male94.191.62.28 (0.78–6.71)0.134
 Female97.091.64.73 (0.57–39.30)0.151
Tumor size, mm
 <2096.7100.03.21 (0.33–31.48)0.317
 ≥2094.486.82.68 (0.96–7.48)0.060
Tumor location
 Middle third89.786.41.47 (0.48–4.53)0.504
 Lower third98.895.09.60 (1.19–77.50)0.034
WHO classification
 Well differentiated95.292.13.29 (0.37–29.52)0.288
 Moderately differentiated92.493.32.28 (0.44–11.85)0.326
 Poorly differentiated94.089.12.23 (0.43–11.64)0.340
 Signet ring cell100.093.02.80 (0.22–35.81)0.428
 Mucinous100.080.042.98 (0.00–)0.661
T stage
 T1/294.995.61.90 (0.57–6.36)0.300
 T3/495.881.34.77 (1.02–22.28)0.047
N stage
 N095.593.82.52 (0.80–8.00)0.116
 N1–394.682.43.35 (0.67–16.84)0.142

OS, overall survival; HR, hazard ratio; CI, confidence interval; WHO, World Health Organization.

Multivariate Analysis of Overall Survival

FactorHR (95% CI)p-value
Age, yr0.017*
 ≤56Reference
 >563.02 (1.22–7.47)
Sex0.835
 Male1.10 (0.44–2.74)
 FemaleReference
Tumor size, mm0.236
 <20Reference
 ≥202.03 (0.63–6.57)
H. pylori status0.026*
 PositiveReference
 Negative2.95 (1.14–7.66)
T stage0.319
 T1Reference
 T2–41.68 (0.60–4.70)
N stage0.926
 N0Reference
 N1–31.05 (0.37–2.96)

HR, hazard ratio; CI, confidence interval; H. pylori, Helicobacter pylori.

Variables with p<0.05;

Clinically important variables.

Figures
Fig. 1. Effect of Helicobacter pylori status on overall survival of gastric cancer after gastrectomy.
Fig. 2. Effect of Helicobacter pylori status on overall survival of gastric cancer after gastrectomy according to American Joint Committee on Cancer stage. (A) Stage I, (B) stage II, and (C) stage III.
Fig. 3. Effect of Helicobacter pylori status on disease specific survival of gastric cancer after gastrectomy.
Fig. 4. Effect of Helicobacter pylori status on disease specific survival of gastric cancer after gastrectomy according to T and N stage. (A) T stage 2–4 and (B) N stage 1–3.
Search for
Article
Archives