The purpose of this study is to investigate the recurrence rate of peptic ulcer disease (PUD) over a long follow-up period with PUD patients without
We retrospectively reviewed patients diagnosed with PUD on endoscopy and divided them into two groups: a
Total of nine hospitals in Korea participated, and a total of 1,761 patients were retrospectively reviewed. The HP-negative group included 553 patients, and the HP noneradicated group included 372 patients. The 5-year cumulative probabilities of PUD recurrence were 36.4% in the HP-negative group and 43.8% in the HP noneradicated group (p=0.113). The factors that were found to affect recurrence in the HP-negative group were elder, male, and comorbid chronic kidney disease.
The 5-year cumulative probability of PUD recurrence without
The purpose of this study is to investigate the recurrence rate of peptic ulcer disease (PUD) over a long follow-up period with PUD patients without
We retrospectively reviewed patients diagnosed with PUD on endoscopy and divided them into two groups: a
Total of nine hospitals in Korea participated, and a total of 1,761 patients were retrospectively reviewed. The HP-negative group included 553 patients, and the HP noneradicated group included 372 patients. The 5-year cumulative probabilities of PUD recurrence were 36.4% in the HP-negative group and 43.8% in the HP noneradicated group (p=0.113). The factors that were found to affect recurrence in the HP-negative group were elder, male, and comorbid chronic kidney disease.
The 5-year cumulative probability of PUD recurrence without
The most important cause of peptic ulcer disease (PUD) is
The recurrence rate of PUD with
Idiopathic peptic ulcer disease (IPUD) is defined by the presence of peptic ulcer without clear causes, such as
The 5-year cumulative recurrence rate of IPUD was reported to be 24.3% in recent study, and this result is significantly higher than those for NSAIDs-induced PUD and eradicated
We studied PUD recurrence in patients who were diagnosed PUD based on esophagogastroduodenoscopy (EGD) in 2005 and attended more than one follow-up visit. Total of nine hospitals in Korea participated, and a total of 1,761 patients were retrospectively reviewed. PUD was defined by the presence of an ulcer larger than 5 mm including all active-, healing-, and scar-stage tissue. We excluded 242 patients who were initially diagnosed with PUD and followed up with EGD earlier than 6 months after the initial diagnosis because it was unclear whether the disease was untreated or recurrent in these cases. We excluded 449 patients with histories of
Recurrent PUD was defined by the presence of an active-, healing-, or scar-stage ulcer in the stomach or duodenum 6 months after the initial diagnosis. The location, stage, number,
This study was approved by the Institutional Review Board at The Catholic University of Korea (SC10RCME0191).
The locations, stages, and numbers of PUDs were investigated. When a PUD was confirmed on EGD, we also determined the
The patients were divided into the following two groups: (1) a
The statistical analyses were conducted using SAS version 9.3 (SAS Institute, Cary, NC, USA). The baseline clinical characteristics of the patients and the analyses of ulcer recurrence are presented as descriptive data. The continuous variables of the two groups are presented as the means±the standard deviations and were tested with analyses of variance. The median values are presented for the variables that failed tests of normality, and the Kruskal-Wallis tests were applied to these variables. For the category-type variables, the ns (%) are presented, and chi-square and Fisher tests were applied. The cumulative probabilities of ulcer recurrence were estimated with the Kaplan-Meier method. The log-rank test was used to compare the time-to-event curves of the two groups. Cox-proportional hazards model analyses were conducted to investigate the relationships of the recurrence of
Among the 925 patients, 553 were included in the HP-negative group, and 372 were included in the HP noneradicated group (Table 1). The median age at the diagnosis of PUD of the HP-negative group was 58.5±13.7, which was greater than that of the noneradiated group (55.5±12.7, p<0.001). There were no differences between the two groups in terms of the other baseline characteristics.
The mean follow-up duration in the HP-negative group was 962 days, and the mean number of follow-up endoscopic procedures was 1.54 (Table 2). The mean follow-up duration in the HP noneradicated group was 1,028 days and the mean number of follow-up endoscopy procedures was 1.53.
The PUD patients were older because the HP-negative group was older in the baseline study. The rate of ulcer recurrence in the HP-negative group was 24.8%, which was significantly lower than that in the HP noneradicated group (p=0.040). The mean PUD recurrence duration in the HP-negative group was 518 days. Males accounted for more than 60% of both groups, and these proportions were higher than those of the baseline study.
In the HP-negative group, 24.8% of the patients experienced only one recurrence event, and 2.5% of the patients experienced more than two recurrence events. The most common stage of the recurrent ulcers was the healing stage (45.5%) followed by the active (29.5%) and scar stages (25%) with similar proportions. The location (i.e., stomach or duodenum) of the recurrent PUD was the same as the original ulcer in 67.9% of the patients, and the majority of recurrence events were single ulcers (81.7%).
The 5-year cumulative probabilities of PUD recurrence in the
Multivariate logistic regression analyses were performed to identify the factors that affected PUD without
As
This study retrospectively reviewed patients with PUD during 962 days, in average, up to 10 years to investigate the recurrence rate of PUD without
The location (i.e., stomach or duodenum) of the recurrent PUD was the same as the original ulcer in 67.9% of the patients. 83.9% of
As mentioned above, it is difficult to quantify the effect of other PUD risk factors. However, it is certain that risk factors other than
Age is an important factor in the occurrence and recurrence of PUD regardless of
In addition to age, the male sex and the presence of CKD are related to PUD recurrence. In Korea, although male was a risk factor of PUD development, it was not related recurrence.9 However, in this study, male was also a risk factor of recurrence in
In the present study, the other possible causes of
The most important causes of PUD without
Proton pump inhibitors are important drugs in the treatment of PUD, and the recurrence of PUD among NSAID-induced PUD patients who cannot stop taking NSAIDs can be reduced with proton pump inhibitors. In the present study, ulcer-protective drugs were investigated when recurrence occurred, but they were not found to affect the recurrence rate. We investigated whether the patients were taking such medicines, but the durations of medicine use were not accurately investigated. To investigate whether ulcer-protective drugs affect recurrence, the duration of the dosing period and the concomitant history of ulcer-aggravating drugs should be investigated.
The strengths of this study were that the total number of enrolled PUD patients without
The limitations of this research are the retrospective nature of the study and that endoscopic follow-ups were not performed. Endoscopic procedures were performed more frequently when symptoms were present, which might have affected the results. However, we overcame this limitation by including the scar-stage ulcers in the recurrence rate calculations. An additional shortcoming of this multicenter study is the fact that the diagnostic PUD criteria varied across the centers. The final limitation is that the durations of medicine use were unclear, which is a limitation in terms of the effects of ulcer-protective and aggravating drugs. Moreover, the recurrence rate of
In conclusion, the 5-year cumulative probability of PUD recurrence without
This work was supported by the Korean College of Helicobacter and Upper Gastrointestinal Research (grant Hp-2010.06).
No potential conflict of interest relevant to this article was reported.
Baseline Clinical Characteristics of the 925 Patients with Peptic Ulcer Disease
Characteristic | ?HP-negative? | ?HP noneradicated? | ?p-value? |
---|---|---|---|
Number | 553 | 372 | - |
Age, yr | 58.5±13.7 | 55.5±12.7 | <0.001 |
Male | 299 (54.1) | 222 (59.7) | 0.092 |
Ulcer location | 0.709 | ||
?Gastric ulcer | 345 (62.4) | 222 (59.7) | |
?Duodenal ulcer | 158 (28.6) | 114 (30.7) | |
?Gastric+duodenal | 50 (9) | 36 (9.7) | |
Ulcer stage | 0.017 | ||
?Active stage | 202 (36.5) | 116 (31.2) | |
?Healing stage | 199 (36.0) | 173 (46.5) | |
?Scar stage | 144 (26.0) | 78 (21.0) | |
?Multiple stage | 8 (1.4) | 5 (1.3) | |
No. of ulcer | 0.239 | ||
?Single | 486 (87.9) | 317 (85.2) | |
?Multiple | 67 (12.1) | 55 (14.8) | |
Smoking | 82 (14.9) | 68 (18.3) | 0.166 |
Alcohol | 117 (21.2) | 69 (18.6) | 0.325 |
Drug | |||
?NSAIDs | 28 (5.1) | 23 (6.2) | 0.465 |
?Aspirin | 55 (10.0) | 49 (13.2) | 0.128 |
?Antiplatelet | 19 (3.4) | 19 (5.1) | 0.209 |
?Steroid | 15 (2.7) | 4 (1.1) | 0.085 |
No. of comorbid disease? | 0.655 | ||
?0 | 369 (66.7) | 247 (66.4) | |
?1 | 147 (26.6) | 105 (28.2) | |
?≥2 | 37 (6.7) | 20 (5.4) |
Data are presented as number (%) or mean±SD.
HP,
Analysis of the Follow-up Data and Ulcer Recurrence of the Two Groups
HP-negative | ?HP noneradicated? | ?p-value? | |
---|---|---|---|
Duration of F/U, day* | 962 (400?1,620) | 1,028 (503?1,568) | 0.274?? |
Age of ulcer recurrence patient | 63.2±14.3 | 56.5±14.0 | <0.001?? |
Ulcer recurrence rate | 137 (24.8) | 115 (30.9) | 0.040?? |
No. of additional endoscopy during F/U | 1.54±0.76 | 1.53±0.76 | 0.813?? |
Sex (male) of ulcer recurrence patient | 82 (60.0) | 79 (68.7) | 0.146?? |
Duration of ulcer recurrence* | ?518 (310?1,091)? | 685 (366?1,259) | 0.238?? |
No. of ulcer recurrence | 0.097?? | ||
?0 | 416 (75.2) | 257 (69.1) | |
?1 | 123 (22.2) | 102 (27.4) | |
?2 | 10 (1.8) | 12 (3.2) | |
?3 | 4 (0.7) | 1 (0.3) | |
Ulcer stage at recurrence | 0.307?? | ||
?Active stage | 41 (29.9) | 36 (31.3) | |
?Healing stage | 62 (45.3) | 56 (48.7) | |
?Scar stage | 34 (24.8) | 21 (18.3) | |
?Multiple | 0 | 2 (1.7) | |
Gastric → gastric | 73 (53.3) | 61 (53) | 0.688?? |
Gastric → duodenal | 20 (14.6) | 14 (12.2) | |
Duodenal → duodenal | 20 (14.6) | 23 (20) | |
Duodenal → gastric | 14 (10.2) | 12 (10.4) | |
Multiple | 10 (7.3) | 5 (4.4) |
Data are presented as number (%) or mean±SD.
HP,
Multivariate Logistic Regression Analyses of the Risk Factors for Ulcer Recurrence in the Patients with
?Age adjusted HR (95% CI)? | ?p-value? | ?Multivariate HR (95% CI)? | ?p-value? | |
---|---|---|---|---|
Age, yr | 1.033 (1.018?1.047) | <0.001?? | 1.031 (1.017?1.046) | <0.001 |
Male sex | 1.627 (1.151?2.299) | 0.006?? | 1.519 (1.027?2.247) | 0.036 |
Smoking | 1.539 (0.988?2.396) | 0.057?? | 1.453 (0.885?2.385) | 0.140 |
Alcohol | 1.142 (0.755?1.728) | 0.530?? | - | - |
NSAIDs | 1.302 (0.655?2.590) | 0.452?? | - | - |
Aspirin | 0.943 (0.519?1.713) | 0.846?? | - | - |
Antiplatelet | 0.502 (0.159?1.587) | 0.241?? | - | - |
Anticoagulation | 2.355 (0.578?9.597) | 0.232?? | - | - |
Steroid | 1.711 (0.796?3.678) | 0.169?? | - | - |
No. of comorbid disease? | - | 0.468?? | - | - |
Cardiovascular | 1.154 (0.788?1.688) | 0.462?? | - | - |
Cerebrovascular | 0.733 (0.268?2.005) | 0.545?? | - | - |
Liver | 1.154 (0.668?1.992) | 0.608?? | - | - |
Renal | 2.057 (1.214?3.485) | 0.007?? | 2.026 (1.167?3.516) | 0.012 |
Pulmonary | 0.617 (0.225?1.69) | 0.348?? | - | - |
Antacids | 1.703 (1.187?2.444) | 0.004?? | 1.547 (0.988?2.422) | 0.057 |
H2 receptor antagonists | 1.461 (0.995?2.145) | 0.053?? | 1.297 (0.834?2.017) | 0.249 |
Proton pump inhibitors | 1.362 (0.95?1.954) | 0.093?? | 1.063 (0.694?1.63) | 0.778 |
Mucoprotective agent | 1.301 (0.892?1.897) | 0.172?? | - | - |
HR, hazard ratio; NSAIDs, nonsteroidal anti-inflammatory drugs.
Baseline Clinical Characteristics of the 925 Patients with Peptic Ulcer Disease
Characteristic | ?HP-negative? | ?HP noneradicated? | ?p-value? |
---|---|---|---|
Number | 553 | 372 | - |
Age, yr | 58.5±13.7 | 55.5±12.7 | <0.001 |
Male | 299 (54.1) | 222 (59.7) | 0.092 |
Ulcer location | 0.709 | ||
?Gastric ulcer | 345 (62.4) | 222 (59.7) | |
?Duodenal ulcer | 158 (28.6) | 114 (30.7) | |
?Gastric+duodenal | 50 (9) | 36 (9.7) | |
Ulcer stage | 0.017 | ||
?Active stage | 202 (36.5) | 116 (31.2) | |
?Healing stage | 199 (36.0) | 173 (46.5) | |
?Scar stage | 144 (26.0) | 78 (21.0) | |
?Multiple stage | 8 (1.4) | 5 (1.3) | |
No. of ulcer | 0.239 | ||
?Single | 486 (87.9) | 317 (85.2) | |
?Multiple | 67 (12.1) | 55 (14.8) | |
Smoking | 82 (14.9) | 68 (18.3) | 0.166 |
Alcohol | 117 (21.2) | 69 (18.6) | 0.325 |
Drug | |||
?NSAIDs | 28 (5.1) | 23 (6.2) | 0.465 |
?Aspirin | 55 (10.0) | 49 (13.2) | 0.128 |
?Antiplatelet | 19 (3.4) | 19 (5.1) | 0.209 |
?Steroid | 15 (2.7) | 4 (1.1) | 0.085 |
No. of comorbid disease? | 0.655 | ||
?0 | 369 (66.7) | 247 (66.4) | |
?1 | 147 (26.6) | 105 (28.2) | |
?≥2 | 37 (6.7) | 20 (5.4) |
Data are presented as number (%) or mean±SD.
HP,
Analysis of the Follow-up Data and Ulcer Recurrence of the Two Groups
HP-negative | ?HP noneradicated? | ?p-value? | |
---|---|---|---|
Duration of F/U, day* | 962 (400?1,620) | 1,028 (503?1,568) | 0.274?? |
Age of ulcer recurrence patient | 63.2±14.3 | 56.5±14.0 | <0.001?? |
Ulcer recurrence rate | 137 (24.8) | 115 (30.9) | 0.040?? |
No. of additional endoscopy during F/U | 1.54±0.76 | 1.53±0.76 | 0.813?? |
Sex (male) of ulcer recurrence patient | 82 (60.0) | 79 (68.7) | 0.146?? |
Duration of ulcer recurrence* | ?518 (310?1,091)? | 685 (366?1,259) | 0.238?? |
No. of ulcer recurrence | 0.097?? | ||
?0 | 416 (75.2) | 257 (69.1) | |
?1 | 123 (22.2) | 102 (27.4) | |
?2 | 10 (1.8) | 12 (3.2) | |
?3 | 4 (0.7) | 1 (0.3) | |
Ulcer stage at recurrence | 0.307?? | ||
?Active stage | 41 (29.9) | 36 (31.3) | |
?Healing stage | 62 (45.3) | 56 (48.7) | |
?Scar stage | 34 (24.8) | 21 (18.3) | |
?Multiple | 0 | 2 (1.7) | |
Gastric → gastric | 73 (53.3) | 61 (53) | 0.688?? |
Gastric → duodenal | 20 (14.6) | 14 (12.2) | |
Duodenal → duodenal | 20 (14.6) | 23 (20) | |
Duodenal → gastric | 14 (10.2) | 12 (10.4) | |
Multiple | 10 (7.3) | 5 (4.4) |
Data are presented as number (%) or mean±SD.
HP,
Data are presented as median.
Multivariate Logistic Regression Analyses of the Risk Factors for Ulcer Recurrence in the Patients with
?Age adjusted HR (95% CI)? | ?p-value? | ?Multivariate HR (95% CI)? | ?p-value? | |
---|---|---|---|---|
Age, yr | 1.033 (1.018?1.047) | <0.001?? | 1.031 (1.017?1.046) | <0.001 |
Male sex | 1.627 (1.151?2.299) | 0.006?? | 1.519 (1.027?2.247) | 0.036 |
Smoking | 1.539 (0.988?2.396) | 0.057?? | 1.453 (0.885?2.385) | 0.140 |
Alcohol | 1.142 (0.755?1.728) | 0.530?? | - | - |
NSAIDs | 1.302 (0.655?2.590) | 0.452?? | - | - |
Aspirin | 0.943 (0.519?1.713) | 0.846?? | - | - |
Antiplatelet | 0.502 (0.159?1.587) | 0.241?? | - | - |
Anticoagulation | 2.355 (0.578?9.597) | 0.232?? | - | - |
Steroid | 1.711 (0.796?3.678) | 0.169?? | - | - |
No. of comorbid disease? | - | 0.468?? | - | - |
Cardiovascular | 1.154 (0.788?1.688) | 0.462?? | - | - |
Cerebrovascular | 0.733 (0.268?2.005) | 0.545?? | - | - |
Liver | 1.154 (0.668?1.992) | 0.608?? | - | - |
Renal | 2.057 (1.214?3.485) | 0.007?? | 2.026 (1.167?3.516) | 0.012 |
Pulmonary | 0.617 (0.225?1.69) | 0.348?? | - | - |
Antacids | 1.703 (1.187?2.444) | 0.004?? | 1.547 (0.988?2.422) | 0.057 |
H2 receptor antagonists | 1.461 (0.995?2.145) | 0.053?? | 1.297 (0.834?2.017) | 0.249 |
Proton pump inhibitors | 1.362 (0.95?1.954) | 0.093?? | 1.063 (0.694?1.63) | 0.778 |
Mucoprotective agent | 1.301 (0.892?1.897) | 0.172?? | - | - |
HR, hazard ratio; NSAIDs, nonsteroidal anti-inflammatory drugs.