THE AUEWXN JOURNAL OF GASTROENTEROLCGY Copyright 0 1998 by Am. Cell. of Gastroenterology Published by Elsevier Science Inc.

Vol. 93, No. 3, 1998 ISSN OOtX-9270/98/$19.00

PII SooO2-9270(97)00096-8

Original contributions

Peptic Ulcers After the Hanshin-Awaji Earthquake: Increased Incidence of Bleeding Gastric Ulcers

Nobuo Aoyama, M.D., Yosbikazu Kinoshita, M.D., Sotaro Fujimoto, M.D., Seiichi Hiieno, M.D,,, Akio Todo, M.D., Masato Kasuga, M.D., and Tsutomu Chiba, M.D.

Second and Fourth Departments of Internal Medicine, Kobe University School of Medicine and Hyogo Gastroen ferology Study Group, Kobe, and Division of Gastroenterology and Hepatology, Department of Internal Medicine, Postgraduate School of Medicine,

Kyoto University, Kyoto, Japan

Objective: Although physical stresses are known to induce peptic ulcers in the upper gastrointestinal tract, it remains controversial whether emotional stress can cause peptic ulcers. Therefore, we examined retrospec- tively the influence of the Hanshin-Awaji earthquake that occurred in Japan in January 1995 on the occur- rence of peptic ulcer disease among noninjured resi- dents. Methods: Sixty-one hospitals, covering 70% of all endoscopy examinations performed in this area, joined the study and were divided into three areas according to the severity of the damage. A comparison was made between a group of 10,831 patients who underwent up- per gastrointestinal endoscopy within 2 months after the earthquake and 16,100 who did so in the same hospitals during the corresponding period in 1994. Results: In the most devastated area, in spite of a dramatic decrease in the total number of endoscopies (50.0%), patients with gastric ulcer (GU) were increased in 1995, whereas those with duodenal ulcer were decreased, resulting in a higher ratio of gastric to duodenal ulcers than in 1994 (3.07 vs 1.88). In particular, there was a marked increase in bleeding GU. The mean age of patients with GU was significantly higher in 1995 than in 1994. Conclusion: The Hanshin-Awaji earthquake-induced life event stress not only triggered but also exacerbated GU, particularly in the elderly. (Am J Gastroenterol1998;93:311-316.0 1998 by Am. Coll. of Gastroenterology)

INTRODUCTION

Serious physical stresses such as trauma (l-4) and burns (1, 2, 5) induce peptic ulcer disease of the upper gastroin- testinal tract. However, conflicting data are available on the development of peptic ulcer disease in states of emotional stress such as tension and anxiety (6-10).

Received June IO, 1997; accepted Oct. 20, 1997.

In the early morning of January 17, 1995, the Hanshin- Awaji district, in the southern part cf Hyogo prefecture, Japan, was hit by the most devastating earthquake since the 1923 Tokyo earthquake, measuring 7.2 on the Richter scale. More than 6,000 people were killed, and more than 25,000 injured. Furthermore, during the months after the earth- quake, more than 3 10,000 people bet ame at least tempo- rarily homeless, and the normal course of their daily life was completely altered, causing great tension and anxiety. Within a few days following the earthquake, we became aware of a significant increase in patients with bleeding ulcers in the upper gastrointestinal tract. Thus, it may be considered that the development of the ulcers on this occa- sion was related to tension and/or anxiety.

In the present study, therefore, we examined the influence of life event stress due to the Hanshin-Awaji earthquake on the incidence of peptic ulcers of the upper gastrointestinal tract among noninjured residents in this district, and com- pared their characteristics with those of similar patients seen during the corresponding period in the previous year. For this purpose, 61 major hospitals in thit; district, covering as many as 70% of all upper gastrointest:.nal endoscopy cases in Hyogo prefecture, collaborated.

MATERIALS AND METHODS

Sixty-one major hospitals, covering as many as 70% of all upper gastrointestinal endoscopy cases seen in Hyogo pre- fecture, participated in this study. The records of all the patients who underwent upper gastrointestinal endoscopy within the 8 wk after the Hanshin-Awaji earthquake in 1995 because of various abdominal symptoms were examined. The records of all the upper gastrointestinal endoscopy patients during the corresponding pe;iod of the previous year (between January 17 and March 13, 1994) in the same hospitals were used as controls. To evaluate the degree of stress objectively, we divided the 61 hospitals into 3 groups according to the severity of the earthquake in the areas

311

312 AOYAMA et al.

A

AJG -- Vol. 93, No. 3, 1998

Hyogo prefecture {

B

(%I

80-

60-

-O- Area I -t- Area II

+ Area III

0-m 0 l-2 3-4 !j-6 7-8

weeks after the earthquake

FIG. 1. (A) A map of Hyogo prefecture, the region stricken by the Hanshin-Awaji earthquake in 1995. The region was divided into three areas according to the severity of the damage. Area 1 = the region most severely affected; area 2 = the region surrounding area 1; and area 3 = the relatively spared region. The thick solid line shows the boundary of Kobe city. (B) Number of endoscopies performed during the 8 weeks following the earthquake. Data are shown as percentages of the number of endoscopies performed during the corresponding period in 1994 in the same area.

TABLE 1

Numbers of Endoscopies Performed and Numbers of Patients With Gastric fGU) and Duodenal fflcers (DU) in the Three Dlfferent Areas During the Corresponding Periods (Jan 17 to Mar 13) in 1994 and 1995

No. of Endoscopies

1994 1995

GU DU GU + DU -

1994 1995 1994 1995 1994 1995

Area I

Area 2

Area 3

Total

6,065 3,030* 297 335* 158 109* IO 10 (50.0) (112.4) (69.0) (100.0)

6,012 4,089 292 323 153 126 9 8 (68.0) (110.6) (82.4) (88.9)

4,023 3,712 320 302 154 123 7 8

(92.3) (94.4) (79.9) (I 14.3) 16,100 IO.83 1 909 960 465 358 :!6 26

(67.3) (105.6) (77.0) (100.0)

Values in parentheses show percentages of respective values in 1994. * Significantly different from 1994 @ < 0.01). as determined by ,$ analysis.

where they were located: 1) 23 hospitals located at the of

AJG - March 1998

ihx he u&v iu order tu exclude mvolvement 02 p~vi~e~ sass in at tGe&Jpm~ of pqY&c VkTS wxei elc et&l- qdne. In a&Y&n to ani&+n$ tine incXrence ~5 pepix ulcers, we checked the hospital records for each case of peptic ulcer that occurred after the earthquake. These data included patient age and sex, whether the ulcer was com- plicated by bleeding, whether there was a history of peptic ulcer, and whether there was a history of nonsteroidal an- tiinflammatory drugs (NSAIDs) used after the earthquake in 1995 or during the 4 wk before the diagnosis in 1994, and these data were compared with those obtained in 1994. furthermore, we tested the sera from the patients with peptic ulcers developed aFter the earthquake for the presence of the Helicobacter pylori (H. pylori) IgG antibody. We selected the patients whose serum was sampled at or just after the diagnosis of ulcers.

PEPTIC ULCERS AFTER EARTHQUAKE

RESULTS

Number of endoscopy cases (Fig. 1B)

Area 1 35 100 (2.86) 8 19 (2.38) Area 2 28 58 (2.07) 14 17 (1.21)

Area 3 20 22 (1.10) 7 6 (0.86)

Values in parentheses show 19950994 ratios.

In area 1, 256 endoscopies were carried out during the first 2 wk after the earthquake. This was only 15.9% of the total number of endoscopies performed in the corresponding period of 1994 at the same hospitals. This dramatic decrease in endoscopies appeared to be due not only to the loss of function of the hospitals but also to the difficulty experi- enced by the patients in gaining access to the hospitals. Within 8 wk after the earthquake, the number of endosco- pies performed in area 1 was only 50% of that in 1994 (Table 1). In area 2, on the other hand, the number of endoscopies in 1994 was 68% of that in 1995, and in area 3, the number was 92.3% of that in 1995 (Table 1). These data indicated that our division of the three areas corresponded well to the severity of the earthquake (Fig. 1A).

Incidence of peptic ulcers with bleeding

In area 1, the number of incidences of bleeding in both GU and DU cases increased markedly after the earthquake compared with those in 1994 (Table 3). ,Surprisingly, for the first 2 wk after the earthquake in area I, 46.8% and 36.4% of GU and DU cases, respectively, showed bleeding, com- pared with only 10.7% and 2.9%, respectively, in 1994 (Fig. 2). In agreement with these data, the number of patients who received blood transfusions during these 8 wk was signifi- cantly higher in 1995 than in 1994 in area 1 (63 vs 9). The number of bleeding GU cases was also increased in area 2 in 1995. In contrast, there was no difference in the number of bleeding GU cases in area 3 and those of bleeding DU in area 2 or 3 between 1995 and 1994 (Table 3).

Incidence of peptic ulcers In area 1, 335 cases of gastric ulcer (GU) and 109 cases

of duodenal ulcer (DU) were diagnosed during the 8 wk in 1995. In addition, 10 patients had both GU and DU. Al- though the total number of endoscopies was significantly lower than that in the same period in 1994, the number of GU cases in 1995 was higher (Table 1). Indeed, 18.4% of all of the endoscopy cases in the 2 wk immediately following the earthquake were GU in area 1 (4.7% in 1994). In contrast, in accordance with the decrease in the number of endoscopies performed, the number of DU cases in 1995 was slightly lower than that in 1994 in area 1 (Table 1). The number of the patients who had both GU and DU was the same between 1994 and 1995. Similar to area 1, the number of GU cases was also slightly increased in 1995 in area 2. However, there was no increase in the number of GU cases in area 3, or in that of DU cases or GU + DU cases in areas 2 and 3 during the 8 wk after the earthquake (Table 1).

Characteristics of the patients with peptic ulcers in area 1 (Table 4)

There were more male than female patients with GU as well as with DU both in 1994 and 1995 in area 1, and there was no difference in the male/female ratio of the patients with GU between 1994 and 1995, whereas the male/female ratio of DU patients was slightly higher in 1995 than in 1994. The percentage of recurrent GU in 1995 was slightly lower than in 1994, although there was no difference in patients with recurrent DU between 1995 and 1994. On the other hand, the percentage of the patients who received NSAIDs administration after the earthquake in 1995 was not different from that of the patients who had a history of NSAIDs intake immediately before the diagnosis in 1994 both in GU and DU. Moreover, percentage of the patients who received NSAIDs administration after the earthquake in area 1 was not different from that in area 2 or 3 (data not shown).

The GU/DU ratios in all three areas in 1995 were higher One remarkable finding was that the patients with GU in than their respective values in 1994; the difference was most 1995 were significantly older than those in 1994 (p < O.Ol), prominent in area 1 (Table 2). whereas no difference was found in patients with DU be-

1994 1995

Area 1 1.88 3.07 Area 2 1.91 2.56

Area 3 2.08 2.46

TABLE 3 Comparison of the Numbers of Peptic Ulcers Wiih Bleeding in the Three

Areas Developed During the Corresponding Penods (Jan I7 to Mar 13) in 1994 and Z99S

GU DU -

1994 1995 1994 1995

314 AOYAMA et al. AJG - Vol. 93, No. 3, I998

(o/g) GU 50-

40-

20- &

30-

lo- o

OO - 7-8

(%I DU

0 1-2 3-4 5-6

weeks after the earthquake FIG. 2. Bleeding peptic ulcers that occurred in area 1 within 8 weeks after the Hanshin-Awaji earthquake. Data are expressel as percentages of the total

number of GU (left-panel) and DU (right panel) cases, respectively.

TABLE 4

Characteristics of Patients With Peptic Ulcers that Developed Within

the 8 wk After the Hanshin-Awaji Earthquake in Area I

GU DU

1994 1995 1994 1995

Male/female ratio 1 .I5 1.87 1.43 2.00

Recurrent ulcers (%) 31.5 21.9 45.1 45.1

History of NSAIDs 5.4 4.8 3.8 3.1

use (%)

Age (yr)* 53.2 2 4.2 63.6 t 5.5t 52.3 2 4.9 52.5 2 4.8

* Patient age given as mean + SE. i Significantly different from respective value in 1994 (p < 0.01) as

determined by nonpaired Students t test.

tween the 2 years (Fig. 3). Reflecting those data, the GU/DU ratio for elderly patients was higher in 1995 than in 1994 (Fig. 4). Thus, the higher GU/DU ratio in 1995 in area 1, as shown in Table 2, appeared to be due mainly to the higher GU/DU ratio for elderly patients.

Seroprevalence of H. pylori infection (Table 5)

Seroprevalence of H. pylori infection in patients with GU and those with DU, which developed after the earthquake, were 8 1.8% and 86.8%, respectively, in the most devastated area (area l), and those were not different from respective values in area 2 or 3.

DISCUSSION

It is well established that various physical stresses such as trauma and bums can induce peptic ulcers of the upper gastrointestinal tract (l-5). On the other hand, conflicting data are available concerning the role of emotional stress or psychosomatic factors in the development of peptic ulcers (6-l 1). Ganam et al. (6) found no increase of upper gas- trointestinal bleeding during the Gulf War in residents in

Hadera, located in Israels central coastal region. In contrast, the incidence of perforated peptic mcers was increased in London during the German bombing of World War II (10). In contrast to physical stresses, however, it appears difficult to evaluate the severity of emotional stress objectively, and this may be the reason why general agreement has not yet been reached. Indeed, it is possible that the severity of tension or fear may not have been sufficient to cause peptic ulcers or bleeding in Hadera during the Gulf War, inasmuch as it was not a direct missile target 1:6). In this regard, the Hanshin-Awaji earthquake provides an opportunity to ex- amine the effect of serious mental stress caused by an undisputedly devastating event on the occurrence of peptic ulcer disease of the upper gastrointestinal tract. Moreover, to overcome the difficulty in scoring the degree of emotional stress, we divided the area stricken by the Hanshin-Awaji earthquake into three zones according to the severity of devastation and compared the occurrence of peptic ulcers among them. In addition, because endoscopy examination is performed very widely in Japan, we were able to accumulate a large number of endoscopy cases, thus allowing more objective analysis of data than any previous reports.

In spite of the dramatic decrease in the number of endos- copies performed, the number of patients with GU was increased whereas that of patients with DU was slightly decreased particularly in area 1, where the devastation was most severe. It might be pointed out that the difference between 1994 and 1995 was not as clear as expected even in area 1. However, it should be emphasized that it was ex- tremely difficult for the physicians to perform endoscopy and for the patients to gain access to the hospital after the earthquake, and that endoscopies for patients with mild symptoms appeared to be postponed. Thus, considering the 50% decrease in the total number of ertdoscopies performed, it is strongly suspected that the actual number of GU pa-

GU DU

PEPTIC ULCERS AFTER EARTHQUAKE 315 AJG - March 1998

60 20

lllJl+4

15

10

5

0 3-59-60-69-70-79 60-

01994

W19ES

h, -19 20-29 30-39 40-49 60-59 60-69 70-79 60.

Age FIG. 3. Age distribution of patients who developed peptic ulcers during the 8 weeks after the Hanshin-Awaji earthquake in 1995. The data are compared

to those in 1994.

.$ 6-

E 5-

a 4-

3 3-

2-

l-

( 1 1 U

J I

0 -;9 2&9 30139 40149 659 60169 70179 6b-

1994 1995

FIG. 4. GUiDU ratio for peptic ulcers that developed during the 8 weeks after the Hanshin-Awaji earthquake in various age groups. The data for 1995 (u) are compared with those for 1994 (M).

TABLE 5

Prevalence of H. pylori IgG Antibody in Serum of Peptic Ulcer Patients Ajier the Earthquake

GU DU

Area 1 99/121 (81.8) 33/38 (86.8)

Area2 117/153 (76.5) 42/49 (85.7) Area3 140/182 (76.9) 57/68 (83.8)

Values represent the number of patients (patients with positive anti-H. pyiori IgG/totaJ patients whose serum were tested). Values in parentheses show percentages of the total number of patients tested in each group.

tients would have been further increased after the earth- quake. The fact that the percentage of GU patients in the total number of those who received endoscopy was dramat- ically increased in the most devastated area may further support this possibility. Likewise, it may also be reasonable to consider that the actual number of DU patients would not have been so different between 1994 and 1995. The fact that

the GWDU ratio was increased after the earthquake, most prominently in area 1, may further support the notion that earthquake stress predominantly increased the incidence of GU. It is not clear why the earthquake stress increased the incidence of GU primarily. It may be considered that in- creased use of NSAIDs after the earthquake has been partly responsible. Indeed, NSAIDs are known to induce GU more frequently than DU (12, 13). However, this is unlikely because the percentage of the patients who received NSAIDs administration did not increase after the earthquake in the most devastated area. In contrast, it may be difficult to rule out a possibility that poor nutrition occuring after the earthquake was involved in the development of peptic ul- cers. On the other hand, one noteworthy finding is that the mean age of the patients that developed GU after the earth- quake was significantly older than in the corresponding period in 1994, whereas the mean age of DU patients was not different, resulting in the increased GU/DU ratio par- ticularly for older patients in 1995. Thus, it is clear that the increase in the number of GU patients after the earthquake was mainly attributable to the increase in elderly patients. In this regard, it should be emphasized that GU/DU ratio increases with age in Japan (14), and this appears to be correlated with the progression of gastric mucosal atrophy, which disturbs the defense mechanism of the gastric mucosa (15, 16). Considering this background of gastric mucosa in the Japanese elderly, it may be reasonable to conclude that, in older persons, emotional stress can be more of a risk factor for GU than DU. The fact that aging is associated with a decline in gastric mucosal prostaglandins may further support this idea (17).

Another important finding in this study was the signifi- cant increase of bleeding in both GU and DU cases partic- ularly in area 1. Reflecting this finding, patients who re- ceived transfusion were seven times more numerous in 1995 than in 1994 in area 1. These data are in agreement with several previous reports indicating that emotional stress

316 AOYAMA et al.

increases the risk of life threatening complications of peptic ulcer such as hemorrhage and perforation (10, 18). It is noteworthy that the increase in the number of bleeding ulcers was more evident than that of the total number of peptic ulcers in this study. However, this is perhaps not surprising, because all the patients with bleeding symptoms would have come to the hospital even after the earthquake. In any event, the data clearly indicate that although the earthquake stress increased the incidence of GU predomi- nantly, it exacerbated the severity of both GU and DU.

There were always more male patients than female pa- tients with both GU and DU in any of the areas in this study, a feature that agrees with many previous reports (14, 19, 20). Moreover, the male/female ratio for GU patients after the earthquake was not different from that in the previous year. Thus, emotional stress may not be a factor influencing male predominance in GU.

The present study also revealed a decreased percentage of recurrent GU after the earthquake. Recently, it has been suggested that, except for those who are receiving NSAIDs, most patients with recurrent peptic ulcer are infected with H. pylori (21, 22). Thus, whether or not the decrease in the percentage of recurrent GU after the earthquake was related to the difference in the rate of infection with H. pylori is an interesting question.

It is generally believed that H. pylori infection and the use of NSAIDs are the major independent risk factors for peptic ulcers of the upper gastrointestinal tract, and that these two factors can explain the majority of cases of the peptic ulcer disease (23). However, it still remains unknown whether mental stress can be an independent risk factor for peptic ulcers. In the present study, we could not find a causal relationship between NSAIDs intake and the development of peptic ulcers after the earthquake. In contrast, we found that seroprevalence of H. pylori infection in the patients with peptic ulcers that developed after the earthquake in the most devastated area was as high as those in nondevastated areas. Moreover, it was similar to or even higher than that reported previously in peptic ulcer cases in Japan that were unrelated to the earthquake (24, 25). These data may indi- cate that H. pylori infection played some role in the devel- opment of peptic ulcers under the stressful conditions caused by the Hanshin-Awaji earthquake.

In summary, our data suggest that the Hanshin-Awaji earthquake-induced stress triggered and aggravated GU, particularly in the elderly. Although it is of course difficult to predict occurrence of natural disasters like the Hanshin- Awaji earthquake, prophylactic administration of antiulcer drugs may be advisable, particularly for those who have a history of peptic ulcer disease.

ACKNOWLEDGMENTS

We are grateful to the members of the Hyogo Gastroen- terology Study Group, including 61 major hospitals in Hyogo prefecture, Japan, for participating in the study.

AJG - Vol. 93, No. 3, 1998

This study was supported in part by a grant from the Ministry of Health and Welfare, and the Ministry of Edu- cation, Science and Culture, Japan.

Reprint requests and correspondence: Prof. Tsutomu Chiba, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Post- graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan

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