Yonago Acta medica 2012;55:57–61

Clinicopathologic Characteristics and Prognosis of Gastric
Cancer in Young Patients
Hiroaki Saito, Seigo Takaya, Yoji Fukumoto, Tomohiro Osaki, Shigeru Tatebe andMasahide Ikeguchi
Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, JapanTo determine the clinicopathologic characteristics and prognosis of gastric cancer in young
patients, a total of 1985 gastric cancer patients who had undergone gastrectomy at our hospital were reviewed. The male-to-female ratio was significantly lower in the young patients thanin either the middle-aged (P < 0.0001) or elderly patients (P < 0.0001). Undifferentiated carcinoma was observed more frequently in the young patients compared with either the middleaged (P < 0.0001) or elderly patients (P < 0.0001). Furthermore, peritoneal metastasis wasobserved more frequently in the young patients than in either the middle-aged (P < 0.005) or
elderly patients (P < 0.005). Five-year survival rates were 61.0, 73.6 and 68.1% in the young,middle-aged and elderly patients, respectively. The prognosis of the middle-aged patients was
significantly better than that of either the young or the elderly patients (P < 0.05). Multivariate analysis indicated that age was an independent prognostic factor. Peritoneal recurrence
was more frequently observed in the young patients than either the middle-aged or the elderly
patients (P < 0.05). Gastric cancer in young patients has unique characteristics, namely, a
predominance of female patients and a high frequency of undifferentiated cancer and peritoneal metastasis and recurrence.
Key words: age; gastric cancer; prognosis
Gastric cancer is frequent in middle-aged andelderly populations. Although gastric cancer israre in young populations (Okamoto et al., 1988;
Mitsudomi et al., 1989), it has been reported that
gastric cancer in young patients has some uniquecharacteristics compared with that in middleaged and elderly patients. For instance, the maleto-female ratio shows a predominance of females
among younger patients (Bloss et al., 1980; Moriet al., 1985; Sandler and Holland, 1987; Tso et al.,1987). Furthermore, a significantly higher frequency of both Borrmann type 4 and poorly differentiated adenocarcinoma with a scirrhus growth
pattern has been noted as a characteristic of gastriccancer in young patients (Bloss et al., 1980; Sandler
and Holland, 1987; Tso et al., 1987; Okamoto et al.,

1988; Mitsudomi et al., 1989). On the other hand,the prognosis of gastric cancer in young patients remains unclear thus far. The aim of the present study
was to clarify the clinicopathologic characteristics
and prognosis of gastric cancer in young patients.
Materials and MethodsPatients
The present study was based on a retrospective analysis of 1985 patients with gastric adenocarcinoma
who underwent gastrectomy at our institution between January 1975 and December 2000. The clinicopathologic findings were determined according
to the Japanese Classification of Gastric Carcinoma
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Table 1. Correlation between age and clinicopathologic features
Variables				Young [84]GenderHistology§
Tumor size
Serosal invasion
Lymph node metastasis
Lymphatic involvement
Vascular involvement
Peritoneal metastasis
Liver metastasis
Stage
Lymph node dissection||Multiple gastric cancer
Curability

Male
FemaleDifferentiatedUndifferentiated< 8 cm≥ 8 cm
AbsentPresent
AbsentPresent
AbsentPresent
AbsentPresent
AbsentPresent
AbsentPresent
I/II
III/IV
D0/D1
D2/D3
AbsentPresent
Curative
Non-curative

32 (38.1)***, †††52 (61.9)
10 (11.9)***, †††74 (88.1)
53 (63.1)*
31 (36.9)
49 (58.3)
35 (41.7)
46 (54.8)
38 (45.2)
39 (46.4)
45 (53.6)
61 (72.6)†
23 (27.4)
73 (86.9)††
11 (13.1)
84 (100)0 (0)52 (61.9)
32 (38.1)
8 (9.5)††76 (90.5)
82 (97.6)
2 (2.4)74 (88.1)
10 (11.9)

Age classification
Middle-aged [1314]
871 (66.3)
443 (33.7)
589 (44.8)
725 (55.2)
962 (73.2)
352 (26.8)
825 (62.8)
489 (37.2)
760 (57.8)
554 (42.2)
701 (53.3)
613 (46.7)
873 (66.4)
441 (33.6)
1222 (93.0)
92 (7.0)1274 (97.0)
40 (3.0)852 (64.8)
462 (35.2)
206 (15.7)
1108 (84.3)
1233 (93.8)
81 (6.2)
1137 (86.5)
177 (13.5)

Elderly [587]363 (61.8)
224 (38.2)
330 (56.2)‡‡‡257 (43.8)
430 (73.3)
157 (26.7)
377 (64.2)
210 (35.8)
336 (57.2)
251 (42.8)
295 (50.3)
292 (49.7)
345 (58.8)‡‡242 (41.2)
558 (95.1)‡‡
29 (4.9)562 (95.7)
25 (4.3)
377 (64.2)
210 (35.8)
156 (26.6)‡‡‡431 (73.4)
539 (91.8)
48 (8.2)
520 (88.6)
67 (11.4)[ ], number of patients; ( ), %.
§ Differentiated, papillary or tubular adenocarcinoma; undifferentiated, poorly differentiated or undifferentiated adenocarcinoma, or signet ring cell carcinoma.
|| D0, no dissection; D1, dissection of group-1 lymph nodes; D2, dissection of group-1 and -2 lymph nodes; D3, dissection of group-1 to -3 lymph nodes.
* P < 0.05: young versus middle-aged.
† P < 0.05: young versus elderly.
‡‡ P < 0.005: middle-aged versus elderly.
†† P < 0.005: young versus elderly.
*** P < 0.0001: young versus middle-aged.
††† P < 0.0001: young versus elderly.
‡‡‡ P < 0.0001: middle-aged versus elderly.

(Japanese Gastric Carcinoma Association, 1998). Patients were periodically checked for early recurrenceby diagnostic imaging (chest X-ray, double-contrast
barium meal study, upper gastrointestinal fiberscopy,
ultrasonography and computed tomography). All patients were monitored for at least 5 years. The causesof death and pattern of recurrence were determinedby reviewing the medical records, including laboratory data, ultrasonography, computed tomography,

scintigraphy, peritoneal puncture and laparotomy, orby direct inquiries addressed to bereaved families.
In some cases, postmortems were performed to establish the cause of death.
Statistical analysis
Association among factors was evaluated by thechi-squared test, and the significance of differences
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Gastric cancer in young patientsamong the means was determined by the MannWhitney U test. Survival curves were calculated according to the Kaplan-Meier method. Survival data
shown in the present study were cancer specific. To
this end, patients who died from another malignancy, another disease or an accident were treated as
censored cases in the survival analysis. Differences
between survival curves were examined with thelog rank test. Multivariate analysis was performedusing the Cox proportional hazards model and astepwise procedure. The covariates included gender,
age, histological classification, tumor size, depth ofinvasion, lymph node metastasis, lymphatic vesselinvasion, blood vessel invasion, peritoneal metastasis, liver metastasis and lymph node dissection. The
accepted level of significance was P < 0.05. Stat
View software (Abacus Concepts, Berkeley, CA)
was used for all statistical analyses.

Fig. 1. Survival curves in age-classified patients withgastric cancer. Five-year survival rates are 61.0%, 73.6%
and 68.1% in young, middle-aged and elderly patients,respectively. The prognosis in the middle-aged patients issignificantly better than that in either the young or elderly
patients (P < 0.05). [ ], number of patients; ( ), %.

Results

tasis was observed more frequently in the young
than in either the middle-aged (P < 0.005) or elderly
patients (P < 0.005).

Clinicopathologic characteristics of young
patients

Age and survival

Patient age ranged from 20 to 93 years with a meanof 62 years, and 1266 patients were male and 719,female. According to previous reports (Maeta etal., 1995; Saito et al., 2006), patients were divided
into 3 groups as follows: young patients aged under40 years; middle-aged patients aged 40 years andover and under 70 years; and elderly patients aged
70 years and over. The correlation between age andclinicopathologic factors is shown in Table 1. The
male-to-female ratio was significantly lower in theyoung patients than in either the middle-aged (P <0.0001) or elderly patients (P < 0.0001). Undifferentiated carcinoma was observed more frequently
in the young patients than in either the middle-aged(P < 0.0001) or elderly patients (P < 0.0001). Tumor
size in the young patients was significantly larger
than that in the middle-aged patients (P < 0.05). The
frequency of blood vessel invasion was significantly
lower in the young patients than that in the elderly
patients (P < 0.05). Furthermore, peritoneal metas-Among 1985 patients, 1731 underwent curative surgery and were included in the survival analysis. At
the time of analysis, the median follow-up of 1069
surviving patients was 108 months. Of 662 deaths,
334 were related to recurrence of gastric cancer,
328 were due to either an unrelated malignancy,
an unrelated disease or an accident. Five-year survival rates were 61.0, 73.6 and 68.1% in the young,middle-aged and elderly patients, respectively. The
prognosis of the middle-aged patients was significantly better than that of either the young or theelderly patients (P < 0.05; Fig. 1). We employed
Cox’s proportional hazards model and a stepwise
procedure to assess whether age represents an independent prognostic factor. The results showedthat age, tumor size, depth of invasion, lymph nodemetastasis, peritoneal metastasis, liver metastasis,
lymphatic or blood vessel invasion and curability
were independent prognostic factors (Table 2).
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H. Saito et al.

Table 2. Multivariate analysis of various clinicopathologic factors in patients with gastric carcinoma
Variable
Tumor size [continuous variable]
Age
Young (versus middle-aged)
Elderly (versus middle-aged)
Depth of invasion (T1–T4)*
Lymph node metastasis (N0–N3)†
Lymphatic vessel invasion (Ly0–Ly3)‡
Blood vessel invasion (V0–V3)§
Peritoneal metastasis (presence or absence)
Liver metastasis (presence or absence)
Curability

Hazardratio

95% confidence
interval

P
value

1.042

1.022–1.062< 0.0001

1.577
1.482
2.066
1.550
1.207
1.095
1.388
1.449
2.532

1.079–2.304
1.227–1.790
1.812–2.356
1.425–1.687
1.108–1.314
1.012–1.184
1.237–1.557
1.270–1.652
1.972–3.257

0.019< 0.0001< 0.0001< 0.0001< 0.00010.024< 0.0001< 0.0001< 0.0001* T1, tumor invasion of the lamina propria or submucosa; T2, invasion of the muscularis propria or the subserosa; T3,penetration of the serosa; T4, invasion of adjacent organs.
† N0, no regional lymph node metastasis; N1–N3, metastasis in group-1 to -3 lymph nodes.
‡ Ly0–Ly3, grade of lymphatic invasion.
§ V0–V3, grade of blood vessel invasion.

Age and recurrence patternFigure 2 shows the correlation between age andmode of recurrence. Peritoneal recurrence was morefrequently observed in the young patients than ineither the middle-aged or elderly patients (P < 0.05).
Moreover, hematogenous recurrence was more frequently observed in both the young (P < 0.01) andelderly patients (P < 0.001) than in the middle-aged
patients.

Discussion
Fig. 2. The correlation between age and mode of recurrence. Peritoneal recurrence is more frequently observedin young patients than either middle-aged or elderly patients (P < 0.05). Moreover, hematogenous recurrence ismore frequently observed in both young (P < 0.01) andelderly patients (P < 0.001) than middle-aged patients.

We have previously demonstrated that gastric cancer in the elderly is characterized by high frequency
of differentiated cancer, blood vessel invasion, hematogenous recurrence and poor prognosis (Saitoet al., 2006). Therefore, age might have an impact
on clinicopathologic characteristics, mode of recurrence and prognosis in patients with gastric cancer.
In the present study, the prognosis of gastric cancer patients in either the young age or oldage group was significantly worse than that in themiddle-aged population. On the other hand, there
are conflicting results with regard to the prognosis
of gastric cancer in young patients (Tso et al., 1987;
Okamoto et al., 1988; Kim et al., 2003). We havepreviously reported that prognosis of gastric cancer in elderly patients is poor (Saito et al., 2006).
Most previous studies have classified patients into 2groups, either young or the rest, and have compared
prognosis between the 2 groups. Therefore, the addition of elderly patients, whose prognosis was poor,
to the middle-aged patients, whose prognosis wasgood, might lead to different results for prognosis.
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Gastric cancer in young patientspatients, intensive chemotherapy should be considered even after curative operation.

In fact, in the present study, there were no significant differences in the prognosis between patients
aged ≤ 40 and those > 40 years (data not shown).
Therefore, we recommend classifying patients into
3 groups, the young, middle-aged and elderly like
we did in the present study, when the correlation between age and prognosis is determined.
As reported in previous papers (Bloss et al.,
1980; Mori et al., 1985; Sandler and Holland, 1987;
Tso et al., 1987), our results also demonstrated thatthe male-to-female ratio showed a predominance offemale patients in the young age group. Undifferentiated carcinoma was also observed more frequently
in the young age group. Moreover, the frequency
of peritoneal metastasis was high in the young patients. With regard to mode of recurrence, peritoneal recurrence was observed more frequently in theyoung than in either the middle-aged or elderly patients (P < 0.05). It has been reported that undifferentiated gastric cancer preferentially metastasizes tothe peritoneum (Moriguchi et al., 1991). Therefore,a high frequency of peritoneal recurrence might becorrelated with a high frequency of undifferentiatedgastric cancer in the young patients.
The Adjuvant Chemotherapy Trial of TS-1
for Gastric Cancer phase III trial has demonstrated
that S-1 was effective as adjuvant chemotherapy forJapanese patients who had undergone curative D2
gastrectomy for gastric cancer and were diagnosed
with pathological stage-2 or -3 disease (Sakuramotoet al., 2007). Therefore, a curative D2 dissection
and adjuvant chemotherapy with S-1 are now thestandard therapy for these patients in Japan (Sanoand Aiko, 2011). On the other hand, majority of patients included in the present study did not take S-1
after operation as S-1 became commercially available since 1999. Therefore, S-1 may significantly
improve the prognosis of the young patients sincecontinuation of S-1 adjuvant chemotherapy is considered better than the elderly patients.
In conclusion, gastric cancer in young patientshas unique characteristics, namely, a female predominance, a high frequency of undifferentiatedcancer and peritoneal metastasis and recurrence. On
account of the extremely poor prognosis in young

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Received June 19, 2012; accepted July 19, 2012
Corresponding author: Hiroaki Saito, MD61

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