Gastric Carcinoma in Young Adults. Hitoshi Katai, Mitsuru Sasako, Takeshi Sano and Keiichi Maruyama

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1 Gastric Carcinoma in Adults Hitoshi Katai, Mitsuru Sasako, Takeshi Sano and Keiichi Maruyama Department of Surgical Oncology, National Cancer Center Hospital, Tokyo ' Among 4608 patients with gastric carcinoma treated during a 20-year period from 1971 to 1990, 328 (7.1%) were less than 40 years of age. The clinicopathologic features and treatment results in this young group were compared with those for older gastric carcinoma patients (40-79 years of age, control group). In the young group, the male/female ratio and the prevalence of tumors in the lower third of the stomach were both lower than in the control group, and undifferentiated-type adenocarcinomas with diffusely infiltrative growth predominated. The TNM stage distribution and the proportion of curative resections were similar in the two groups. The overall cumulative 5-year survival rates were also similar, although that of patients who underwent curative resection was higher in the young group, due probably to the low rate of death from other causes. There was no difference in the recurrence rates after curative resection between the two groups. Contrary to widely held belief, the prognosis of young patients with gastric carcinoma is not poorer than that of older patietns if the disease is diagnosed at a reasonably early stage. (Jpn J Clin Oncol 26: , 1996) Key words: Gastric carcinoma patient Surgical treatment Prognosis Introduction As gastric carcinoma develops only rarely in young adults, it has often reached an advanced stage by the time of diagnosis and is therefore fatal. 1 " 7 ' The disease has long been thought to be biologically more malignant in the young than in older patients. However, this assumption has never been tested, due probably to insufficiency of patient numbers for a stage-by-stage survival comparison. Is gastric carcinoma in young adults really more aggressive and associated with a poorer prognosis than in older patietns? To address this issue, we investigated a large series of gastric cancer patients treated in a single institution with special reference to young adults. Patients and Methods Between 1971 and 1990, 4608 patients underwent laparotomy for gastric carcinoma at the Department Received: August 28, 1995 Accepted: November 17, 1995 For reprints and all correspondence: Hitoshi Katai, Department of Surgical Oncology, National Cancer Center Hospital, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104 of Surgery, National Cancer Center Hospital, Tokyo, and of these, 328 (7.1%) weritiess than 40 years of age (young group). The age and sex distribution of the patients in this group is shown in Table I. The mean age was 34.4 yr. The control group comprised patients aged 40 to 79 years, who accounted for 90% of the entire study population (mean age: 59.9 yr). The surgical specimens were examined and recorded according to the rules of the Japanese Research Society for Gastric Cancer 8 ' and the ptnm pathological classification. 9 ' The tumors were reclassified histologically as differentiated or undifferentiated adenocarcinoma, placing papillary and tubular adenocarcinomas in the former group, and poorly differentiated adenocarcinoma, signet ring cell carcinoma and mucinous adenocarcinoma in the latter. Vital statistics for all patients were obtained from the city registry office and follow-up records. Cumulative 5-year survival rates including operative deaths were calculated by the life-table method with Greenwood's 5% standard error. 10 ' The chi-squared test was-employed to assess statistical significance. 139

2 KATAI ET AL. Table I. Age and Sex Distribution of the Group Age range Total No. of patients Male Female Results All % Clinicopathologic Features Clinicopathologic features of the tumors are compared and listed in Table II. The male: female ratio was 1.4:1 in the young group and 2.1:1 in the control group. In the young group, the bulk of the tumor was located more frequently in the middle third of the stomach than in the lower third, whereas in the control group these two portions of the stomach were equally affected. The prevalences of tumors in the upper third of the stomach were similar in the two groups. With regard to macroscopic tumor type, approximately 40% of patients in both groups had superficial-type tumors. Advanced carcinomas, on the other hand, showed a contrast in gross type distribution: the proportion of tumors with infiltrative growth (Borrmann types 3 and 4) was significantly higher in the young group than in the control group. Type 4 (linitis plastica) tumors accounted for a quarter of all advanced tumors in the young adults. There was a clear contrast between the two groups in the histology of the tumors. When the tumors were histologically reclassified into differentiated or undifferentiated carcinomas, the latter predominated (81%) in the young group, while the two types were equally common in the control group. The distribution of tumor invasion depth was essentially the same in the two groups, and the rates of lymph node metastasis were also quite similar. Consequently, there was no significant difference in the distribution of TNM stages between the two groups. Surgical radicality was then compared (Table III). The proportions of curative and palliative resections, as well as exploratory laparotomies, were similar in the two groups. Survival Five-year survival rates (5-YSR) were compared between the two groups under various conditions, Table II. Clinicopathologic Features of Gastric Carcinomas in the (<40 years old) and (40-79 years old) Groups Sex Male/female Tumor location Upper third Middle third Lower third Macroscopic type Superficial Borrmann 1 Borrmann 2 Borrmann 3 Borrmann 4 Unclassified Histologic type Differentiated papillary well differentiated moderately differentiated Undifferentiated poorly differentiated signet-ring cell mucinous Depth of tumor invasion* Mucosa Submucosa Muscularis propria Subserosa Serosa or neighboring organs 328 (100%) 192: (18.0) 169 (51.5) 100 (30.5) 124 (37.8) 3 (0.9) 26 (7.9) 118(36.0) 52 (15.9) 5 (1.5) 63 (19.2) 7 (2.1) 17 (5.2) 39(11.9) 265 (80.8) 114(34.8) 143 (43.6) 8 (2.4) 81 (26.4) 43 (14.0) 29 (9.4) 45 (14.7) 109 (35.5) Lymph node involvement (TNM) Negative 159 (48.5) Nl 36(11.0) N2 85 (25.9) >N2 45 (13.7) 3 (0.9) Stages (TNM) I 146 (44.5) II 30(9.1) III 68 (20.7) IV 64 (19.5) 20 (6.2) 4280 (100%) 2876 : (20.4) 1765 (41.2) 1644 (38.4) 1759 (41.1) 93 (2.2) 675 (15.8) 1290 (30.1) 412 (9.6) 51 (1.2) 2177 (50.9) 319 (7.5) 960 (22.4) 898 (21.0) 2103 (49.1) 1174 (27.4) 788 (18.4) 141 (3.3) 939 (23.3) 804 (19.9) 400 (9.9) 519 (12.9) 1369 (34.0) 2182 (51.0) 666 (15.6) 865 (20.2) 525 (12.2) 42 (1.0) 2009 (46.9) 448 (10.5) 798 (18.6) 819 (19.1) 206 (4.9) *, resected case only;, no statistically significant difference. Table III. Surgical Radicality Curative resection Palliative resection Exploratory laparotomy/others 328 (100%) 259 (79.0) 48 (14.6) 21 (6.4) 4280 (100%) 3477(81.2) 554 (12.9). 249 (5.9) 140 Jpn J Clin Oncol 26(3) 1996

3 GASTRIC CARCINOMA IN YOUNG ADULTS Table IV. Cumulative 5-year Survival Rates of the Two Groups Overall Curative resection All Stage Stage I Stage II Stage III Stage IV Histologic type Differentiated Undifferentiated Palliative resection 63.1% 64.8"% 80.0% 82.8% 98.6% 100% 86.6% 92.0% 52.8% 54.9% 12.5% 14.3% 92.7% 92.3% 76.5% 80.2% 0% (n) (328) (310) (259) (243) (146) (143) (30) (25) (67) (61) (16) (14) (55) (52) (204) (191) (48) 60.1% 64.9% 72.8% 80.2% 90.9% 98.6% 73.4% 83.3% 45.8% 51.8% 15.9% 15.7% 76.6% 85.7% 68.4% 74.0% 4.5% (n) (4280) (3693) (3477) (2943) (2002) (1737) (442) (359) (761) (610) (272) (237) (1882) (1561) (1596) (1382) (554) P n, number of patients;, no statistically significant differences. Table V. Causes of Death within 5 Years after Curative Resection Cause of death Recurrence Other diseases (Other cancers) Operative death Alive 259 (100%) 41 (15.8) 5 (1.9) (0 (0)) 1 (0.4) 4(1.5) 208 (80.4) P 3477 (100%) 558 (16.0) 241 (6.9) (76 (2.2)) 17 (0.5) 89 (2.6) 2572 (74.0) and the results are listed in Table IV. When surgery was curative, the 5-YSR for the young group was significantly higher than that of the control group. However, the control group had a significantly higher rate of death from other causes, including other cancers, than the young group (Table V). When the patients who had died of other causes were excluded, the difference in survival between the two groups disappeared. The 5-YSR after curative resection was investigated stage by stage. The survival rates in the two groups were similar except at stage I. However, this difference also disappeared when patients who had died of other causes were excluded. The 5-YSR after curative resection was compared between the groups by reference to histological tumor types. The 5-YSRs of the young group were significantly higher than those of the control group for both differentiated and undifferentiated tumors. The difference in survival also disappeared upon exclusion of patients who died of other causes. The 5-YSRs~ of the patients with differentiated tumors were better than those of patients with undifferentiated tumors in both groups (P). The 5-YSRs were then investigated by reference to tumor location. The 5-YSRs for young patients with tumors located in the upper, middle and distal thirds of the stomach were 45.5%, 67.1% and 60.3%, respectively, whereas those for control patients were 43.5%, 68.4% and 65.6%, respectively. No difference in survival was observed between the two groups. Discussion Studies of gastric carcinoma in the young have most frequently defined patients under 30 or 35 years of age as 'young', because intestinal metaplasia, an aging process affecting the gastric mucosa, is thought to begin at around this time of life. 1 " 71 "" 14 ' However, the actual numbers of patients younger than 35 years have been too small (<2% in our series) for determination of statistical significance. 1 "* 11 " 14 ' In this study, we extended the range up to 39 years of age, because preliminary analyses had revealed that inclusion of patients aged 36 to 39 years did not alter the characteristics of the younger patient population. Consequently 141

4 KATAI ET AL. our 'young group' included 328 patients (7% of the whole study population), and this number was sufficient for survival analyses. The study group did not include patients who never underwent surgery, an approach adopted only exceptionally in Japan. However, the young group did include 48 (14.6%) patients who underwent palliative resection and 21 (6.4%) who underwent exploratory laparotomy only. The clinicopathologic characteristics of the young group in our study were comparable with those of previous reports: a low male/female ratio, 1 " 4 ' 6 ' 7 ' 11 ' 14 * few tumors in the lower third of the stomach, 1 " and predominance of undifferentiated tumors with diffusely infiltrative growth " 14) The location and histological type of the tumor, but not the sex ratio, appear to be related to the prevalence of atrophic gastritis and intestinal metaplasia. 15 " 18 ' The stage distribution and survival rates observed in young patients in the present study were noteworthy. Many investigators have reported low resectability and extremely poor survival in young patients, apparently reflecting the advanced stage at which these carcinomas are generally diagnosed. 1 " 7 ' 11 " 14) In our series, however, the resectability (93.6%) and the proportion of curative resections (79%) in the young group were much higher than those reported previously, 4 ' 5>T 13> 14) > " and did not differ significantly from those of the control group. The TNM stage distributions in the two groups were also quite similar. It is widely believed that the dramatic increase in gastric cancers detected at an early stage in Japan in recent decades is attributable primarily to mass screening. 19) However, this is not the case for patients under 40 years of age because mass screening is not advocated for this generation. Rather, early detection in young adults is attributable to widespread utilization of endoscopy for evaluating vague symptoms such as epigastric discomfort or dyspepsia. Endoscopy has become a relatively common practice even for individuals below 40 years of age. The present results support the British approach to early detection of gastric cancer in the general population. 20 ' The overall survival curves for the young and control groups were almost identical. The 5-YSR for the young group, after curative resection, was also similar to that of the control group in terms of the results of stage by stage analysis, i.e. excluding patients who died of other causes. Gastric carcinoma in young individuals has long been believed to show more aggressive biological behavior and poorer prognosis than that in older patients, especially the undifferentiated type. Our study showed that although the 5-YSR of young patients with undifferentiated tumors was indeed poorer than that of patients with differentiated tumors, the outcome for these patients was rather better than for control patients with undifferentiated tumors. Moreover, there was no significant difference in survival between young patients with undifferentiated tumors and control patients with differentiated tumors. Our results suggest that, although gastric carcinoma in the young does show some specific features, it is not more malignant than that in older patients when the disease is diagnosed at a reasonably early stage. As in all patients with gastric carcinoma, the key to improved survival is early diagnosis. References 1) McNeer G: Cancer of the stomach in the young. Am J Roentgnol 45: , ) Bedikian AY, Khankhanian N, Heilbrun LK, Bodey GP, Stroehlein JR, Valdivieso M: Gastric carcinoma in young adults. South Med J 72: , ) Bloss RS, Miller TA, Copeland EM III: Carcinoma of the stomach in the young adult. Surg Gynecol Obstet 150: , ) Bellegie NJ, Dahlin DC: Malignant disease of the stomach in young adults. Ann Surg 138: 7-12, ) Block M, Griep AH, Pollard HM: The occurrence of gastric neoplasms in youth. Am J Med Sci 215: , ) Tamura PY, Curtiss C: Carcinoma of the stomach in the young adult. Cancer 13: , ) Tso PL, Bringaze WL III, Dauterive AH, Correa P, Cohn I Jr: Gastric carcinoma in the young. Cancer 59: , ) Japanese Research Society for Gastric Cancer: Japanese Classification of Gastric Carcinoma.' Kanehara, Tokyo ) TNM Classification of Malignant Tumors, 4th ed, Springer, Berlin ) TNM General Rules, 2nd ed, Union Internationale Contra le Cancrum, Geneve ) Matsusaka T, Soejima K, Kodama Y, Saito T, Inokuchi K: Carcinomas of the stomach in the young adults. Jpn J Surg 6: , ) Umeyama K, Sowa M, Kamino K, Kato Y, Satake K: Gastric carcinoma in young adults in Japan. Antkancer Res 2: , ) Matley PJ, Dent DM, Madden MV, Price SK: Gastric carcinoma in young adults. Ann Surg 208: , ) Okamoto T, Makino M, Kawasumi H, Kimura O, Nishidoi H, Kaibara N, Koga S: Comparative study of gastric cancer in young and aged patients. 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5 GASTRIC CARCINOMA IN YOUNG ADULTS histological appearances. Gann 59: , ) Hisamichi S, Fukao A, Tsubono Y: Evaluation of 17) Imai T, Kubo T, Watanabe H: Chronic gastritis in mass screening for stomach cancer. In Gastric Japanese with reference to high incidence of gastric Cancer, Nishi M, Ichikawa H, Nakajima T, carcinoma. / Natl Cancer Inst 47: , 1971 Maruyama K, Tahara E, eds, Springer-Verlag, 18) Nagayo T: Classification of gastric carcinoma. In Tokyo. pl6-25, 1993 Gastric Cancer, Nishi M, Ichikawa H, Nakajima T, 20) Hallisey MT, Allum WH, Jewkes AJ, Ellis DJ, Maruyama K, Tahara E, eds, Springer-Verlag, Fielding JW: Early detection of gastric cancer. BMJ Tokyo. p53-65, : ,