Esophageal Carcinoma in Young Patients Masaki Mori, MD, Shinji Ohno, MD, Shinichi Tsutsui, MD, Hiroshi Matsuura, MD, Hiroyuki Kuwano, MD, and Keizo Sugimachi, MD Department of Surgery 11, Faculty of Medicine, Kyushu University, Fukuoka, Japan
The clinicopathological features of esophageal carcinoma were examined from the viewpoint of age differences in a study of 364 consecutively treated patients. The three groups studied were: group I, aged less than 49 years; group 11, aged between 50 and 69 years; and group 111, aged more than 70 years. There were no significant differences among the three groups with regard to sex ratio, site and length of the lesion, gross types, histological grade, depth of tumor invasion, vessel permeation, lymph node metastasis, TNM classification, incidence of incomplete resection, or crude actuarial 5-year survival curves. The malignant potentiality of the esophageal
carcinoma in young patients did not differ from that in older patients in terms of deoxyribonucleic acid distribution pattern. The only difference clearly evident between young and older patients was the number of hospital deaths due to complications: That of the young patients was significantly lower than that of the older patients ( p < 0.05). Esophageal carcinoma in persons aged less than 50 years appeared to behave biologically like the same neoplasm in older people, whereas gastric and colorectal carcinomas behave differently in various age groups.
C
Macroscopic and microscopic evaluations were made according to rules established by the Japanese Society for Esophageal Diseases [9]. An analysis of the deoxyribonucleic acid (DNA) content in the malignant cells was made of 182 cases, using the two-wavelength method described elsewhere [lo]. For statistical analysis of the clinicopathological data, the x2 test and Student’s t test were used.
arcinoma of the esophagus occurs mainly in the sixth, seventh, and eighth decades of life and is rare in patients aged less than 50 years. There are reports of clinicopathologicaldifferences in gastric [1-31 and colorectal (4-61 carcinomas between the young and the elderly. Few data are available on clinicopathological findings of young patients with esophageal carcinoma, however. We report our observations of 364 patients who underwent operation to remove a malignant lesion of the esophagus, especially from the viewpoint of age differences.
Material and Methods From 1965 to 1988, 364 Japanese patients with esophageal carcinoma were treated surgically in our institution. The age distribution is shown in Figure 1. Three groups were studied: group I included 28 patients aged less than 49 years at first diagnosis; group I1 included 254 patients aged 50 to 69 years; and group I11 comprised 82 patients aged more than 70 years. All records for each patient were reviewed with regard to location of the carcinoma, length and radiographic type of carcinoma seen on the barium study, preoperative adjuvant therapy, TNM classification [7], incidence of radical and palliative operations, postoperative complications, cause of death and hospital mortality, and 5-year survival. All patients were followed for 5 years or to the end of the study period. Survival curves were calculated using the Kaplan-Meier procedure [8], and all data relating to the long-term results were analyzed using the generalized Wilcoxon test. Accepted for publication Sep 30, 1989 Address reprint requests to Dr Mori, Department of Surgery 11, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan.
0 1990 by The Society of Thoracic Surgeons
(Ann Thorac Surg 1990;49:284-6)
Results Male preponderance was evident in all three groups. There was no difference in preoperative therapy among the three groups. The midesophagus was the area most commonly affected, and the ulcerative type was common to each group. There were no differences regarding site of
u)
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W ._ c m n \c
0
I
39
40
45
50
55
60
65
70
75
44
49
54
59
64
69
74
79
I
I
I
I
I
I
I
I
5 80 I
Age (years) Fig I. Age distribution of patients with esophageal carcinoma. 0003-4975/90/$3.50
Table 2. Histological Featuresa
Table 1. Clinical Data“
Variable Sex (WF) Site of carcinoma Cervical esophagus Thoracic esophagus
Group I (70 yr, n = 82)
86/14
83/17
84/16
4
5
4
7 12 5 Upper 60 59 66 Mid Lower 29 24 25 Esophagogram 25 19 23 Protruded Superficial 11 6 7 Ulcerative 64 75 70 Length of tumor in 6.73 2 3.54 6.47 k 2.54 6.11 +. 2.56 esophagogram (cm), mean 2 SD a
285
MORIETAL ESOPHAGEAL CARCINOMA IN THE YOUNG
Ann Thorac Surg 1990;49:284-6
Data are given in percentages.
lesion, radiographic type, or tumor length, as seen on the esophagograms (Table 1). Table 2 compares histological features of the tumors. There were no significant differences among the three groups with regard to histological type, depth of tumor invasion, vessel invasion, lymph node metastasis, TNM classification, or DNA distribution pattern. Data on resectability, postoperative complications, and mortality and cause of death are summarized in Table 3. Resectability did not differ among the three groups, and the frequency of postoperative complications was much the same among the three groups. In group I, 19 of 28 patients had incomplete resections; ten were the result of direct invasion to the trachea, bronchus, or aorta, and the other nine were the result of residual metastatic lymph nodes that could not be excised. The number of younger
Variable Histological types Well-differentiatedSCC Moderately differentiated SCC Poorly differentiatedSCC Otherb Tumor invasion into adventitia No invasion Invasion positive Invasion into neighboring tissue Vessel invasion Lymphatic Yes No Vascular Yes No Lymph node metastasis Yes No TNM classification I IIA IIB 111
IV DNA distribution pattern I I1 111 IV a
Data are given in percentages.
Group I Group I1 Group 111 (70 yr) n=28 14 50 29 7 n = 28 32 29 39
n=248 23 48 25 4 n = 254 24 43 33
n = 81 28 40 25 7 n = 82 24 43 33
n
n
n
=
27
=
243
=
78
56 44
55 45
56 44
30 70
23 77 n = 254 55 45 n = 254 8 26 7 39 20 n = 125 1 22 42 35
27 73
n = 28 57 43 n = 28 14 25 4 32 25 n = 14 0
21 29 50
n = 82 55 45 n = 82 10 20 5 45 20 n = 43 0
16 47 37
Esophageal carcinomas other than
SCC including adenocarcinomas, adenosquarnous carcinomas, undiffer-
entiated carcinomas, and rnucoepidermoid carcinomas. SCC
‘e
=
squarnous cell carcinoma.
looh
“h,
patients (group I) who died in the hospital with complications excluding recurrence of esophageal carcinoma was significantly low as compared with the number of older patients (group 111) ( p < 0.05). The 5-year actuarial survival curves for the three groups of patients are shown in Figure 2. There was no significant difference among the three groups.
y o u p II (n = 254)
L
0
I 1
2
3
4
5
YEARS AFTER OPERATION Fig 2. Survival curves of patients with esophageal cancer (%). Oneyear, 3-year, and 5-year survival rates are: 56.1%, 19.0%, and 9.5%, respectively, in group I; 54%, 26.3%, and 21.6%‘ respectively, in group 11; and 50.7%, 24.4%, and 16.7%, respectively, in group 111.
Comment Although gastric [l-31 or colorectal carcinomas often occur in patients in the second and third decades of life [5, 6, 111, esophageal carcinoma is rare in these age groups. We classified young patients with esophageal carcinoma as those aged less than 49 years. Young patients with gastric or colorectal carcinomas have been reported to be aged less than 30 [3], 35 [l, 21, or 40 [5, 61 years.
286
Ann Thorac Surg
MORIETAL ESOPHAGEAL CARCINOMA IN THE YOUNG
1990;49:284-6
Table 3. Postoperative Dataa
Variable Resectability Complete resection Incomplete resection Complications No Yes Lung Anastomotic leakage Death within 30 days after operation Hospital death due to complicationsb Within 30 days >30 days Cause of death Pneumonia Anastomotic leakage
Group I (70 yr, n = 82)
32 68
46 54
45 55
54 46 21 11 0
54 46 22 12 5
43 57 34 15 11
4c
9'
20
0 4
5' 5
11 9
4 0
4 2
12 1
Data are shown in percentages. Hospital death due to esophageal carcinoma excluded. ' Significance: p < 0.05 versus group 111.
a
Gastric carcinoma in the young differs from that which occurs in older patients, especially with regard to pathological features: poorly differentiated or diffuse-type carcinomas predominate histologically, infiltrative type is rather frequent even on gross inspection, intestinal metaplasia is less frequent, and gastritis occurs less commonly than in older patients [l-31. The usual sex ratio is altered, with a preponderance [3] or equivalence [I, 21 of women among younger patients and a consistent preponderance of men among older patients. Most young patients are in a clinically advanced stage, and the prognosis is poor [1-31. Colorectal carcinoma in the young also has features different from those of older patients. The predominant histological type of colorectal tumor in young patients is mucinous or poorly differentiated adenocarcinoma, with a clinically more aggressive nature and a predisposition to early metastasis [5, 61. In addition, delayed diagnosis in young patients can lead to a relatively poor prognosis [5, 61. In the current study of younger patients with esophageal carcinoma treated in our clinics, the pathological features such as histological differentiation, vessel invasion, and lymph node involvement showed no definite characteristics as compared with findings in older pa-
tients. The cytophotometric DNA pattern of esophageal carcinoma clearly defined the malignant potential [lo]. We [12] used a multivariate approach to assess the prognosis of patients with esophageal carcinoma and concluded that the DNA pattern appears to be an independent prognostic indicator. The ratio of favorable (types I and 11) to unfavorable (types 111 and IV) DNA patterns in young patients did not differ significantlyfrom findings in older patients. The pathological and DNA cytophotometric analysis in the current study suggests that the malignant potential of esophageal carcinoma in young patients does not differ from that in older patients. The survival rate of young patients with esophageal carcinoma did not differ from that of older patients. The only difference was that the rate of hospital death due to complications in the young was significantly low compared with rates in older patients. In conclusion, esophageal carcinoma in persons aged less than 50 years appears to behave biologically like other neoplasms that occur in older people, whereas gastric and colorectal carcinomas behave differently in various age groups.
References 1. Matley PJ, Dent DM, Madden MV, Price SK. Gastric carcinoma in young adults. Ann Surg 1988;208:593-6. 2. Tso PL, Bringaze WL 111, Dauterive AH, Correa P, Cohn I. Gastric carcinoma in the young. Cancer 1987;59:1362-5. 3. Mori M, Sugimachi K, Ohiwa T, Okamura T, Tamura S, Inokuchi K. Early gastric carcinoma in Japanese patients under 30 years of age. Br J Surg 1985;72:289-91. 4. Irvin TT. Prognosis of colorectal cancer in the elderly. Br J Surg 1988;75:419-21. 5. Umpleby HC, Williamson RCN. Carcinoma of the large bowel in the first four decades. Br J Surg 1984;71:272-7. 6. Pitluk H, Poticha SM. Carcinoma of the colon and rectum in patients less than 40 years of age. Surg Gynecol Obstet 1983;157335-7. 7. Hernanek P, Sobin LH, eds. TNM classification of malignant tumors. 4th ed. Geneva: International Union Against Cancer, 1987:4G2. 8. Kaplan EL, Meier P. Non-parametric estimations from incomplete observation. J Am Stat Assoc 1958;53:457-81. 9. Japanese Society for Esophageal Diseases. Guidelines for the clinical and pathologic studies on carcinoma of the esophagus. Jpn J Surg 1976;6:69-78. 10. Sugimachi K, Ide H, Okamura T, Matsuura H, Endo M, Inokuchi K. Cytophotometric DNA analysis of mucosal and submucosal carcinoma of the esophagus. Cancer 1984; 53:2683-87. 11. Steinberg JB, Tuggle DW, Postier RG. Adenocarcinoma of the colon in adolescents. Am J Surg 1988;156:46G2. 12. Sugimachi K, Matsuoka H, Ohno S, Mori M, Kuwano H. Multivariate approach for assessing the prognosis of clinical oesophageal carcinoma. Br J Surg 1988;75:1115-8.
The clinicopathological features of esophageal carcinoma were examined from the viewpoint of age differences in a study of 364 consecutively treated patients. The three groups studied were: group I, aged less than 49 years; group 11, aged between 50 and 69 years; and group 111, aged more than 70 years. There were no significant differences among the three groups with regard to sex ratio, site and length of the lesion, gross types, histological grade, depth of tumor invasion, vessel permeation, lymph node metastasis, TNM classification, incidence of incomplete resection, or crude actuarial 5-year survival curves. The malignant potentiality of the esophageal
carcinoma in young patients did not differ from that in older patients in terms of deoxyribonucleic acid distribution pattern. The only difference clearly evident between young and older patients was the number of hospital deaths due to complications: That of the young patients was significantly lower than that of the older patients ( p < 0.05). Esophageal carcinoma in persons aged less than 50 years appeared to behave biologically like the same neoplasm in older people, whereas gastric and colorectal carcinomas behave differently in various age groups.
C
Macroscopic and microscopic evaluations were made according to rules established by the Japanese Society for Esophageal Diseases [9]. An analysis of the deoxyribonucleic acid (DNA) content in the malignant cells was made of 182 cases, using the two-wavelength method described elsewhere [lo]. For statistical analysis of the clinicopathological data, the x2 test and Student’s t test were used.
arcinoma of the esophagus occurs mainly in the sixth, seventh, and eighth decades of life and is rare in patients aged less than 50 years. There are reports of clinicopathologicaldifferences in gastric [1-31 and colorectal (4-61 carcinomas between the young and the elderly. Few data are available on clinicopathological findings of young patients with esophageal carcinoma, however. We report our observations of 364 patients who underwent operation to remove a malignant lesion of the esophagus, especially from the viewpoint of age differences.
Material and Methods From 1965 to 1988, 364 Japanese patients with esophageal carcinoma were treated surgically in our institution. The age distribution is shown in Figure 1. Three groups were studied: group I included 28 patients aged less than 49 years at first diagnosis; group I1 included 254 patients aged 50 to 69 years; and group I11 comprised 82 patients aged more than 70 years. All records for each patient were reviewed with regard to location of the carcinoma, length and radiographic type of carcinoma seen on the barium study, preoperative adjuvant therapy, TNM classification [7], incidence of radical and palliative operations, postoperative complications, cause of death and hospital mortality, and 5-year survival. All patients were followed for 5 years or to the end of the study period. Survival curves were calculated using the Kaplan-Meier procedure [8], and all data relating to the long-term results were analyzed using the generalized Wilcoxon test. Accepted for publication Sep 30, 1989 Address reprint requests to Dr Mori, Department of Surgery 11, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan.
0 1990 by The Society of Thoracic Surgeons
(Ann Thorac Surg 1990;49:284-6)
Results Male preponderance was evident in all three groups. There was no difference in preoperative therapy among the three groups. The midesophagus was the area most commonly affected, and the ulcerative type was common to each group. There were no differences regarding site of
u)
c C
W ._ c m n \c
0
I
39
40
45
50
55
60
65
70
75
44
49
54
59
64
69
74
79
I
I
I
I
I
I
I
I
5 80 I
Age (years) Fig I. Age distribution of patients with esophageal carcinoma. 0003-4975/90/$3.50
Table 2. Histological Featuresa
Table 1. Clinical Data“
Variable Sex (WF) Site of carcinoma Cervical esophagus Thoracic esophagus
Group I (70 yr, n = 82)
86/14
83/17
84/16
4
5
4
7 12 5 Upper 60 59 66 Mid Lower 29 24 25 Esophagogram 25 19 23 Protruded Superficial 11 6 7 Ulcerative 64 75 70 Length of tumor in 6.73 2 3.54 6.47 k 2.54 6.11 +. 2.56 esophagogram (cm), mean 2 SD a
285
MORIETAL ESOPHAGEAL CARCINOMA IN THE YOUNG
Ann Thorac Surg 1990;49:284-6
Data are given in percentages.
lesion, radiographic type, or tumor length, as seen on the esophagograms (Table 1). Table 2 compares histological features of the tumors. There were no significant differences among the three groups with regard to histological type, depth of tumor invasion, vessel invasion, lymph node metastasis, TNM classification, or DNA distribution pattern. Data on resectability, postoperative complications, and mortality and cause of death are summarized in Table 3. Resectability did not differ among the three groups, and the frequency of postoperative complications was much the same among the three groups. In group I, 19 of 28 patients had incomplete resections; ten were the result of direct invasion to the trachea, bronchus, or aorta, and the other nine were the result of residual metastatic lymph nodes that could not be excised. The number of younger
Variable Histological types Well-differentiatedSCC Moderately differentiated SCC Poorly differentiatedSCC Otherb Tumor invasion into adventitia No invasion Invasion positive Invasion into neighboring tissue Vessel invasion Lymphatic Yes No Vascular Yes No Lymph node metastasis Yes No TNM classification I IIA IIB 111
IV DNA distribution pattern I I1 111 IV a
Data are given in percentages.
Group I Group I1 Group 111 (70 yr) n=28 14 50 29 7 n = 28 32 29 39
n=248 23 48 25 4 n = 254 24 43 33
n = 81 28 40 25 7 n = 82 24 43 33
n
n
n
=
27
=
243
=
78
56 44
55 45
56 44
30 70
23 77 n = 254 55 45 n = 254 8 26 7 39 20 n = 125 1 22 42 35
27 73
n = 28 57 43 n = 28 14 25 4 32 25 n = 14 0
21 29 50
n = 82 55 45 n = 82 10 20 5 45 20 n = 43 0
16 47 37
Esophageal carcinomas other than
SCC including adenocarcinomas, adenosquarnous carcinomas, undiffer-
entiated carcinomas, and rnucoepidermoid carcinomas. SCC
‘e
=
squarnous cell carcinoma.
looh
“h,
patients (group I) who died in the hospital with complications excluding recurrence of esophageal carcinoma was significantly low as compared with the number of older patients (group 111) ( p < 0.05). The 5-year actuarial survival curves for the three groups of patients are shown in Figure 2. There was no significant difference among the three groups.
y o u p II (n = 254)
L
0
I 1
2
3
4
5
YEARS AFTER OPERATION Fig 2. Survival curves of patients with esophageal cancer (%). Oneyear, 3-year, and 5-year survival rates are: 56.1%, 19.0%, and 9.5%, respectively, in group I; 54%, 26.3%, and 21.6%‘ respectively, in group 11; and 50.7%, 24.4%, and 16.7%, respectively, in group 111.
Comment Although gastric [l-31 or colorectal carcinomas often occur in patients in the second and third decades of life [5, 6, 111, esophageal carcinoma is rare in these age groups. We classified young patients with esophageal carcinoma as those aged less than 49 years. Young patients with gastric or colorectal carcinomas have been reported to be aged less than 30 [3], 35 [l, 21, or 40 [5, 61 years.
286
Ann Thorac Surg
MORIETAL ESOPHAGEAL CARCINOMA IN THE YOUNG
1990;49:284-6
Table 3. Postoperative Dataa
Variable Resectability Complete resection Incomplete resection Complications No Yes Lung Anastomotic leakage Death within 30 days after operation Hospital death due to complicationsb Within 30 days >30 days Cause of death Pneumonia Anastomotic leakage
Group I (70 yr, n = 82)
32 68
46 54
45 55
54 46 21 11 0
54 46 22 12 5
43 57 34 15 11
4c
9'
20
0 4
5' 5
11 9
4 0
4 2
12 1
Data are shown in percentages. Hospital death due to esophageal carcinoma excluded. ' Significance: p < 0.05 versus group 111.
a
Gastric carcinoma in the young differs from that which occurs in older patients, especially with regard to pathological features: poorly differentiated or diffuse-type carcinomas predominate histologically, infiltrative type is rather frequent even on gross inspection, intestinal metaplasia is less frequent, and gastritis occurs less commonly than in older patients [l-31. The usual sex ratio is altered, with a preponderance [3] or equivalence [I, 21 of women among younger patients and a consistent preponderance of men among older patients. Most young patients are in a clinically advanced stage, and the prognosis is poor [1-31. Colorectal carcinoma in the young also has features different from those of older patients. The predominant histological type of colorectal tumor in young patients is mucinous or poorly differentiated adenocarcinoma, with a clinically more aggressive nature and a predisposition to early metastasis [5, 61. In addition, delayed diagnosis in young patients can lead to a relatively poor prognosis [5, 61. In the current study of younger patients with esophageal carcinoma treated in our clinics, the pathological features such as histological differentiation, vessel invasion, and lymph node involvement showed no definite characteristics as compared with findings in older pa-
tients. The cytophotometric DNA pattern of esophageal carcinoma clearly defined the malignant potential [lo]. We [12] used a multivariate approach to assess the prognosis of patients with esophageal carcinoma and concluded that the DNA pattern appears to be an independent prognostic indicator. The ratio of favorable (types I and 11) to unfavorable (types 111 and IV) DNA patterns in young patients did not differ significantlyfrom findings in older patients. The pathological and DNA cytophotometric analysis in the current study suggests that the malignant potential of esophageal carcinoma in young patients does not differ from that in older patients. The survival rate of young patients with esophageal carcinoma did not differ from that of older patients. The only difference was that the rate of hospital death due to complications in the young was significantly low compared with rates in older patients. In conclusion, esophageal carcinoma in persons aged less than 50 years appears to behave biologically like other neoplasms that occur in older people, whereas gastric and colorectal carcinomas behave differently in various age groups.
References 1. Matley PJ, Dent DM, Madden MV, Price SK. Gastric carcinoma in young adults. Ann Surg 1988;208:593-6. 2. Tso PL, Bringaze WL 111, Dauterive AH, Correa P, Cohn I. Gastric carcinoma in the young. Cancer 1987;59:1362-5. 3. Mori M, Sugimachi K, Ohiwa T, Okamura T, Tamura S, Inokuchi K. Early gastric carcinoma in Japanese patients under 30 years of age. Br J Surg 1985;72:289-91. 4. Irvin TT. Prognosis of colorectal cancer in the elderly. Br J Surg 1988;75:419-21. 5. Umpleby HC, Williamson RCN. Carcinoma of the large bowel in the first four decades. Br J Surg 1984;71:272-7. 6. Pitluk H, Poticha SM. Carcinoma of the colon and rectum in patients less than 40 years of age. Surg Gynecol Obstet 1983;157335-7. 7. Hernanek P, Sobin LH, eds. TNM classification of malignant tumors. 4th ed. Geneva: International Union Against Cancer, 1987:4G2. 8. Kaplan EL, Meier P. Non-parametric estimations from incomplete observation. J Am Stat Assoc 1958;53:457-81. 9. Japanese Society for Esophageal Diseases. Guidelines for the clinical and pathologic studies on carcinoma of the esophagus. Jpn J Surg 1976;6:69-78. 10. Sugimachi K, Ide H, Okamura T, Matsuura H, Endo M, Inokuchi K. Cytophotometric DNA analysis of mucosal and submucosal carcinoma of the esophagus. Cancer 1984; 53:2683-87. 11. Steinberg JB, Tuggle DW, Postier RG. Adenocarcinoma of the colon in adolescents. Am J Surg 1988;156:46G2. 12. Sugimachi K, Matsuoka H, Ohno S, Mori M, Kuwano H. Multivariate approach for assessing the prognosis of clinical oesophageal carcinoma. Br J Surg 1988;75:1115-8.
