The Korea n J o urna l of Inte rnal Me dic ine Vol. 16 , No . 4 , Decembe r, 200 1
INT RO DUCT IO N
Ade nocarcinoma of the esophagus is increas ing in a number of countries, whereas the incide nce of gastric carcinoma is decreasing1- 7 )
. Except for an association with Barrett's esophagus , little is known about the etiology of these ca ncers . Ba rrett's esophagus is a complication of gastroesophageal reflux disease (GERD) a nd is rega rded as an important risk factor of esophageal ade nocarcinoma in western countries8 )
. The incide nce of esophagea l squamous cell carcinoma has decreased or remains stable in the USA a nd Europea n countries, whereas the incide nce of ade noca rcinoma is rapidly increas ing1 , 2 , 9 )
. But, the prevalence of esophagea l ade nocarcinoma has
not been s urveyed or reported in Korea , as fa r as we know. Therefore, we reviewed the medica l records of 969 patients with histologica lly prove n esophageal cance r during the last three decades (1970- 1999) to assess indirectly the ratio of esophageal adenocarcinoma to SCCA.
MA T E R IA LS A ND MET HO DS
Patie nts with histologica lly proven esophageal ca nce r between 1970 and 1999 were retrospective ly studied. The pathologic diagnosis of esophageal cance r was obtained by the eva luation of the specimen from s urgica l resection or e ndoscopic biopsy. The data were ta ke n from the Yonse i Medica l Ce nter. The patie nts were divided into three consecutive 10- year groups (group 1, 1970- 1979; group 2, 1980- 1989; group 3, 1990- 1999). Patie nts with SCCA or adenoca rcinoma that seconda rily invaded the
A S in g le C e n t e r ' s 3 0 Ye a r s ' Ex p e r ie n c e
o f Es o p h a g e a l Ad e n o c a rc in o m a
J u Ik S o n , M . D . , Hy o J in P a r k , M . D . , Ke e S u p S o n g , M . D . , Ki J o o n g Kim , M . D . , C h a n g Yo u l Le e , M . D . , S a n g In Le e , M . D . a n d
In S u h P a r k , M . D .
De p a rt m e nt o f Int e rn a l M e d ic in e , Y o n s e i U n iv e rs ity Co lle g e o f M e d ic in e , S e o u l, Ko re a B a c kg ro u n d : A d e n o c a rc in o m a o f t h e e s o p h a g u s h a s b e e n re p o rt e d t o b e in c re a s in g in in c id e n c e in a n u m b e r o f re g io n s t h ro u g h o u t t h e w o r ld , w h ile t h e in c id e n c e o f s q u a m o u s c e ll c a rc in o m a ( S C CA ) o f t h e e s o p h a g u s is m o s t ly s t a b le o r d e c re a s in g . T o e v a lu a t e t h e in c re a s in g t e n d e n c y o f a d e n o c a rc in o m a o f t h e e s o p h a g u s . M e t h o d s : w e s t u d ie d re t ro s p e c t iv e ly t h e re c o rd s o f p a t ie n t s w it h h is t o lo g ic a lly p ro v e n e s o p h a g e a l c a n c e r b e t w e e n 1 9 7 0 a n d 1 9 9 9 a t t h e Y o n s e i M e d ic a l C e n t e r. R e s u lt s : T o t a l c a s e s o f e s o p h a g e a l c a n c e r w e re 9 6 9 p a t ie n t s o f w h ic h t h e c a s e s o f a d e n o c a rc in o m a a n d S C CA w e re 2 7 p a t ie n t s a n d 9 1 8 p a t ie n t s , re s p e c t iv e ly . T h e ra t io o f e s o p h a g e a l a d e n o c a rc in o m a t o S C CA w a s 0 . 0 3 7 5 in t h e 1 9 7 0 s , 0 . 0 2 4 1 in t h e 1 9 8 0 s a n d 0 . 0 2 9 2 in t h e 19 9 0 s . T h e re w a s n o s t a t is t ic a l d if f e re n c e ( p = 0 .8 1 1) in t h e ra t io s o f a d e n o c a rc in o m a o f t h e e s o p h a g u s b e t w e e n t h e t h re e c o n s e c u t iv e 1 0 -y e a r g ro u p s . Co nc lu s io n : In c o n c lu s io n , u n lik e t h e U S a n d o t h e r w e s t e rn c o u nt rie s , it s e e m s t h at t h e ra t io o f e s o p h a g e a l a d e n o c a rc in o m a c o m p a re d t o S C CA h a s n o t in c re a s e d a m o n g p a t ie n t s w it h e s o p h a g e a l c a rc in o m a a t t h e Y o n s e i M e d ic a l C e n t e r.
Ke y Wo rds : esophageal adenocarcinoma, squamous cell carcinoma
Address reprint requests to： Hy o Jin Park, M.D., Departm ent of Internal Medicine, Yong Dong S everance Hospital, Yonsei University College of Medicine, Yong Dong P. O. Box 12 17, S eoul, Korea
A Single Center's 30 Years ' Exp erience of Es op hageal Adenocarcinom a
esophagus from a nonesophageal primary tumor a nd patients in whom the esophagus was involved with metastatic disease we re excluded. Esophagea l ca ncers we re divided according to the Internationa l Classification of Diseases of Oncology (ICD- O) morphologic crite ria into ade noca rcinoma a nd non- ade noca rcinoma . Three ce ll types we re defined as follows : adenoca rcinoma group, SCCA group a nd othe r ce ll types , including ne uroe ndocrine ca rcinoma , s ma ll ce ll ca rcinoma a nd adenosquamous cell carcinoma. Patients' age at diagnos is, tumor stage, tumor location, histologica l type and body mass index (BMI) we re recorded and ana lyzed.
Statistical analysis
The Statistical Analysis Syste m (SAS Inc., Ca ry, NC, USA) was used for all analysis. Tre nds from the three groups were compa red using chi- squa re test. The influence of BMI on two cell types was eva luated with t- test. The p va lue less than 0.05 was considered statistically s ignificant.
R E S ULT S
Between 1970 a nd 1999, a total of 969 cases of SCCA, ade nocarcinoma, or other ce ll type cance rs in the esophagus we re retrieved in the pathology records at the Yonse i Medica l Ce nte r. The re we re 918 patie nts with SCCA a nd 27 patients with esophageal ade nocarcinoma. Ove ra ll, SCCA was the most common ce ll type . Othe r ce ll types of esophagea l ca ncer cons isted of ade no-squamous ca rcinoma (n=4), s ma ll cell carcinoma (n=2), neuroendocrine carcinoma (n=1) and undifferentiated type (n=17). The distribution of the ce ll types of esophagea l ca rcinomas is shown in Table 1.
Ta b le 1. The d is tribut io n o f the c e ll type s o f e s o pha g e a l c a rc ino ma s
Cell type of esophageal cancer
Patient numbers Percent
Sex (M:F) Squamous cell carcinoma
Adenocarcinoma Undifferentiated
Adenosquamous cell carcinoma Small cell carcinoma
Neuroendocrine carcinoma 918 27 17 4 2 1 94.7% 2.8% 1.8% 0.4% 0.2% 0.1% 862:56 25:2 17:0 4:0 2:0 1:0
The mean age of patie nts with esophageal cancer was 6 1.1±8.8 years (mea n age of adenoca rcinoma group a nd SCCA group, 62.2±10.6 a nd 61.1±8.7 years , respectively) and the mean height a nd body weight we re 166.0±6.7 cm a nd 53.0± 15.9 kg, respective ly.
We discovered 541 cases (56.6%) of esophageal ca ncer in the mid- esophagus, 207 cases (21.7%) in the upper esophagus and 207 cases (21.7%) in the lower esophagus (Table 2). A tota l of 27 cases of esophageal ade noca rcinoma were identified in this study. The les ion s ite of 21 cases was located in the lower esophagus and that of the remaining 6 cases was located in the mid- esophagus . The ratios of adenoca rcinoma to SCCA we re 10.4% (2 1/201) in the lower esophagus, 1.1% (6/529) in the mid- esophagus and 0.0% (0/20 1) in the upper esophagus . Thus, ade noca rcinoma was located in the lowe r esophagus more frequently tha n in the mid or upper esophagus with a statistica l significa nce (p =0.00 1).
Ta ble 2 . The lo c atio n of e s o pha ge a l c a nc e rs
Tumor location in
the esophagus Tota l SCCA* Ade no
† Othe r ce ll type Uppe r 207 (2 1.7%) 20 1 0 6 Mid 54 1 (56.6%) 523 6 12 Lowe r 207 (2 1.7%) 180 2 1 6 Tota l 955(100.0%) 9 14 27 24 (miss ing data=14)
SCCA*, s qua mous ce ll ca rcinoma ; Adeno†, ade noca rcinoma The ratios of the ade nocarcinoma group to the SCCA group among the three groups we re 0.0375, 0.0241 and 0.0292 for group 1, 2 and 3, respectively (p =0.8 11). The ratios of the adenoca rcinoma group to the SCCA group have not risen in the three groups (Table 3).
Ta ble 3 . The dis tributio n of the e s o phag e a l c a nc e rs ac c o rd ing to the c e ll type s in e a c h g ro up
Adenoca rcinoma SCCA* Group 1 (1970- 1979) 3 (3.75%) 77 (96.25%) Group 2 (1980- 1999) 6 (2.4 1%) 243 (97.59%) Group 3 (1990- 1999) 18 (2.92%) 598 (97.08%)
Tota l 27 918
(p =0.811)
SCCA*, squamous ce ll ca rcinoma
In the adenocarcinoma group, the mean BMI was 19.6±6.3 and that of the SCCA group was 19.4±5.6 (p=0.3445).
J.I. S on, H.J. Park, K.S . S ong, K.J. Kim, C. Y. Lee, S.I. Lee, I.S . Park
D IS C US S IO N
Our study of esophagea l ade noca rcinoma has seve ral limitations in methodology. At first, it is a s ingle ce nte r's experience of 30 yea rs about esophageal ca ncer and so the res ults of this study cannot represe nt the ove rall preva lence of esophagea l adenoca rcinomas in Korea . At le a st s eve ra l multi- ce nte r studie s a re ne eded for the purpose of defining the preva le nce of esophageal ade noca rcinoma in Korea. But our study tried to find indirect evidence of an increasing tendency of esophageal ade noca rcinoma a nd the result see ms to be that the ratio of adenoca rcinoma to SCCA has not increased in patients with esophagea l carcinoma in a the past three decades in single medica l ce nte r in Korea.
From the late 1970s, a significa nt increase in the incide nce of ade nocarcinoma of the esophagus a nd gastric ca rdia has been reported from many countries , including the US1 - 3 ), the United Kingdom4 ), France5 ) a nd Sweden6 )
. In the US, adenocarcinoma of the esophagus has continued to increase in freque ncy in the ea rly 1990s a nd a n estimated 25,000 people die eve ry year of this ca ncer7 )
. Lord et al. reported from a la rge scale preva lence study done in 19981 0 ) that the incidence of esophagea l ade nocarcinoma in me n has increased evide ntly in Austra lia . The incide nce of SCCA of the esophagus is mostly stable or decreasing whilst that of ade noca rcinoma of the esophagus has bee n reported to be increas ing in incidence in a numbe r of regions1 , 2 , 9 )
. These two types of esophageal cance r have distinctly differe nt de mographic patterns (i.e., the incide nce of squamous ce ll tumors is more tha n 5 times highe r a mong black men tha n among white me n, whe reas the incide nce for adenoca rcinoma is more tha n three times higher in white me n compa red with black men).
Although adenocarcinoma of the esophagus has been increas ing rapidly in ma ny regions of the world, the ris k factors of the cance r are largely unknown. The proposed ca ndidates as risk factors for adenoca rcinoma of the esophagus a re Barrett's esophagus, high BMI, alcohol and tobacco use, H2 receptor antagonist use, Helicobacter pylori (H. pylori) infection, etc.
Ade nocarcinomas of the esophagus ca n poss ibly a rise from mucosa l glands , submucosa l glands , ectopic gastric mucos a a nd Ba rrett's e s ophagus . Ra re ca s es of esophagea l ade noca rcinomas in the uppe r esophagus ha ve been described in the lite rature1 1 ).
The rece ntly reported increas ing incidence of ade no-carcinomas in the lower esophagus is related to ma ligna nt
tra nsformation of Barrett's esophagus . In Barrett's esoph-agus , the normal squamous epithelial lining of the lower esophagus , damaged by gastroesophageal reflux, is replaced by columna r epithe lium. Ba rrett's esophagus is a precursor lesion for ade noca rcinoma of the esophagus and gastric cardia and is more common in men12 )
. Patie nts with Barrett's esophagus have a 30～125 times increased ris k of developing esophageal carcinoma1 3 - 15 ). Barrett's esophagus is thought to a rise in conditions with prolonged reflux of duodenal contents into the esophagus16 - 18 )
. It is be lieved that GERD is more common in obese patients , especially those with abdominal obesity. Brown et al. reported that obesity (upper quartile of BMI) was associated with a three times higher risk of adenocarcinoma than the lowest quartile19 )
. The mechanism by which obesity might affect the risk of esophagea l ade nocarcinoma is unclea r, a lthough it may be linked to the predispos ition of obese individuals to GERD a nd to the commonly associated hiata l hernia2 0 ). Reflux esophagitis is a major risk factor for Barrett's esophagus2 1), which in turn is a precursor les ion for esophageal adenocarcinoma . As for BMI, our observation s howed no stastistically s ignificant differe nce between adenocarcinoma and SCCA groups (BMI of the adenocarcinoma group=19.6, BMI of the SCCA group=19.4, p =0.8331).
There is no report on the preva le nce a nd incide nce of reflux esophagitis in the genera l Korea n population. In Korea , it is ge ne rally accepted that the prevale nce and incide nce of reflux esophagitis are lowe r tha n those in the weste rn countries . Yi et al. found that the estimated age- adjusted preva lence of endoscopica lly- proven reflux esophagitis in a ge ne ral health screening population was 2.7%, which was ve ry low preva lence compared to those from weste rn countries2 2 )
. The study of Yeom et al. a lso s howed that the preva lence of reflux esophagitis in patients with symptoms of gastrointestina l tract was 5.4%, which mea ns that the prevalence of reflux esophagitis in the Korea n population would be much lower tha n that of western countries2 3 )
. But it is expected that GERD in Korea may increase in incide nce because of the increase in the obese population due to westernized diet and life style.
In conclus ion, unlike the western countries including US, our retrospective study found that the ratio of ade noca rcinoma to SCCA has not increased in patients with e sopha gea l ca rcinoma in the pa st three de ca de s at a s ingle medica l ce nter in Korea. However, furthe r e pide miologic studies a re ne e de d to eva luate the possibility of an increasing tendency to develop esophageal ade noca rcinoma in Korea in the near future .
A Single Center's 30 Years ' Exp erience of Es op hageal Adenocarcinom a
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