GastroenterologiaJaponica Copyrzght 9 1979 by TheJapanese Society of Gastroenterology

Vol. 14, No. 2 Printed inJapan

--Original Article-CLINICAL

STUDIES

ANTIGEN

IN

ON

CARCINOEMBRYONIC

PANCREATIC

CANCER

Takashi Y A M A U C H I , M.D., Akihiro F U N A K O S H I , M.D., Hideyuki W A K A S U G I , M.D., Akira H A Y A K A W A , M.D. a n d Hiroshi IBAYASHI, M.D..,

The Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, 812Japan

Summary We studied serum carcinoembryonic antigen (CEA) levels in 82 patients. Thirty-four of these had benign diseases while 48 had malignant diseases. Highest incidence and levels of CEA occurred in the sera of patients with pancreatic cancer and stomach cancer. In this paper we focused our particular attention on the serum CEA of 25 pancreatic cancer patients, and examined differences in serum CEA levels in relation to histologic differentiation and sites of pancreatic cancer. No statistical difference in serum CEA level was found among various histologic types and sites of the pancreatic cancer. Clinical courses of two patients with pancreatic cancer were also studied. Serial determinations of CEA levels are most useful in assessing the effect of operation or chemotherapies and are a useful indicator for differentiating pancreatic cancer from chronic pancreatitis but cannot be a conclusive factor for the diagnosis. Finally, we correlated serum CEA levels with those of RNase and confirmed a positive correlation.

Key Words: carcinoembryonic antigen, pancreatic cancer.

Introduction Currently there

is increasing interest in

serum factors that are related qualitatively or quantitatively to the presence of neoplasms in humans~,~). In 1965 Gold et al. described CEA a n d f o u n d it in all a d e n o c a r c i n o m a arising from the entodermally derived digestive tract epithelium3,4). Increased levels of CEA in patients with pancreatic cancer were noted by several investigators more t h a n a decade agoS,6). Nevertheless, only a few systematic Received September 29, 1978. Accepted November 13, 1978. Address request for reprints to: Takashi Yamauchi, M.D., 3rd Department of Internal Medicine, Faculty of Medicine, Kyushu University, 1-1 Maedashi 3-chome, Higashi-ku, Fukuoka City, 812Japan.

attempts to d e t e r m i n e the usefulness of the assay in clinical study have appeared. Perhaps because CEA elevations were not f o u n d in all studies of cancer patients a n d because high levels of the CEA were f o u n d in a variety of unrelated non-neoplastic diseases~,S), the source, n a t u r e a n d biological significance of CEA have not been clarified. In this p a p e r we have studied the diagnostic usefulness of CEA assay in pancreatic cancer a n d c o m p a r e d the CEA levels with histologic differentiation a n d sites of the t u m o r . W e have also tried to correlate the CEA levels with those of RNase which is produced in the pancreas a n d elevated only in pancreatic cancer9,a0). This, together with correlation of CEA levels with the clinical courses of pancreatic cancer

April 1979

patients, findings.

Clinical Studies on Carcinoembryonic Antigen in Pancreatic Cancer

has

yielded

several

interesting

123

Serum RNase was measured as described previouslyl0), using polycytidylic acid as suhstrate.

Materials and Methods Results

CEA determinations have been carried out in a total of eighty-two patients. Of these, thirty-four had benign diseases and forty-eight malignant. Among the benign diseases there were 14, 15 and 5 cases of chronic pancreatitis, liver cirrhosis and chronic hepatitis respectively. Among the malignant diseases there were 25, 6, 7, 7 and 3 cases of pancreatic cancer, hepatoma, gastric cancer, colon cancer and lung cancer respectively. Chronic pancreatitis was diagnosed by Pancreozymin-Secretin test or by the presence of pancreatolithiasis. Liver cirrhosis and chronic hepatitis were diagnosed by bioposy. The diagnosis of pancreatic cancer and other malignant diseases were proved by biopsy or autopsy. In addition, we observed two clinical courses of pancreatic cancer. Serum CEA was measured by CEA-RIA kit (Dinabot Co., Ltd.)11).

Positive rate

60%

7%

0%

1)

Serum CEA levels in various diseases Serum CEA values ranged from 0.1 to 44 ng/ml in all patients (Fig. 1). Levels above 2.6 ng/ml were reached by 68% of the patients with pancreatic cancer (17 of 25 patients), 7% of those with chronic pancreatitis, 0% of those with hepatoma, 9.7% of those with liver cirrhosis, 0% of those with chronic hepatitis, 71% of those with gastric cancer, 33% of those with colon cancer, and 33% of those With lung cancer. 9.) Serum CEA of pancreatic cancer: its relation to histologic differentiation and hepatic metastasis (Fig. 2). Serum CEA levels ranged from 0.6 ng/ml to 36 ng/ml (mean _ SD 10.2+9.99) for pancreatic cancer. Out of patients with pancreatic cancer, 16 patients with ductal cell adenocarcinoma had CEA levels ranging from 1.1 ng/ml to 36 ng/ml; 2 with anaplastic cell

27%

0%

71%

33%

3~

CEA nglml

5.0 2.5 0

oi9149 i "i

9149

......

i

~149176I;o%%%;

Pancreas Chronic Hepatoma Ca Pancreatitis

Liver Cirrhosis

gee 9o

9

9

Chronic StomachCa Hepatitis

Fig. 1. serumCEA levelsin variousdiseases.

e 9 1 4o9 Colon

Ca

olo Lung Ca

124

Vol. 14, No. 2

T. Y A M A U C H I E T AL.

Ductar cell Men0carcinoma

0000

I9

9

9

9

oo

oo

9

9

( 9+9.71

o

A naplastic cell

carcinoma Acinar cell carci noma

o

o

Islet cell

carc.inoma 2.5

I0

20

30

ng/ml

T

upper limit

Fig. 2.

Serum CEA of pancreatic cancer: Relation to tumor histology and hepatic metastasis. 9 hepatic metastasis C) no hepatic metastasis (mean ---standard deviation)

I Head

,o o 9

Body &Tail

10~ oo

9e

t.'o~176 9 9

@

9

9 9

oe

2.5

Tupper

I0

20

( 9+11.6 )

9 30

( 10.8+_.9,6I

ng/ml

limit

Fig. 3. Serum CEA of pancreatic cancer: Relation to sites. 9 hepatic metastasis C) no hepatic metastasis (mean -+standard deviation)

c a r c i n o m a , from 1.2 n g / m l to 10 n g / m l ; 2 with acinar cell c a r c i n o m a , from 0.6 n g / m l to 26 n g / m l ; a n d 1 with islet cell c a r c i n o m a , 22 ng/ml. T h e r e was no.statistical difference in serum CEA levels a m o n g various histologic types of p a n c r e a t i c cancer. All of the patients whose serum CEA levels were above 20 n g / m l h a d h e p a t i c metastasis. 3) Serum CEA levels of p a n c r e a t i c cancer: its relation to sites Serum CEA levels r a n g e d from 3.7 n g / m l to 22 n g / m l ( m e a n ___ SD, 11+7.9) for t u m o r s which occupied all p a r t s of the pancreas, from 0.6 n g / m l to 34 n g / m l (9+11.6) for t u m o r s

which o c c u p i e d only the h e a d o f the pancreas, a n d from 1.1 n g / m l to 36 n g / m l (10.8_+9.6) for tumors which o c c u p i e d both body a n d tail of the pancreas. T h e r e was no statistical difference in serum CEA levels in relation to various sites of the p a n c r e a t i c cancer (Fig. 3). 4) Clinical course T h e first case is a 49-year-old m a n who was a d m i t t e d because of a b d o m i n a l pain. This was later diagnosed as p a n c r e a t i c cancer in its b o d y a n d tail by u l t r a s o n o g r a p h y , scintigram a n d a n g i o g r a p h y o f the a b d o m e n . Surgery was p e r f o r m e d . Preoperatively, his serum GEA level was 5.6 n g / m l b u t RNase was within n o r m a l limits. After the o p e r a t i o n CEA levels

April 1979

125

Clinical Studies on Carcinoembryonic tlntigen in Pancreatic Cancer

once decreased b u t g r a d u a l l y increased again as his clinical condition b e c a m e worse. In this case, serum CEA levels were useful for detecting early cancer of the p a n c r e a s a n d evaluating progress of the disease (Fig. 4). T h e second case is a 55-year-old m a n who was a d m i t t e d because of diabetes mellitus a n d severe a b d o m i n a l p a i n . It was diagnosed as p a n c r e a t i c cancer by endoscopic r e t r o g r a d e

Clinical

T.O. 49 years Operation

Course

J,

Anticancer

I Ncs

~Fu

200mg[

therapy

Abdominal pain

~.:.'#";" ,~i~'.'.':':.

Diarrhea

.....'.

Ai-Phos Arnylase

p a n c r e a t o g r a p h y a n d a n g i o g r a p h y . He und e r w e n t an o p e r a t i o n , b u t the t u m o r was not resectabte because o f c a n c e r invasion to the p o r t a l vein. D u r i n g the o p e r a t i o n , no h e p a t i c metastasis was observed. Serum C E A was 0.6 n g / m l . After the o p e r a t i o n he was given anticancer medications, b u t his c o n d i t i o n b e c a m e worse a n d the patients d i e d on the ninetieth hospital day. Serum C E A g r a d u a l l y increased

: ::::::

: :::

107 128

90 137

.. 9 :

. ....

:

::i: i ::

:. :.

9

. .

]

Futraful

~0m 9/day

....... -..

, .

88 106

.....

.

70 92

.

i: i

............... :." :.:.:.:.:..:.'

65

95 15

500

145 80

CEA (ng/ml)

60

30

Fig. 4.

Clinical Course

H,N.

90

180 days

Clinicalcourse (case 1).

55 years

~$

Futraful 400rag/day

Anticar~er

150

120

t" I

~ ~ / d a y

NCS 2000J/day

therapy

:'i :::i.: : :':'..! :"

Back pain CRP

-

LDH

+

2)5 107

Amylase

i; .:.:" : : ".': : :.': i!! :::: : "i'.:!'!:!::!i:"!': ::" ! "::i:ii!:i::i] 3+

4+

+

+

22I 40

175 45

30

60

2+

305

CEA (ng/ml) 5 2.5

Fig. 5.

Clinical course (case 2).

9O days

126

Vol. 14, No. 2

T. Y A M A U C H I E T A L .

RNese U

r - - 0.407 ( n- 3O) p(O.05

500

0

%

0

150

t~

01! 2.5

Fig. 6.

10

20

3o

40 nglml

c~ Correlation of CEA and RNase in pancreatic cancer. 9 hepatic metastasis (S) no hepatic metastasis

a n d r e a c h e d the m a x i m u m of 3 n g / m l at his death. At autopsy the t u m o r was f o u n d in the body a n d tail a n d some h e p a t i c metastasis were found (Fig. 5). 5) RNase a n d C E A in p a n c r e a t i c c a n c e r W e studied the correlation between the level of CEA a n d the level o f R N a s e in p a n c r e a t i c cancer. W e c o n f i r m e d a positive c o r r e l a t i o n (p