Colorectal neoplasms and smoking; a case-control study

April 1995

DIMINUTIVE POLYPS AT SCREENING FLEXIBLE SIGMOIDOSCOPY REMAIN AN IMPORTANT INDICATION FOR C O L O N O S C O P Y

H.W.Olsen and W.A. Lawrence, Oakland, California In our series of 1441 patients who have undergone colonoscopy and polypectomy 501 patients were referred because of at least one polyp at flexible sigmoidoscopy. A subgroup of 241 patients were completely asymptomatic. One hundred and five of these patients had only diminutive polyps within the 60 cm range o f flexible sigmoidoscope. In this group we found 31% to have polyps beyond 60 cm including 8 patients with medium sized polyps (.6 -.9 cm), and 7 advanced lesions one of which included a colon cancer. All 7 patients with advanced lesions including the cancer were older than 65 years of age. Although the above incidence for cancer and advanced lesions beyond the sigmoid is 50% less in this subgroup than seen in our whole population, the results suggest that we cannot consider diminutive polyps at sigmoidoscopy insignificant enough to not recommend colonoscopy. A final concern from this study is the observation that fewer than 30% of the patients referred for colonoscopy with polyps at screening sigmoidoscopy are women when in fact the incidence of polyps and cancer are roughly equivalent. This coupled with the observation that women in our population accounted for 62% of the Dukes' C cancers suggests the need to further encourage women to undergo screening sigmoidoscopy.

C A N C E R C E L L M O R P H O L O G Y AT THE I N V A S I V E F R O N T AND E X P R E S S I O N OF C E L L A D H E S I O N - R E L A T E D C A R B O H Y D R A T E IN THE P R I M A R Y L E S I O N OF C O L O R E C T A L C A N C E R WITH L I V E R M E T A S T A S I S . M.Ono, M . S a k a m o t o , T . S a w a d a , S . H i r o h a s h i , T.Muto. Dept. of Surgery, U n i v e r s i t y of Tokyo, P a t h o l o g y Div., N a t i o n a l C a n c e r C e n t e r R e s e a r c h Institute, Tokyo, J a p a n Background: Liver metastasis of c o l o r e c t a l cancer is an important problem in surgical t r e a t m e n t and p r o f o u n d l y a f f e c t s the p r o g n o s i s of patients. If we can identify characteristic f i n d i n g s in the p r i m a r y l e s i o n s t r o n g l y r e l a t e d to liver m e t a s t a s i s , t h o s e can be u s e d for p r o g n o s t i c m a r k e r s of liver m e t a s t a s i s . In s e a r c h of t h e m we investigated the p r i m a r y lesion of c o l o r e c t a l c a n c e r with liver m e t a s t a s i s . M e t h o d s : G r o u p A was a coloreetal c a n c e r g r o u p with s y n c h r o n o u s l i v e r m e t a s t a s e s and g r o u p B with o n l y lymph n o d e m e t a s t a s e s w i t h o u t r e c u r r e n c e for five years. B o t h g r o u p s c o n s i s t e d of 24 oases. We focused on c a n c e r cell m o r p h o l o g y at i n v a s i v e front a n d e x p r e s s i o n of s i a l y l - L e w i s X (sLe(X)) on the p r i m a r y c o l o r e c t a l cancer. R e s u l t s : F o c a l l y d e d i f f e r e n t i a t e d c a n c e r cells w i t h s i n g l e or s o l i t a r y t r a b e c u l a r form showing i n f i l t r a t i n g g r o w t h p a t t e r n at i n v a s i v e front were f r e q u e n t l y f o u n d in g r o u p A. The m o r p h o l o g y was termed "focal dedifferentiation". Eleven severe "focal d e d i f f e r e n t i a t i o n " cases (46%) were found in g r o u p A, but o n l y one (4%) in g r o u p B. (p=0.001) On e x a m i n a t i o n of the whole cancer, sLe(X) s t a i n i n g was p o s i t i v e in t w e l v e cases (50%) in g r o u p A, but o n l y t h r e e (13%) in g r o u p B. (p=0.011) W h e n the t w o f i n d i n g s a b o v e were c o m b i n e d , "focal dediff e r e n t i a t i o n " p o s i t i v e for sLe(X) s t a i n i n g was 17 c a s e s (71%) in g r o u p A, w h i l e o n l y four (17%) in g r o u p B. (p=0.00O4) C o n c l u s i o n s : B o t h "focal d e d i f f e r e n t i a t i o n " and e x p r e s s i o n of sLe(X) a n t i g e n in the p r i m a r y l e s i o n are c o n s i d e r e d good markers for a s s e s s i n g the m e t a s t a t i c a b i l i t y of c o l o r e c t a l cancer.

Gastrointestinal Oncology A521

• COLORECTAL N E O P L A S M S A N D SMOKING; A CASE-CONTROL STUDY. F. Omata, F. Ueno, H. Ide, Y. Shibayama, H. Takahashi. Department of Medicine, TokaJ University Oiso Hospital, Oiso, Kanagawa, Japan. Several studies have indicated a possible association b e t w e e n s m o k i n g a n d t h e o c c u r r e n c e of color e c t a l n e o p l a s m s , b u t o t h e r s t u d i e s f a i l e d to conf i r m t h i s a s s o c i a t i o n . T h e p u r p o s e of t h i s s t u d y is to d e t e r m i n e w h e t h e r s m o k i n g is a risk f a c t o r for colorectal neoplasms, including benign adenomas. METHODS: A case-control study was undertaken in 539 p a t i e n t s w h o u n d e r w e n t t o t a l c o l o n o s c o p y a n d in whom the history of smoking was investigated. F i n d i n g s of c o l o n o s c o p y , c o m b i n e d w i t h histopathological findings, s e r v e d as the c r i t e r i o n s t a n d a r d to measure m a i n o u t c o m e , p r e s e n c e or absence of carcinomas and adenomas. Cases consisted of 103 p a t i e n t s ; 97 w i t h a d e n o m a s , ii w i t h c a r c i n o m a s and 5 with both carcinomas and adenomas. Controls were 436 subjects without colorectal neoplasms, Those with k n o w n risk f a c t o r s for c o l o r e c t a l .ineoplasms were excluded. Logistic regression analysis were c o n d u c t e d u t i l i z i n g age a n d sex as c o v a r i a t e s . RESULTS: The m e a n age of 103 patients ~ (Male:Fem a l e = 7 4 : 2 9 ) w i t h c o l o r e c t a l n e o p l a s m s w a s 58 years old, whereas the mean age of 436 controls ( M a l e : F e m a l e = 2 3 2 : 2 0 4 ) w a s 48 y e a r s old. O d d s ratio of smokers for colorectal neoplasms ;was 1.16 (95%Confidence interval 0.69-I.92).(P>0.05) Furt h e r m o r e , t h e d a t a w a s a n a l y z e d a c c o r d i n g to sex, a g e a n d t o t a l s m o k i n g a m o u n t (TSA) (the m e a n n u m b e r of cigarettes/day X smoking period [years]). The odds r a t i o w a s 1.19 in male, 1.01 in female. The odds r a t i o w a s 0.63 if a g e w a s u n d e r 50, 1.20 if age w a s b e y o n d 50. T h e o d d s r a t i o w a s 0.86 if TSA w a s u n d e r 500, 1.49 if T S A w a s b e y o n d 500, 1.79 if T S A w a s b e y o n d i000. C O N C L U S I O N S : No s t a t i s t i c a l l y s i g n i f i c a n t a s s o c i a tion was observed between smoking and colorectal n e o p l a s m s t h o u g h o d d s r a t i o w a s apt to i n c r e a s e as age and total smoking amount increased.

ROLE OF ACTIN AND MYOSIN ON COLONIC CANCER CELL MIGRATION. K. Otaka, S Watanabe, R. Iwazaki, M. Hirose, N Sato Dept. of G a s t r o e ~ Juntendo Univ School of M e d Tokyo, Japan The mechanism of cancer cell metastasis involves cell migration which might be modulated by cytoskeleton, extracellular matrix and growth factors. However, the detail metastasis is still unclear. Therefore, we recently established a new simple and convenient model to analyze the cancer cell metastasis using human gastric cancer ce l ne. Us ng th s model, we assessed the migration capacity of colonic cancer cell lines(differentiated adenocarcinoma SW837, undifferentiated adenocarcinoma SW620) and also assessed the effects of actin inhibitor, cytochalasin B(CB) and myosin light chain kinase inhibitor, wortmannin (WO). METHOD: SW620 and SW837 cells (3.5XI0 ~ cells) were inoculated into the round enclosed area (diameter,15mm) by silicon fence in a plastic culture dish and cultured in L-15 medium with 10% FBS.Inoculated cells formed round shaped ceil sheet in 24h and subsequently silicon fence was removed and the cancer cell migration was monitored .The number of migrated cells in a unit area of free space was counted after 48 h . Effects o f CB(l-100ll M) and W O ( l - 1 0 0 l l M) were assessed The cell proliferation was detected using BrdU staining. RESULT:After the removal of the fence, cancer cells started to migrate independently and spread to all direction from the edge of the cell sheet The number o~" cancer cells migrated from the cell sheet 48h after the start of mi was presented in a table. ram:distance from the edge of cell sheet -5mm

5-10

I0-15

15-20

20-25

25-30

10283

746.8

562.5

320.8

299

213.3

CBIO01~ M

255*

248*

237*

340*

317"

WOl00/z M

5295*

358.9*

303*

245.5*

2385*

1605

SW837control

971.4

599.5

4834

385.3

2804

2184

CBI001~ M

294.2*

198.8'

1798"

157.9"

1443"

109.4

SW620 control

228

W O I 0 0 II M 387.3* 299* 101.2" 56.3* 62.3* 33.5 There were no differences in migrated cell number between SW620 and SW837. Spontaneous cell migration and proliferation were significantly inhibited by CB and WO in both cell lines in a dose dependent manner CONCLUSION:A newly established cancer metastasis model was very useful for the analysis for colonic cancer cell migration and proliferation as well as a gastric cancer cell line The integrily of the cytoskeletal system plays an important role in not only gastric cancer cells but also in colonic cancer cells.