T i t l e Page
T e c h n i c a l Note
Development o f r e p e a t a b l e m i c r o c a t h e t e r a c c e s s p o r t f o r i n t r a a r t e r i a l t h e r a p y o f l i v e r cancer
Y a s u s h i Fukuoka MS ( l l , T o s h i h i r o Tanaka 孔 I D ,PhD ( l l , H i d e y u k i N i s h i o f u k u MD, PhD ( l l , T a k e s h i S a t o MD(!)' T e t s u y a Masada M D ( l l , S h o t a T a t s u m o t o M D C I J , Nagaaki Marugami MD, PhD ( l l , H i r o s h i S a k a g u c h i M D PhD < 2 l , Kimihiko Kichikawa MD, PhD
CI)( 1 ) D e p t . o f R a d i o l o g y , Nara M e d i c a l U n i v e r s i t y , K a s h i h a r a , J a p a n ( 2 ) D e p t . of R a d i o l o g y , Minaminara M e d i c a l C e n t e r , Oyodo , J a p a n
C o r r e s p o n d e n c e t o :
T o s h i h i r o T a n a k a , M D , PhD
Department of R a d i o l o g y , Nara M e d i c a l Uni v e r s i t y 840 S h i j o
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Acknowledgment:
We t h a n k D r . Shunsuke Shimamura and D r . Terumasa S h i m a d a , V e t e r i n a r y M e d i c a l C e n t e r , Osaka P r e f e c t u r e U n i v e r s i t y f o r s u p p o r t i n t h i s a n i m a l s t u d y .
We t h a n k Ms. Marian Pahud f o r a d v i c e i n s u b m i t t i n g t h i s a r t i c l e .
T h i s work was s u p p o r t e d by G r a n t ‑ i n ‑ A i d f o r S c i e n t i f i c R e s e a r c h ( C ) , 15K0996 7 .
Key w o r d s ,
T r a n s a r t e r i a l c h e m o e m b o l i z a t i o n , H e p a t i c a r t e r i a l i n f u s i o n ch e m o t h e r a p y , I m p l a n t a b l e p o r t
S h o r t T i t l e ,
Repeatable m i c r o c a t h e t e r a c c e s s p o r t
O r i g i n a l S u b m i s s i o n
・B l i n d e dM a n u s c r i p t C l i c k h e r e t o v i e w l i nked R e f e r e n c e s 三
1 2 3 4 5 6 7 8 9
A b s t r a c t Purpose
To d e v e l o p an i m p l a n t a b l e p o r t i n which a m i c r o c a t h e t e r can be i n s e r t e d f o r a c o m b i n a t i o n t h e r a p y 1 O 1 of r e p e a t e d t r a n s a r t e r i a l c h e m o e m b o l i z a t i o n (TACE) and h e p a t i c a r t e r i a l i n f u s i o n c h e m o t h e r a p y
2 ペ ペ ? 4 5 6 7 9 8 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 7 6 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3
4 5
1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 6
(HAIC) f o r a d v a n c e d l i v e r c a n c e r . M a t e r i a l s and Methods
The d e s i g n o f a c u r r e n t l y u s e d i m p l a n t a b l e p o r t was m o d i f i e d . A f u n n e l p
ぽtwas c o n s t r u c t e d i n t h e p o r t . The s e p
印m w
出p u n c t u r e d by a 20
・gaugei n d w e l l i n g n e e d l e and 2 . 0
・Frn o n ‑ t a p e r e d m i c r o c a t h e t e r was i n s e r t e d i n t o t h e p o r t . I n i n v i t r o s t u d i e s , t h e e x t r a c t i o n o f t h e m i c r o c a t h e t e r 合 omt h e p o r t t 祉 ought h e f u n n e l p a r t was e v a l u a t e d . A 5
・F ri n d w e l l i n g c a t h e t e r c o n n e c t e d t o t h e p o r t
W出p l a c e d i n a v a s c u l a r model and a m i c r o c a t h e t e r c a t h e r i z a t i o n was e v a l u a t e d . I n an i n v i v o s t u d y , t h e p o r t
『c a t h e t e r s y s t e m was i m p l a n t e d i n t h e h e p a t i c a r t e r y i n a p i g . A m i c r o c a t h e t e r was p e r c u t a n e o u s l y i n s e r t e d t h r o u g h t h e p o r t i n t o t h e hep a t i c a r t e r i a l b r a n c h e s .
R e s u l t s
I n t h e i n v i t r o s t u d i e s , t h e m i c r o c a t h e t e r was s m o o t h l y e x t r a c t e d t h r o u g h t h e p o r t and c a t h e t e r i z a t i o n s i n t o t h e hep a t i c a r t e r i e s we r e s u c c e s s 白 l v i a a l l 7 d i f f e r e n t septum p u n c t u r e s i t e s . I n t h e i n v i v o s t u d y , r e p e a t e d s e l e c t i v e TACE t h r o u g h t h e p o r t w a s s u c c e s s f u l l y c o n d u c t e d on 7 ,
1 4 and 2 1 d a y s a f t e r t h e i m p l a n t a t i o n . C o n c l u s i o n
T he d e v e l o p e d i m p l a n t a b l e p o r t can be used f o r r e p e a t e d c a t h e t e r i n s e r t i o n i n t o t h e h e p a t i c a r t e r y . The c o m b i n a t i o n of r e p e a t e d TACE and HAIC c o u l d be pos s i b l e u s i n g t h i s d ev i c e .
1
1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3
4
5 6 7 8 9 0 1 2 3 4 5 67890123456789nu
− − 2 3 4 5 6 7 8 9 0 1 2 3 4 5 1 1 1 1 1
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1 1 41112
2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 6
I n t r o d u c t i o n
T h e r e a r e v a r i o u s t r e a t m e n t o p t i o n s i n i n t r a a r t e r i a l t h e r a p y f o r a d v a n c e d l i v e r c a n c e r [ 1 , 2 ] . T r a n s a r t e r i a l c h e m o e m b o l i z a t i o n (TACE) u s i n g d r u g e l u t i n g m i c r o s p h e r e s i s w i d e l y p e r f o r m e d i n l i v e r m e t a s t a s e s , i . e . c o l o r e c t a l c a n c e r (mCRC) [ 3 , 4 ) . H e p a t i c a r t e r i a l i n f u s i o n c h e m o t h e r a p y (HAIC) i s a l s o an e 百 e c t i v et r e a t m e n t お rmCRC [ 5 ‑ 7 ] .
I n g e n e r a l , f o r a d v a n c e d l i v e r c a n c e r s , r e p e a t e d TACE i s r e q u i r e d . P r e v i o u s r e p o r t s showed t h a t TACE u s 出 gi r i n o t e c a n e l u t i n g m i c r o s p h e r e s a r e p e r f o r m e d 2 t o 5 t i m e s i n mCRC p a t i e n t s [ 8 ] . Longer r e p e a t e d TACE p e r i o d c o u l d i m p r o v e t h e o v e r a l l s u r v i v a l d u r a t i o n [ 9 ] . T h e r e f o r e , s m a l l e r o r b i o d e g r a d a b l e m i c r o s p h e r e s h a v e b e e n i n n o v a t e d t o i m p r o v e t h e r e p e a t a b i l i t y ofTACE [ l 0
・1 5 ] .
A f t e r a c h i e v i n g a t u m o r r e s p o n s e u s i n g TACE, e f f e c t i v e m a i n t e n a n c e c h e m o t h e r a p y i s r e q u i r e d . A l t e r n a t i v e t r e a
加i e n t so f TACE and c h e m o t h e r a p i e s may a l s o be e f f e c t i ve . However , many p a t i e n t s who a r e r e c e i v i n g TACE h a v e a l r e a d y been r e f r a c t o r y t o s t a n d a r d s y s t e m i c c h e m o t h e r a p i e s [ 1 6 , 1 7 ] . I n s u c h a s i
加a t i o n ,HAIC m i g h t b e p r o m i s i n g t o s u p p r e s s
加mor r e g r o w t h a f t e r TACE.
To p e r f o r m c o m b i n a t i o n t r e a t m e n t s o f r e p e a t e d TACE and HAIC, a r e p e a t a b l e m i c r o c a t h e t e r a c c e s s p o r t was d e v e l o p e d . H e r e i n t h e i n v i t r o and i n v i v o e x p e r 出 i e n t a lr e s u l t s u s i n g t h i s d e v i c e a r e s h o w n .
M a t e r i a l s a n d Methods
Con c e p t and d e v e l o p m e n t of r e p e a t a b l e m i c r o c a t h e t e r α c c e s s p o r t
The d e s i g n o f a c u r r e n t l y u s e d p o r t was m o d i f i e d . T h i s d e v e l o p e d p o r t was c o n s t r u c t e d i n t h r e e p a r t s , a b o d y , a f u n n e l and a c a p . A s i l i c o n s e p t u m was i n s e r t e d i n t o t h e c a p p a r t . The d i a m e t e r o f t h e s e p t u m was s e t 15mm f o r a n e e d l e t o e a s i l y punc t u r e t h e s e p t u m . The s l o p e o f t h e
2
2 3 4 5
6 78 9 10
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23 24 25 262 7
2829
3031
3233
343 5
3637 3 8 39
40 41 42 4344
45 46 47 48 4950 51
5253
5455
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f u n n e l was s e t a t a 6 0 ° a n g l e f o r a m i c r o c a t h e t e r t o s m o o t h l y s l i d e a l o n g t h e f u n n e l w a l l t o t h e b o t t o m ( F i g 1 ) . The s u r f a c e o f an i n n e r lumen o f t h e f u n n e l p a r t was c a r e f u l l y p o l i s h e d t o p r e v e n t s t a c k o f a m i c r o c a t h e t e r by a p o l i s h m a c h i n e (SMAP, Toyo Kenmazai Kogyo L t d . , T o k y o , J a p a n ) . A20
・g a u g ei n d w e l l i n g n e e d l e c o n s i s t i n g of a n i n n e r n e e d l e a n d o u t e r c y l i n d e r n e e d l e was u s e d f o r t h e p u n c t u r e o f t h e s e p
加mo f t h e p o r t a l l o w i n g f o r a 2 . 0 ‑ F r m i c r o c a t h e t e r t o b e i n s e r t e d .
I n v i t r o e v αl u a t i o n
F i r s t l y , e x t r a c t i o n of a m i c r o c a t h e t e r t h r o u g h t h e p o r t w
出t e s t e d . A t o t a l o f 7 p u n c t
旧es i t e s were s e l e c t e d on t h e s e p
加m,c e n t e r , and 2mm a n d 4mm c o n c e n t r i c a l l y from t h e c e n t e r ( F i g 2 ) . The s e p t u m was punc
加r e dv e r t i c a l l y by a 20
・g a u g ei n d w e l l i n g n e e d l e ( S u r f l o ; T e r u m o , To 匂 r o , J a p a n ) . Af 王 e rr e m o v a l o f t h e i n n e r n e e d l e , a c o m m e r c i a l l y a v a i l a b l e 2 . 0 ‑ F r n o n ‑ t a p e r e d m i c r o c a t h e t e r (C
訂n e l i a nM a r v e l , Tokay M e d i c a l P r o d u c t , K a s u g a i , J a p a n ) w i t h an 0 . 0 1 4
・i n c h g u i d e w i r e (GT w i r e , T e r u m o ) was i n s e r t e d i n t o t h e p o r t . The s u c c e s s r a t e o f t h e m i c r o c a t h e t e r w i t h a g u i d e w i r e which was p a s s e d t h r o u g h t h e f u n n e l p a r t a n d e x t r a c t e d f r o m t h e p o r t was e v a l u a t e d .
S e c o n d l y , a 5
・F rc a t h e t e r w i t h a s i d e h o l e was p l a c e d i n a v a s c u l a r m o d e l . The t i p of t h e c a t h e t e r was i n s e r t e d i n t o t h e g a s t r o d u o d e n a l a r t e r y a n d t h e s i d e h o l e was p o s i t i o n e d i n t h e common h e p a t i c a r t e r y . The p r o x i m a l e n d o f t h e c a t h e t e r was c o n n e c t e d t o t h e d e v e l o p e d p o r t . A m i c r o c a t h e t e r was i n s e r t e d i n t o t h e p o r t a t e a c h o f t h e 7 punc
何 回s i t e sa n d t h e t i p o f t h e m i c r o c a t h e t e r was 吋 e c t e d
合omt h e s i d e h o l e . T h e n , t h e m i c r o c a t h e t e r was i n s e r t e d i n t o t h e r i g h t a n d l e f t h e p a t i c a r t e r i e s ( F i g 3 ) . The s u c c e s s r a t e of t h e s e l e c t i v e i n s e r t i o n of t h e m i c r o c a t h e t e r i n t o t h e h e p a t i c a r t e r i a l b r a n c h was e v a l u a t e d .
5
s I n v i v o e v a l u a t i o n 59
60
61 3
62 63 64 65
1 2
3 The s t u d y was p e r f o r m e d a t V e t e r i n a r y M e d i c a l C e n t e r , Osaka P r e f e c t u r e U n i v e r s i t y , J a p a n . 4
5 6 7 8 9 0 1 2 3
4
5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0
1
2 3 4 5 6 7 8 9 0
1
2 3
4 5
6 7 8 9 0 1 2 3 4 5 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 6
The s t u d y p r o t o c o l w
出a p p r o v e dby t h e S t a t e Committee o f Osaka P r e f e c t u r e U n i v e r s i t y . One p i g w e i g h i n g 5 5 kg was u s e d . A f t e r i n t r a m u s c u l a r p r e m e d i c a t i o n a t r o p i n e and k e t a m i n e , a n e s t h e s i a w
出i n d u c e dby i n t r a v e n o u s i n e c t i o n o f d i l u t e d p e n t o b a r b i t a l . The a n i m a l was o r o t r a c h e a l l y i n t u b a t e d and m e c h a n i c a l l y v e n t i l a t e d w i t h an ox yg e n ‑ a i r m i x t u r e c o n t a i n i n g h a l o t h a n e .
The r i g h t i l i a c a r t e r y was e x p o s e d v i a a s u r g i c a l c u t ‑ d o w n a n d a 4
・F rs h e a t h ( H a n a k o M e d i c a l , To 匂叫 J 叩 an)w
出i n t r o d u c e d .A 4 ‑ F r c o b r a ‑ s h a p e d a n g i o g r a p h i c c a t h e t e r (Hanako M e d i c a l ) wa s i n s e r t e d i n t o t h e c e l i a c
仕切l k ,and a c e l i a c a n g i o g r a m was o b t a i n e d . A 2 . 5
・F r ,1 0 5
・c m ‑ l o n g m i c r o c a t h e t e r ( R e n e g a d e , B o s t o n S c i e n t i f i c , Ma r l b o r o u g h , USA) w 出 回 s e r t e d i n t o t h e g a s t r o d u o d e n a l
紅 白r y .A 0 . 0 1 8 ‑ i n c h , 205‑cm s t i f f g u i d e w i r e ( R a i n b o w , P i o l a x M e d i c a l D e v i c e s , Yokohama, J a p a n ) was i n s e r t e d t h r o u g h t h e m i c r o c a t h e t e r . Then , t h e whole s y s t e m , i n c l u d i n g t h e s h e a t h , t h e a n g i o g r a p h i c c a t h e t e r , and t h e m i c r o c a t h e t e r , was r e p l a c e d b y a n a n t i c o a g u l a n t ‑ c o a t e d i n d w e l l i n g c a t h e t e r , w i t h a 5 ‑ F r p r o x i m a l s h a f t and a 2 . 7
・F rd i s t a l s h a f t ( A n t h r o n PU c a t h e t e r , T o r a y M e d i c a l , Urawa, J a p a n ) . A s i d e h o l e a p p r o x i m a t e l y 3mm i n s i z e was c r e a t e d w i t h s c i s s o r c u t a t t h e t r a n s i t i o n zo ne f r o m t h e s h a f t t o t h e t a p e r e d t i p . The c a t h e t e r t i p was i n s e r t e d i n t o t h e d i s t a l g a s t r o d u o d e n a l a r t e r y and t h e s i d e h o l e w
出p o s i t i o n e d a t t h e common h e p a t i c a r t e r y . A 2 . 5
・F r m i c r o c a t h e t e r
W出i n s e r t e di n t o t h e g a s t r o d u o d e n a l a r t e r y t h r o u g h t h e s i d e ‑ h o l e and m i c r o ‑ c o i l s ( T o r n a d o ; Cook , B l o o m i n g t o n , USA) w e r e p l a c e d t o f i x t h e i n d w e l l i n g c a t h e t e r . F i n a l l y , a t t h e r i 凶 ti n g u i n a l r e g i o n , a U ‑ s h a p e d s u b c u t a n e o u s t u n n e l was c r e a t e d up from t h e i l i a c a r t e r i a l punc
加r es i t e . The p r o x i m a l e n d of t h e c a t h e t e r was c o n n e c t e d t o t h e d e v e l o p e d p o r t embedded u n d e r t h e s k i n .
A f t e r t h e i m p l a n t a t i o n o f t h e p o r t ‑ c a t h e t e r s y s t e m , t h e p o r t was p u n c t u r e d p e r c u t a n e o u s l y by a20
・g a u g e n e e d l e , and a 2 . 0
・F r n o n ‑ t a p e r e d m i c r o c a t h e t e r w i t h a 0 . 0 1 4 ‑ i n c h g u i d e w i r e w
出4
2
3
i n t r o d u c e d i n t o t h e p o r t . The m i c r o c a t h e t e r was i n s e r t e d i n t o t h e h e p a t i c a r t e r i a l b r a n c h i n a 4
5 6 7 8 9
s e g m e n t a l l e v e l s e l e c t i v e l y and l i p i o d o l e m u l s i o n was i n i e c t e d . R e p e a t e d TACE was p e r f o r m e d e v e r y week f o r 3 weeks .
n o
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0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 6
R e s u l t s
A c c e s s i b i l i t y of αm i c r o c α t h e t e r t h r o u g h t h e p o r t
I n t h e f i r s t p a r t of t h e i n v i t r o s t u d y , t h e m i c r o c a t h e t e r was e x t r a c t e d t h r o u g h t h e f u n n e l p a r t v i a a l l 7 punc
回r es i t e s . I n t h e s e c o n d p a r t , i n a l l 7 punc
加r es i t e s , t h e m i c r o c a t h e t e r was 司 e c t e dv i a t h e s i d e ho l e and was i n s e r t e d i n t o t h e l e
食andr i g h t h e p a t i c a r t e r i e s of t h e v a s c u l a r m o d e l .
F e a s i b i l i t y of s e l e c t i v e TACE t h r o u g h t h e p o r t
The c a t h e t e r ‑ p o r t s y s t e m was s u c c e s s f u l l y p l a c e d i n t o t h e p i g . On day 7 a f t e r t h e p o r t ‑ c a t h e t e r s y s t e m i m p l a n t a t i o n , t h e p i g was c a r r i e d t o t h e a n g i o
同room and a h e p a t i c a r t e r i o g r a p h y was o b t a i n e d v i a t h e p o r t ( F i g 4 ) . T h e n , a r n i c r o c a t h e t e r was i n s e r t e d p e r c u t a n e o u s l y t h r o u g h t h e p o r t . The t i p of t h e m i c r o c a t h e t e r was e x t r a c t e d t h r o u g h t h e s i d e ‑ h o l e and s e l e c t i v e l y i n s e r t e d i n t o t h e l e f t h e p a t i c a r t e r y . During t h e c a t h e r i z a t i o n p r o c e d u r e , no b l e e d i n g o c c u r r e d be s i d e t h e i n s e r t e d m i c r o c a t h e t e r . E m b o l i z a t i o n w i t h an e m u l s i o n of l i p i o d o l 4mL and c o n t r a s t m a t e r i a l 2mL was p e r f o r m e d i n t h e l e f t l a t e r a l s e g m e n t . A f t e r t h e TACE p r o c e d u r e , t h e m i c r o c a t h e t e r was removed and h e p a r i n a t a d o s e of2 . 5 mL was i n i e c t e d i n t h e p o r t
圃c a t h e t e r s y s t e m . The p i g was moved t o a CT room and a CT s c a n was o b t a i n e d t o c o n f i r m t h e e m b o l i z a t i o n
訂e a . T h i s p r o c e d u r e was s u c c e s s f u l l y r e p e a t e d . The r i g h t a n t e r i o r and m i d d l e h e p a t i c a r t e r i e s were e m b o l i z e d on d a y s 1 4 and 2 1 , r e s p e c t i v e l y ( F i g 5 ) .
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P r e v i o u s l y , I t a n o e t a l . r e p o r t e d t h e i r d e v e l o p m e n t of a m i c r o c a t h e t e r a c c e s s i b l e s y s t e m , S y s t e m ‑ i , i n which a l a t e x r u b b e r c a p was c o n n e c t e d t o an i n d w e l l i n g 5
・Frc a t h e t e r and s u b c u t a n e o u s l y i m p l a n t e d [ 1 8 ] . I n t h e i r s y s t e m , t h e r u b b e r c a p had t o be p u n c t u r e d f o r t h e m i c r o c a t h e t e r i n s e r t i o n , which w
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加r e d i r e c t i o n was p a r a l l e l t o t h e s k i n . To overcome t h e d i
伍c u l t yof t h e punc
加r e ,t h e s h a p e and d e s i g n of o u r d e v i c e was m o d i f i e d b a s e d on c u r r e n t l y u s e d c e n t r a l v e n o u s o r a r t e r i a l po r t s . The t o p of t h e p o r t can be e a s i l y p u n c t u r e d v e r t i c a l l y t o t h e s k i n . Th e septum w i t h l 5mm i n d i a m e t e r a l s o a l l o w e d a n e e d l e t o b l i n d l y h i t .
I n t h e c o n s t r u c t i o n of t h i s p o r t , t h e s h a p e o f t h e f u n n e l p
釘t was p a r a m o u n t . A m i c r o c a t h e t e r i n s e r t e d t h r o u g h t h e septum must be e x t r a c t e d s m o o t h l y from t h e p o r t . Th e p e r i p h e r a l punc
加r e s i t e i n t h e septum c o u l d make i t be d i f f i c u l t . However, t h e e x t r a c t i o n of a m i c r o c a t h e t e r w
出s u c c e s s f u l v i a e v e r y p u n c t u r e s i t e . The f u n n e l w i t h a s t a n d a r d a n g e l of 6 0 ° c o u l d be o p t i m a l f o r a m i c o c a t h e t e r t o s l i d e t o t h e b o t t o m . The 18mm h e i g h t o f t he p o r t w
出b a s e do n t h e r a t i o of t h e d i a m e t e r o f t h e septum t o t h e a n g l e of t h e f u n n e l . T h i s h e i g h t c o u l d be a c c e p t a b l e f o r s u b c u t a n e o u s i m p l a n t a t i o n .
The i n v i t r o s t u d y show e d t h e f e
ぉi b i l i t y of t h e r e p e a t e d s e l e c t i v e TAC E . T h e m i c r o c a t h e t e r
W出
s u c c e s s f u l l yi n s e r t e d v i a t h e p o r t and s e l e c t i v e c a t h e t e r i z a t i o n was p e r f o r m e d e v e r y week f o r 3 w e e k s . No b l e e d i n g o c c u r r e d t h r o u g h t h e n e e d l e p u n c t u r e s i t e . The s y s t e m w a s n o t o b s t r u c t e d d u r i n g t h e o b s e r va t i o n p e r i o d . I n t h i s p i g s t u d y , t h e i l i a c a r t e r y w a s expo s e d v i a a s u r g i c a l c u t ‑ down t o p r e v e n t k i n k i n g of t h e c a t h e t e r due t o any l e g movement. I n c l i n i c a l p r a c t i c e , p e r c u t a n e o u s c a t h e t e r i n s e r t i o n t e c h n i q u e w a s e s t a b l i s h e d w i t h o u t any d i f f i c u l t i e s i n HAIC u s i n g t h e p o r t ‑ c a t h e t e r s y s t e m.
The con c e p t of t h i s d e v i c e i s t o p e r f o r m r e p ea t e d T ACE and a l s o t o p e r f o r m HAIC.
I n t e r m i t t e n t tumor v olume r e d u c t i o n c o u l d b e a c h i e v e d b y t h e r e p e a t e d s e l e c t i ve o r n o n ‑ s e l e c t i v e
6
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TACE and m a i n t e n a n c e t h e r a p y by HAIC c o u l d s u p p r e s s t
凶n o rr e g r o w t h . The e f f i c a c y of t h i s c o m b i n a t i o n must be e v a l u a t e d i n c l i n i c a l s t u d i e s .
When HAIC i s p e r f o r m e d i n p a t i e n t s w i t h a n a t o m i c a l v a r i a t i o n s of t h e h e p a t i c a r t e r y , i . e . t h e r e p l a c e d r i g h t a r i s i n g from t h e s u p e r i o r m e s e n t e r i c a r t e r y , t h e p r o x i m a l s i t e of t h e r e p l a c e d h e p a t i c arteηis e m b o l i z e d w i t h c o i l s and a s i n g l e p o r t ‑ c a t h e t e r i s p l a c e d i n t h e main h e p a t i c a r t e r y [ 1 9 , 2 0 ] . However , a f t e r t h e e m b o l i z a t i o n , a m i c r o c a t h e t e r c a n n o t be i n s e r t e d i n t o t h e r e p l a c e d h e p a t i c a r t e r y . T h e r e f o r e
ヲi nt h e c o m b i n a t i o n of TACE and HAIC u s i n g t h e d e v e l o p e d p o r t , two p o r t ‑ c a t h e t e r s y s t e m s must be p l a c e d i n b o t h h e p a t i c a r t e r i e s .
T h e r e a r e s e v e r a l l i m i t a t i o n s i n t h i s s t u d y . F i r s t l y , t h e i n v i v o s t u d y w
出p e r f o r m e d u s i n g o n l y one p i g . S e c o n d l y , we u s e d a n o r m a l punc 加 r en e e d l e . B e f o r e c l i n i c a l u s e of t h i s s y s t e m, development of a Huber n e e d l e w i t h an o u t e r c y l i n d e r i s e s s e n t i a l . T h i r d l y , t h e t o l e r a b i l i t y of t h e s i l i c o n septum by m u l t i p l e p u n c t
町 田u s i n g a 20
・gaugen e e d l e must be c h e c k e d .
I n c o n c l u s i o n , a m i c r o c a t h e t e r a c c e s s p o r t
W出d e v e l o p e dand t h e f e
部i b i l i t yof r e p e a t e d m i c r o c a t h e t e r i n s e r t i o n was shown i n an i n v i t r o and i n v i v o s t u d y . The c o m b i n a t i o n of r e p e a t e d TACE and HAIC f o r l i v e r t u m o r s c o u l d be p o s s i b l e u s i n g t h i s d e v i c e .
C o n f l i c t of I n t e r e s t S t a t e m e n t
A l l a u t h o r s have no c o n f l i c t s of i n t e r e s t and f i n a n c i a l d i s c l o s u r e s t o d e c l a r e .
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A l l a p p l i c a b l e i n s t i t u t i o n a l and n a t i o n a l g u i d e l i n e s f o r t h e c a r e and u s e of a n i m a l s w e r e f o l l o w e d .
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加mi s 15mm. The s l o p e o f t h e f u n n e l i s 6 0 ° a n g l e . The h e i g h t o f t h e p o r t i s 18mm .
Fig2
F i r s t p a r t of t h e i n v i t r o s t u d y
A t o t a l o f 7 p u n c t u r e s i t e s were s e l e c t e d on t h e s e p t u m , c e n t e r , a n d 2mm and 4mm
c o n c e n t r i c a l l y from t h e c e n t e r . The s e p t u m was p u n c t u r e d v e r t i c a l l y by a 20
・g a u g e i n d w e l l i n g n e e d l e a n d a m i c r o c a t h e t e r was i n s e r t e d t h r o u g h t h e n e e d l e .
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The s e c o n d p
釘t of t h e i n v i t r o s t u d y u s i n g a v a s c u l a r model
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出i n s e r t e d i n t o t h e g a s t r o d u o d e n a l a r t e r y ( a r r o w ) and t h e s i d e h o l e was p o s i t i o n e d a t t h e common h e p a t i c a r t e r y ( a r r o w h e a d ) . A m i c r o c a t h e t e r w i t h a g u i d e w i r e w
出i n s e r t e di n t o t h e h e p a t i c a r t e r y t h r o u g h t h e i n d w e l l i n g p o r t
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・F ri n d w e l l i n g c a t h e t e r was p l a c e d i n t h e v a s c u l a r m o d e l . The c a t h e t e r t i p was i n s e r t e d i n t o t h e g a s t r o d u o d e n a l a r t e r y ( a r r o w ) and t h e s i d e h o l e w
出p o s i t i o n e da t t h e common h e p a t i c a r t e r y ( a η o w h e a d ) .
F i g 5
S e l e c t i v e a r t e r i o g r a p h y and CT a f t e r i n i e c t i o n o f l i p i o d o l e m u l s i o n
A m i c r o c a t h e t e r was i n s e r t e d i n t o t h e l e f t h e p a t i c a r t e r y on da y 7 ( t o p ) , t h e r i g h t a n t e r i o r h e p a t i c
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m e t a s t a s e s . R a d i o l o g y . 2 0 1 3 ; 2 6 6 ( 2 ) : 4 0 7
・3 0 .
( 2 ) Wang DS, Louie JD , Sze DY. I n t r a ‑ a r t e r i a l t h e r a p i e s f o r m e t a s t a t i c c o l o r e c t a l c a n c e r . Semin I n t e r v e n t R a d i o l . 2013 M a r ; 3 0 ( 1 ) : 1 2 ‑ 2 0 .
( 3 ) Young S , DSouza D , F l a n a g a n S , G o l z a r i a n J . Revie w o f t h e C l i n i c a l E v i d e n c e f o r t h e Use of DEBIRI i n t h e T r e a t m e n t of C o l o r e c t a l M e t a s t a t i c D i s e a s e . C a r d i o v a s c I n t e r v e n t R a d i o l . 2 0 1 7 ; 4 0 ( 4 ) : 4 9 6 ‑ 5 0 1 .
( 4 ) R i c h a r d s o n AJ , Laurence 且 i f , L a m V W . T r a n s a r t e r i a l c hemoemboliz a t i o n w i t h i r i n o t e c a n b e a d s i n t h e t r e a t m e n t of c o l o r e c t a l l i v e r m e t a s t
出 回 :s y s t e m a t i cr e v i e w . J V a s c I n t e r v R a d i o l . 2 0 1 3 ; 2 4 ( 8 ) : 1 2 0 9 ‑ 1 7 .
( 5 ) A r a i Y , Ohtsu A, S a t o Y, e t a l . Ph a s e V I I s t u d y o f r a d i o l o g i c h e p a t i c a r t e r i a l i 由 s i o nof f l u o r o u r a c i l p l u s s y s t e m i c i r i n o t e c a n f o r u n r e s e c t a b l e h e p a t i c m e t a s t a s e s
from c o l o r e c t a l c a n c e r : J a p a n C l i n i c a l Oncology Group T r i a l 0208
・D I .J V a s c I n t e r v R a d i o l . 2 0 1 2 ; 2 3 ( 1 0 ) : 1 2 6 1
・7 .
( 6 ) N i s h i o f u k u H , Tanaka T , Aramaki T , e t a l . H e p a t i c a r t e r i a l i n f u s i o n of 5
・f l u o r o u r a c i lf o r p a t i e n t s w i t h l i v e r m e t a s t a s e s from c o l o r e c t a l c a n c e r r e 企 a c t o r yt o s t a n d a r d s y s t e mic ch e moth e r a p y : a m u l t i c e n t e r , r e t r o s p e c t i v e a n a l y s i s . C l i n C o l o r e c t a l Can ce r . 2010 ; 9 : 3 0 5
・1 0 .
( 7 ) C h a p e l l e N , Maty s i ak ‑Budnik T , Dou a n e F , M e t a i r i e S , Rou g i e r P , Touch e f e u Y.
H e p a t i c a r t e r i a l i n f u s i o n i n t h e m a n a g e m e n t o f c o l o r e c t a l c a nc e r l i v e r m e t a s t a s i s : Curr e n t and f u t u r e p e r s p e c t i v e s . Dig L i v e r Di s . 2 0 1 8 ; 5 0 ( 3 ) : 2 2 0
・2 2 5 .
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( 8 ) L e n c i o n i R , A l i b e r t i C , d e B a e r e T , e t a l . T r a n s a r t e r i a l t r e a t m e n t o f c o l o r e c t a l c a n c e r l i v e r m e t a s t a s e s w i t h i r i n o t e c
組 問l o a d e dd r u g ‑ e l u t i n g b e a d s : t e c h n i c a l recommenda t i o n s . J Vasc I n t e r v R a d i o l . 2014 ; 2 5 ( 3 ) : 3 6 5
・9 .
( 9 ) Akinwande OK, P h i l i p s P , D u r a s P , P l u n t k e S , S c o g g i n s C , M a r t i n RC. S m a l l v e r s u s l 叫 e ‑ s i z e d d r u g ‑ e l u t i n g b e a d s (DEBIRI) f o r t h e t r e a t m e n t o f h e p a t i c c o l o r e c t a l meta s t a s e s : a p r o p e n s i t y s c o r e m a t c h i n g a n a l y s i s . C a r d i o v a s c I n t e r v e n t R a d i o l . 2015 ; 3 8 ( 2 ) : 3 6 1
・7 1 .
( 1 0 ) Mauri G , Varano GM, D e l l a Vigna P , e t a l . T r a n s a r t e r i a l E m b o l i z a t i o n w i t h S m a l l ‑ S i z e P a r t i c l e s Loaded w i t h I r i n o t e c a n f o r t h e T r e a t m e n t o f C o l o r e c t a l L i v e r Me t a s t a s e s : R e s u l t s o f t h e MIRACLE I I I S t u d y . C a r d i o v a s c I n t e r v e n t R a d i o l . 2018 Jun 2 7 . d o i :
1 0 . 1 0 0 7 / s 0 0 2 7 0
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回x .
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︑ P o u r s a i d A, J e n s e n MM, Huo E , G h a n d e h a r i H . P o l y m e r i c m a t e r i a l s f o r e m b o l i c and chemoembolic a p p l i c a t i o n s . J C o n t r o l R e l e a s e . 2016 ; 2 8 ( 2 40 ) : 4 1 4 ‑ 4 3 3 .
( 1 2 ) Tanaka T , N i s h i o f u k u H, Maeda S , e t a l . R e p e a t e d b l a n d ‑ TAE u s i n g s m a l l m i c r o s p h e r e s i 吋 e c t e dv i a an i m p l a n t a b l e p o r t ‑ c a t h e t e r s y s t e m f o r l i v e r m e t a s t a s e s : an i n i t i a l e x p e r i e n c e . C a r d i o va s c I n t e r v e n t R a d i o l . 2 0 1 4 ; 3 7 : 4 9 3 ‑ 7 .
( 1 3 ) N i s h i o 負 i k uH, Tanaka T , Matsuoka M, e t a l . T r a n s c a t h e t e r a r t e r i a l c h e m o e m b o l i z a t i o n u s i n g c i s p l a t i n po w d e r mixed w i t h d e g r a d a b l e s t a r c h mi c r o s p h e r e s f o r c o l o r e c t a l l i v e r meta s t a s e s a f t e r F OL F O X f a i l u r e : r e s u l t s o f a p h a s e I / I I s t udy . J V a s c I n t e r v R a d i o l . 2 0 1 3 ; 24 : 5 6 ‑ 6 5 .
( 1 4 ) Tanaka T , N i s h i o f u k u H , Hukuoka Y , e t a l . P h a r m a c o k i n e t i c s and a n t i tum o r e f f i c a c y of chemoemboliz a t i o n u s i n g 40 μm i r i n o t e c a n 初
m o d e l . J V a s c I n t e r v R a d i o l . 2014 ; 2 5 ( 7 ) : 1 0 3 7 ‑ 4 4 .
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( 1 5 ) S a t o T , Tanaka T , N i s h i o f u k u H, e t a l . P h a r m a c o k i n e t i c s and H i s t o p a t h o l o g i c a l F i n d i n g s of Chemoembolization Using C i s p l a t i n Powder Mixed w i t h D e g r a d a b l e S t a r c h M i c r o s p h e r e s i n a R a b b i t L i v e r Tumor Model. C a r d i o v a s c I n t e r v e n t R a d i o l 2 0 1 7 ; 4 0 ( 3 ) : 4 3 8
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and C a p e c i t a b i n e i n R e f r a c t o r y L i v e r P r e v a l e n t C o l o r e c t a l M e t a s t a s e s : A Phase I I S i n g l e ‑ C e n t e r S t u d y . C a r d i o v a s c I n t e r v e n t R a d i o l 2 0 1 5 ; 3 8 ( 6 ) : 1 5 2 3 ‑ 3 1 .
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( 1 9 ) A r a i Y, Takeuchi Y, I n a b a Y, e t a l . P e r c u t a n e o u s c a t h e t e r p l a c e m e n t f o r h e p a t i c a r t e r i a l i n 白 s i o nc h e m o t h e r a p y . Tech Vasc I n t e r v e n t i o n a l Rad 2 0 0 7 ; 1 0 : 3 0
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454 6 f i x a t i o n f o r h e p a t i c a r t e r i a l i n f u s i o n c h e m o t h e r a p y . J Vasc I n t e r v R a d i o l 2 00 3 ; 1 4 : 6 3 ‑ 8 .
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