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Al tera tions in Co lo n ic M uc os a l Vesselsin Patients With Cirrhosis a n d N on cirrh oticPortal HypertensionL A U R A W. L A M P S , M D , C H R I S T IN E M . H U N T , M D , A N N E T T E G R E E N ,M P H , G E O R G E F. G R A Y , JR , M D , A N D K AY W A S H I N G T O N , M D , P HD

C h a n g e s i n in t e s t in a l m n c o s a l m i c r o v a s c u l a t u r e a s a c a u s e o fl o w e r g a s t r o i n t e st i n a l h e m o r r h a g e i n p a t i e n ts w i t h p o r t a l h y p e r t e n -s i o n h a v e b e e n w e l l d o c u m e n t e d c l in i c al ly , b u t t h e a n a l o g o u s h i s t o m o r -p h o l o g i c a l c h a n g e s h a v e n o t b e e n w e l l c h a r a c te r i z e d . T h e g o a l o f t h iss t u d y w a s t o e v a l u a t e q u a l i ta t i v e a n d q u a n t i t a t i v e c h a n g e s i n c o l o n i cm u c o s a l v e s s e l s i n p a t i e n t s w i t h c i r r h o s i s o r c l i n i c a ll y e v i d e n t p o r t a lh y p e r t e n s i o n a n d t o c o r r e l a te t h e s e c h a n g e s w i t h e n d o s c o p i c a n dc l in i c a l f i n d i n g s . C o l o n b i o p s y o r r e s e c t i o n s p e c i m e n s l id e s f r o m 4 6p a t i e n t s w i t h b i o p s y - p r o v e n c i r r h o s is ( 4 4 p a t i e n ts ) o r n o n c i r r h o t i cp o r t a l h y p e r t e n s i o n ( t w o p a t ie n t s ) w e r e re v i e w e d . I m m u n o p e r o x i -d a s e s t a i n f o r C D 3 4 a n t i g e n w a s u s e d t o f a c i li t a t e v i su a l i z a t io n o fm u c o s a l v e s s e l s, a n d v e s s e l d i a m e t e r w a s m e a s u r e d w i t h a m i c r o m e -t er . P a t i e n t s w i t h i n f la m m a t o r y b o w e l d i s e a s e w e r e e x c l u d e d . T w e n t y -f o u r n o r m a l c o l o n b i o p s y s p e c i m e n s s e r v e d a s c o n t r o l s. M u c o s a lv e s s e l s w e r e d i v i d e d i n t o s u p e r f i ci a l , i n t e r m e d i a t e , a n d d e e p l a y e r s .A s a g r o u p , t h e c i r r h o t i c p a t i e n t s h a d a s i g n i f i c a n t l y h i g h e r m e a n

d i a m e t e r o f v e s s e l s i n a l l t h r e e l a y e r s . Q u a l i t a t i v e ly , i n c r e a s e d n u m -b e r s o f s m a l l v e ss e l s a n d p r o m i n e n t b r a n c h i n g w e r e n o t e d , e s p e c i a l l yi n t h e s u p e r f i c i a l a n d i n t e r m e d i a t e l a y e r s . T o r t u o u s , t h i c k - w a l l e dv e s s e l s, s u g g e s t i n g a r t e r i a li z a t io n o f v e n u l e s , w e r e p r e s e n t i n s o m ec a s e s . E l e v e n p a t i e n t s h a d e n d o s c o p i c f i n d i n g s s u g g e st i v e o f v a s c u la ra b n o r m a l i t i e s, i n c l u d i n g e r y t h e m a t o u s m u c o s a l p a t c h e s , r e d m a c u l e s ,a n d t e l a n g i e ct a s i a s. E i g h t e e n h a d e s o p h a g e a l v a r i c e s , a n d f i v e h a dp o r t a l g a s t r o pa t h y . N i n e t e e n p a t i e n t s h a d g a s t r o i n t es t i n a l ( G I ) b l e e d -i n g , l o c a l i z e d t o t h e l o w e r G I t r a ct i n 1 1 . T h e s e q u a l i ta t i v e a n dq u a n t i ta t i v e f i n d i n g s s u g g e s t t h a t c o l o n i c m u c o s a l v a s c u l a r l e si o n s a r ec o m m o n i n p o r t a l h y p e r t e n s i o n a n d m a y r e p r e se n t a p o t e n t i a l s o u r c eo f c l in i c a ll y si g n i f ic a n t l o w e r G I h e m o r r h a g e i n t h e s e p a t i e n t s . H U MP A x n o L 2 8 :5 2 7 - 5 3 5 . C o p y r i g h t 1 9 9 8 b y W . B . S a u n d e r s C o m p a n y

Key words: p o r t a l c o l o p a t h y , p o r t a l h y p e r t e n s i o n , c i r r h o si s , c o l o n ,v a s c u l a r e c t a s i a s .

Abbrev iat ions: G I , g a s t ro i n t e st i n a l; H & E , h e m a t o x y l i n - e o s i n .

A l t h o u g h h e m o r r h o i d s a n d r e c t a l v a r i c es a re r e -p o r t e d t o b e t h e m o s t c o m m o n c a u s e s o f l o w e r g a s t r o in -t e s t in a l ( G I ) b l e e d i n g i n p a t i e n t s w i th p o r t a l h y p e r t e n -s i o n , ~,2 t h e r e h a s r e c e n t l y b e e n i n c r e a s e d i n t e r e s t i nc h a n g e s o f t h e i n t e s ti n a l m u c o s a l m i c r o v a s c u l a t u r e a s ac a u s e o f b o t h a c u t e a n d c h r o n i c l o w e r G I t r a c t h e m o r -r h a g e in t h i s p o p u l a t i o n Y T h e m o r p h o l o g i c a l f e a t u re so f p o r t a l g a s t r o p a t h y a r e w e l l d e fi n ed 7 -1 ; h o w e v e r ,a n a l o g o u s c h a n g e s o f t h e m u c o s a l v e s s el s w i t h i n t h es m a l l b o w e l a n d c o l o n h a v e n o t b e e n e x t e n s i v e ly s t u d -i e d o r c h a r a c t e r i z e d .

E n d o s c o p i c a l l y , c o l o n i c m u c o s a l c h a n g e s i n p a -t i e n ts w i t h p o r t a l h y p e r t e n s i o n h a v e i n c l u d e d t e l a n g i e c -t as ia s o r a n g i o d y s p l a s i a - l i k e l e s io n s , e r y t h e m a t o u sp a t c h e s , a n d v a r i c es ; 2,4,n t h e s e l e s i o n s h a v e b e e n r e -p o r t e d t h r o u g h o u t t h e e n t i r e c o l o n . 6 T h e c l in i c a l s ig n i fi -c a n c e o f t h e s e v a s c u l a r l e s io n s , t h e i r r e l a t i o n s h i p t o t h es e v e r i t y o f t h e u n d e r l y i n g l i v e r d i s e a s e , t h e r i s k o fb l e e d i n g a s s o c i a t e d w i t h th e m , a n d t h e i r a s s o c i a t i o nw i t h p o r t a l g a s t r o p a t h y a r e n o t w e l l e s t a b l i sh e d .

I n t h i s st u d y , w e e v a l u a t e d t h e q u a l i t a t i v e a n dq u a n t i t a t i v e c h a n g e s i n c o l o n i c m u c o s a l v e ss e ls in 4 6p a t i e n t s w i t h c i r r h o s is o r c l i n ic a l ly e v i d e n t p o r t a l h y p e r -t e n s io n a n d c o r r e l a t e d t h e m w i th e n d o s c o p i c a n dc l i n i c a l f i n d i n g s .

From the D epa rtm ent o f Pathology, Varlderbil t Universi ty Medi-cal Center , Nashvil le , TN; the D epa rtme nt of Medicine, Duke Univer-s i ty Medica l Cen te r , Durham, NC; and Independen t Consu l tan t inBiostat is t ics , Durham, NC. Accepted for publicat ion September 3,1997.Address cor responden ce an d repr in t r eques t s to Kay Wash ing-ton, MD, PhD, Department of Pathology, Vanderbil t Universi tyMed ical Center , Nashville , TN 37232.Copy right 1998 by W .B. Saunders Company0046-8177/98/2805-001658.00/0

M AT ERIAL S AN D M ET HODSP a t i e n t s w i t h h i s t o l o g i c a l l y p r o v e n c i r r h o s i s o r n o n c i r -

r h o t i c p o r t a l h y p e r t e n s i o n w e r e i d e n t i f i e d b y s e a r c h in g t h es u r g i c a l p a t h o l o g y f il e s o f D u k e U n i v e r s i t y M e d i c a l C e n t e ra n d V a n d e r b i l t U n i v e r s i t y M e d i c a l C e n t e r . A s u b s e t o f 4 6 o ft h e s e p a t i e n t s ( 4 4 p a t i e n t s w i t h c i r r h o s i s , t w o w i t h n o n c i r -r h o t i c p o r t a l h y p e r t e n s i o n ) h a d c o l o n b i o p s i e s ( 5 9 s p e c i -m e n s ) o r r e s e c t i o n s ( s i x s p e c i m e n s : t w o , r ig h t c o l o n ; o n e ,t r a n s v e r s e c o lo n ; t w o , e n t i r e c o l o n ; o n e , s i g m o i d c o l o n )a v a i l a b l e f o r r e v ie w . M e d i c a l r e c o r d s f o r e a c h p a t i e n t w e r er e v i e w e d t o c o n f i r m t h a t t h e p a t i e n t w a s c i r r h o t i c a t t h e t i m et h e c o l o n b i o p s y o r r e s e c t i o n s p e c i m e n w a s o b t a in e d , f o r s ig n sa n d s y m p t o m s o f p o r t a l h y p e r t e n s i o n , a n d f o r e s t i m a t e dd u r a t i o n o f c i rr h o si s . T h e f o l lo w i n g w e re c o n s i d e r e d i n d i ca -t iv e o f p o r t a l h y p e r t e n s i o n : s p l e n o m e g a l y , e s o p h a g e a l v a r ic e s ,p o r t a l g a s t ro p a t h y , a n d e v i d e n c e o f h y p e r s p l e n i s m s u c h a st h r o m b o c y t o p e n i a . O t h e r i n f o r m a t i o n r e c o r d e d i n c l u d e d t h ec a u s e o f c i rr h o s i s , i n d i c a t i o n f o r c o l o n o s c o p y o r r e s e c t i o n ,a n d f i n d in g s a t e n d o s c o p y o r s u r g er y . T h e p r e s e n c e o f r e ct a lv a r i c e s o r h e m o r r h o i d s w a s n o t e d , a s w e l l a s d e s c r i p t i o n s o ft h e c o l o n i c m u c o s a s u g g e s t iv e o f v a s c u l a r l e si o n s s u c h a s r e dm a c u l e s o r t e l a n g i e c t a t i c le s i o n s . P a t i e n t s w i th i n f l a m m a t o r yb o w e l d i s ea s e o r p r i o r a b d o m i n a l s u r g e r y w e r e e x c l u d e d f r o mt h e s t u dy . R e s e c t i o n s p e c i m e n s f r o m p a t i e n t s w i t h a d e n o c a r c i -n o m a o f t h e c o l o n w e r e a ls o e x c l u d e d .A g r o u p o f 2 4 c o n t r o l c o l o n b i o p s y sp e c i m e n s w a s c h o s e nr a n d o m l y fr o m r e c e n t c a s es w i t h n o d i a g n o s t i c a b n o r m a l i t y .M e d i c a l r e c o r d s w e r e re v i e w e d t o d e t e r m i n e t h a t n o n e o ft h e s e 1 6 p a t i e n t s h a d k n o w n l i v e r d i s e a s e o r i n f l a m m a t o r yb o w e l di s ea s e , a n d t h a t n o n e h a d u n d e r g o n e p r e v i ou s a b d o m i -n a l s u r g e r y .A l l c o l o n b i o p s i e s o r r e s e c t i o n s p e c i m e n s w e r e f i x e d i nb u f f e r e d f o r m a l i n a n d p r o c e s s e d r o u t i n e l y . A t le a s t t w oh e m a t o x y l i n a n d e o s i n ( H 8 c E ) - s t a i n e d l e ve l s w e r e a v a i l a b l ef o r r e v ie w fo r e a c h b i op s y. A n i m m u n o p e r o x i d a s e s t ai n f o rC D 3 4 ( H P C A - 1 , B e c t o n D i c k i n s o n , S a n J o s e , C A ; 1 : 1 0 d il u -

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" i , ' $ U P E R F I I 2 1 A L , :

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,. . I N T E R N I E D ! A T E

. 51 I 1 E E P

FIGURE 1 . Schematic rep-resentation of normal co-ionic mucosal vasculature.

tion) was performed to facilitate visualization of mucosalvessels in all cases with available blocks.Vessel diameter was measured on the CD34-stained slidesat 400 magnification with a calibrated ocular micrometer.For one case, no block was available, and vessels weremeasured on the H&E-stained slide. The area of greatestvascular dilatation was chosen, and all identifiable vessels weremeasured in 5 to 10 high-power fields. The mean vesseldiameter was calculated for superficial, in termediate, anddeep mucosal vessels. The Wilcoxon test for unpa ired data, anonparametric test based on a ranking system and reputed tohave a high degree of efficiency, was used to determinewhether there were a significant difference in mean vesseldilatation between cases and controls.

RESULTSNormal Mucosa

The vessels in normal colonic mucosa from controlcases were classified into three layers: superficial, inter-mediate, and deep vessels (Fig 1). Superficial vesselswere def ined as the chainlike layer of small capillaries,lying just ben eat h the su rface epithelial cells. This layerwas inconspicuous on H&E-stained sections of normalcolon and was better visualized on CD34-stained sec-tions. I nter medi ate vessels were d efin ed as the vessels inthe midportion of the lamina propria. In normalmucosa, these vessels rarely had identifiable branchesand were often vertically oriented. Deep vessels weredefi ned as the layer of vessels immediate ly adjace nt tothe muscular is mucosae ; these were usually seen in crosssection in well-oriented specimens. No site-specific dif-ferences in vascular diameter were shown in the co ntrolbiopsy specimens, which consisted of 14 specimensfrom the left colon or rectum, five from the cecum orright colon, an d five ra ndo m biopsy specimens.Cirrhosis

Vessels in colon biopsy specimens and resectionspecimens from cirrhotic patients had significantlyhigher mean diameters in all three vessel layers thanmucosal vessels in the control group (Table 1), al-

though there was overlap between the groups as illus-trated by the frequency histograms for each layer ofvessels (Figs 2-4). For the superf icial lay er of vessels, themean vessel diameter in 17 of 65 biopsy specimens orresections fell outside the r ang e of the cont rol cases.For the inte rmed iate layer of vessels, the mea n vesseldiameter in 31 cases fell outside the range of controlcases. For the dee p layer of vessels, the mea n vesseldiame ter in 33 cases fell outside o f the ran ge o f thecontr ol cases (Fig 5). Subtle de grees of vascular dilata-tion (defined as vascular luminal diame ter g reater tha nthe upper range of the control cases) were difficult torecognize on H&E-stained slides and were m ore readilyapprecia ted on the CD34-stained sections. Many of thebiopsies contained dilated vessels in more than onelayer. Fou rte en patients had dilated vessels in two layersonly; seven had dilated vessels in all three layers. A totalof 34 of 46 patients (73.9%) with cirrhosis or noncir-rhotic portal hypertension had dilated vessels in at least

T ABL E | , Mean Diame ter of Colonic Mucosal Vesselsin Patients With Cirrhosis or Noncirrhotic PortalHypertension and ControlsCirrhosis/PortalHypertension Controls

(N = 65 spec imens , (N = 24 spec imens,46 patients) 16 patients)Superficial vesselsMean dia met er (tam) 7.84 5.27Range 4.03-22.68 3.354.50Standard deviat ion 3.15 1.11P


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L~F IG U R E2. F requenc y h is to -g r a m s h o w i n g r a n g e o f d i -a m e t e r s o f s u p e r f i c i a l c o - , 1 : 1I on i c m u c os a l v es s els i n En o r m a l a n d c i rr h o t ic p a - =t ients, z

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12 13 >14R a n g e , V e s s e l D i a m e t e r i n M i c r o n s

o n e l a ye r . T w e l v e c i r rh o t i c p a t i e n t s h a d n o d i l a t e dv e s se l s i n a n y o f t h e t h r e e l a y e rs .Q u a l i t a t i v e c h a n g e s i n m u c o s a l v e ss e ls w e r e n o t e di n a d d i t i o n t o q u a n t i t a t i v e c h a n g e s i n v a s c u l a r d i a m e t e r .

T h i n - w a l l e d s u p e r f i c i a l v es s el s w e r e d i f f u s e ly d i l a t e d a n dt o r t u o u s a n d o f t e n c o n g e s t e d i n b io p s y s p e c i m e n s f r o ms o m e c i r r h o t i c p a t ie n t s . T h i c k e n e d v a s c u la r w al ls w e r en o t s e e n i n t h i s s u p e r f i c i a l l a y e r . I n o t h e r p a t i e n t s , t h e

8

7

6(3"6

3

i5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

FIG U R E3. F requenc y h is to -g r a m s h o w i n g r a n g e o f d i -ameters o f intermediate c o -lon i c m uc os a l v es s e ls i nn o r m a l a n d c i r r h o t i c p a -t ients.

>20Range, Vesse l D i am eter i n m i crons

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HUMAN PATHOLOGY Vol ume 29, No. 5 (M ay 1998)6

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[-1 Cirrh otics!11Con t ro s

,IRange, Vessel Diameter in microns

FIGURE4. Frequencyhisto-gram showing range of di-ameters o f deep mucosa lcolonic vessels in normaland cirrhotic patients.

i nc r e a se i n va sc u l a r d i a m e t e r i n t he supe r f i ci a l l a yer wa sf oc a l a nd m o r e r e a d i ly v i sib le on t h e C D - 34 - s t a ine dsec t ion than on H&E s ta in (F ig 6) . In genera l , vascula rd i la ta t ion involv ing th is laye r was mor e d i f f icu l t toiden t i fy tha n in o th e r laye rs. S imi la rly , in some c i r rho t icpa t i e n t s, t he i n t e r m e d ia t e ve ssel s w e r e m o r e t o r tuous( F ig 7 ) , a nd t he b r a nc he s w e r e m or e r e a d i ly s e e n t ha ni n n o r m a l m u c o s a . I n r e s e c t i o n s p e c i m e n s a n d s o m eb i o p s y s p e c i m e n s w i th a b u n d a n t s u b m u c o s a , d i l a t e dsubm uc osa l ve sse ls t ha t na r r ow e d a s the y t r a ve r se d t hem usc u la r i s m uc osa e w e r e s e e n ; i n m os t c a se s , t he seve ssel s ha d t h in w a ll s, bu t i n o th e r s a t h i c ke ne d m usc u -la r laye r was pre sen t (F ig 8) . A granu la t io n t i ssue - l ikep r o l i f e r a t i on o f de nse ly pa c ke d sm a l l ve s se l s , w i thou t

a s soc i a t e d i n f l a m m a t ion , w a s p r om ine n t i n spe c im e nsf r om f ive pa t i e n t s ( F ig 9 ) . A n inc r e a se d de ns i t y o f sm al lve ssel s i n t he l a m ina p r op r i a w a s f oca l l y p r e se n t i n a na dd i t i ona l 26 spe c im e ns f r o m 17 pa t i e n t s . I n a ll bu t oneof these spec im ens , d i la t ion of mucosa l vesse ls wasp r e se n t i n o the r a r e a s . C o lon i c c r yp t s i n p r om ine n ta reas of inc reased vascula r dens i ty were los t or d is -t o r t e d , bu t d i f f u se m uc osa l a r c h i t e c tu r a l c ha nge s o fchr oni c co l i t is were n ot se en in an y case (F ig 10) .O t h e r m u c o s a l c h a n g e s i n c l u d e d s l i g h t m u c o s a le de m a ( th r e e c a se s) , re a c t ive c ha nge s i n c r yp t e p i t he -l i um ( th r e e c a ses ) , f oc a l i n f i l t r a t i on o f t he l a m inap r op r i a by ne u t r o ph i l s ( t h r e e c a se s) , a nd f oc a l m uc osa la r c h i t e c tu r a l d i s to r t i on ( 13 c a se s ) c ons i s t ing o f d r o po u t

FIGURE 5. Dilated vessels in the intermedia te and d eep layersof the colonic mucosa. (Hematoxylin and eosin, orig inal magni-f ication x400).

FIGURE 6. CD 34 staining highlights a di lated, branchedvessel in the superficia l layer. (Indirect immunoper oxidase stain-ing for CD34, orig inal magnif icati on 400.)

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COLO NIC MUC OSAL VESSELS N CIRRHOSIS (Lamps et al)

FIGURE 7. Marke dly tortuous vessel in interm ediate layer ofmucosa. (Hematoxyl in and eosin, original magnif icat ion x400,)

of occasional crypts and minor degrees of distortion incrypt orientation (Fig 10). Branching crypts were notpresent. The mononu clear inf lammatory cell infiltratein the l amina propria was in general sparse, although itwas slightly increased in five specimens from patientswith dilated vessels. No increase in chronic inflamma-tory cells was seen in any of the biopsy specimenswithout dilated vessels from patients with cirrhosis ornoncirrhotic portal hypertension. On endoscopic exami-

FIGURE 8. Dilated de ep vessel wh ich traverses the muscularismucos ae. (He matoxylin and eosin, original mag nification 400.)

FIGURE 9. Gra nulat ion tissue-like proliferation of dens elypac ked small vessels withou t associated inf lammation, (Hema-toxylin and eosin, original ma gnific ation 200),

FIGURE 10. Architectural changes including crypt dro poutand mild distort ion can mimic quiescent inf lammatory boweldisease, (Hematoxy lin and eosin, original ma gnific ation x l00.)

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HUMAN PATHOLOGY Vo lum e29, No. 5 (May 1998)n a t i o n , f o u r p a t i e n t s , a l l w i t h d i l a t e d m u c o s a l v e s s e l s ,h a d m u c o s a l f r ia b i li t y o r o t h e r c h a n g e s s u g g e st iv e o fc o l it is . B i o p s y s p e c i m e n s i n t w o o f t h e s e c a s es s h o w e df o c a l c r y p t d i s t o r t i o n ; t h e m n c o s a i n t h e o t h e r t w ob i o p s y s p e c i m e n s w a s e d e m a t o u s , a n d i n o n e b i o p s ys p e c i m e n , r a r e s m a l l c o ll e c t io n s o f n e u t r o p h i l s w e r ep r e s e n t i n t h e l a m i n a p r o p r i a .

C i r r h o t i c p a t i e n t s w i t h d i l a t e d c o l o n i c m u c o s a lv e s se l s w e r e m o r e l i k e ly t o h a v e p o r t a l g a s t r o p a t h y ,h e m o r r h o i d s , a n d l o w e r g a s t ro i n te s t in a l h e m o r r h a g et h a n t h o s e w i t h v e ss el s o f n o r m a l d i a m e t e r ( T a b le 2 ) ,a l t h o u g h t h e s e a s s o c i a t i o n s w e r e n o t s t a ti s ti c a ll y s i gn i f i-c a n t w h e n c o m p a r e d u s i n g F is h e r ' s e x a c t te s t. T h e yw e r e l e ss l ik e l y t o h a v e h a d e p i s o d e s o f u p p e r G Ih e m o r r h a g e , a l t h o u g h t h e p r e v a l e n c e o f e s o p h a g e a lv a r ic e s w a s r o u g h l y t h e s a m e a s i n t h e c i r r h o t i c p a t i e n t sw h o d i d n o t h a v e d i l a t e d c o l o n i c m u c o s a l v e s s e l s . T h es p e c i f i c l o c a t i o n o f t h e d i l a t e d v e s s e l s ( s u p e r f i c i a l ,i n t e r m e d i a t e , o r d e e p l a y e r ) w a s n o t s i g n i f i c a n t l y a s so c i-a t e d w i t h g a s t r o i n t e s ti n a l h e m o r r h a g e . D i l a t e d i n t e r m e -d i a t e v e ss e ls w e r e m o r e l i k e ly t o o c c u r i n t h e l e f t c o l o n ,b u t f o r m a n y c a s e s r a n d o m b i o p s y s p e c i m e n s w e r et a k e n , o r t h e p r e c i s e b i o p s y s i t e w a s n o t s p e c i f i e d ,m a k i n g c o r r e l a t i o n o f v a s cu l a r c h a n g e s w i t h s i te d i ff i-cu l t . E n d o s c o p i c f i n d i n g s s u g g e s ti v e o f v a s c u l a r l es i o n si n c i r r h o t i c p a t i e n t s w i t h d i l a t e d v e s s e l s o n h i s t o l o g i ce x a m i n a t i o n i n c l u d e d p a t c h y e r y t h e m a , p u n c t a t e r e dm a c u l e s , t e l a n g i e c t a s i a , a n d , i n o n e p a t i e n t , v i s u a l i z a -t i o n o f a b l e e d i n g v e ss e l i n t h e c e c u m ( T a b l e 3 ) . B i o p s ys p e c im e n s o f m u c o s a t h a t a p p e a r e d n o r m a l t o th ee n d o s c o p i s t r a r e l y s h o w e d m u c o s a l v a s c u l a r c h a n g e s .B i o p s y s p e c i m e n s o f m u c o s a l e r y t h e m a s u g g e s ti v e o fc o l i t i s o r l e s i o n s c h a r a c t e r i z e d a s " v a s c u l a r " o n e n d o s -c o p y s h o w e d v as c u l ar a b n o r m a l i t i e s i n m o r e t h a n h a l ft h e c a se s ( T a b le 3 ) . E r y t h e m a o r e n d o s c o p i c f i n d i n g ss u g g e s t i v e o f v a s c u l a r c h a n g e s w e r e s e e n i n 3 o f 1 2c i r r h o t i c p a t i e n t s w i t h o u t d i l a t e d v e s s e l s o n h i s t o l o g i ce x a m i n a t i o n . O n e o f th e s e p a t i e n t s h a d f i n d i n g s su g g e s-t iv e o f c e c al a n g i o d y s p l as i a ; n o b i o p s y o f t h e c e c u m w a so b t a i n e d , a n d t h e s i g m o id , w h i c h u n d e r w e n t b i o p s ya n d w a s h is t o lo g i c a ll y u n r e m a r k a b l e , w a s f r e e o f m a c r o -s c o p i c l e s i o n s s u g g e s ti v e o f v a s c u l a r a b n o r m a l i t i e s . A n -o t h e r p a t i e n t w h o u n d e r w e n t e n d o s c o p y to r u le o u t

i n f l a m m a t o r y b ow e l d i se a s e h a d r e c ta l e r y t h e m a ,t h o u g h t t o b e s e c o n d a r y t o p r e p a r a t i o n f o r e n d o s c o p y ;t h e b i o p s y s p e c i m e n i n t h i s c a s e w a s a l s o n o r m a l . At h i r d p a t i e n t w i t h c e ca l e r y t h e m a h a d f o c a l a c u t e c o l i ti so n b i o p s y , w i t h o u t d i l a t e d v e s s e l s . I n a l l s i x c a s e s w i t hr e s e c t i o n s p e c i m e n s , t h e i n d i c a t i o n f o r s u r g e r y w asa c t i v e l o w e r G I b l e e d i n g . D i l a t e d d e e p v e s s e l s w e r ei d e n t i f i e d i n a l l s i x s p e c i m e n s ; i n a d d i t i o n , t w o h a dd i l a t e d i n t e r m e d i a t e v e s s e l s , a n d t h r e e h a d d i l a t e dsupe r f i c i a l ves se l s.B i o p s y s p e c i m e n s f r o m 1 2 p a t ie n t s w i t h p o r t a lh y p e r t e n s i o n c o n t a i n e d v e s se ls o f n o r m a l d i a m e t e r i na l l t h r e e l a y e r s . T h e r e w a s n o d i f f e r e n c e i n t h e p r e v a -l e n c e o f e s o p h a g e a l o r g a s t ri c v ar ic e s i n t h i s g r o u pc o m p a r e d w i t h t h e c i r r h o t i c g r o u p w i t h d i l a t e d v e ss el s.C i r r h o t i c p a t i e n t s w i t h o u t d i l a t e d m u c o s a l v e s se ls w e r em o r e l i k e ly t o h a v e h a d p r e v i o u s e p i s o d e s o f u p p e r G Ih e m o r r h a g e b u t w e r e l es s l ik e l y t o h a v e h a d l o w e r G Ih e m o r r h a g e o r h e m o r r h o i d s . N o c as es o f p o r t a l g as tr o p -a t h y w e r e i d e n t i f i e d i n t h e c i r r h o t i c p a t ie n t s w i t h o u td i l a te d c o l o n i c v es se ls w h o h a d u n d e r g o n e u p p e r G Ie n d o s c o p y .C l i n i c a l F e a t u r e s

T h e m e a n a g e o f t h e p a t i e n t s w i t h ci r r h o si s o rn o n c i r r h o t i c p o r t a l h y p e r t e n s i o n w a s 5 3 .2 y e a r s ( r a n g e ,1 8 to 8 2 y e a r s) , c o m p a r e d w i t h a m e a n a g e o f 5 7.1 y e a r s( r a n g e , 3 6 t o 7 5) f o r t h e c o n t r o l g r o u p . I n t h e c i r r h o si sg r o u p , 1 7 o f th e p a t i e n ts w e re w o m e n a n d 2 9 w e r e m e n ,c o m p a r e d w i th 1 0 w o m e n a n d s ix m e n i n t h e c o n t r o lg r o u p . N o r e l a t i o n s h i p b e t w e e n c a u s e o f c i r rh o s i s a n dc h a n g e s i n c o l o n i c m u c o s a l v e ss el s w a s n o t e d ( T a b le 4 ) .I n d i c a t i o n s f o r c o l o n o s c o p y i n t h e c i r r h o t i c g r o u pi n c l u d e d s c r e e n i n g f o r c o l o n p o l y p s / c a r c i n o m a ( e i g h tp a t i e n t s ) , e x c l u s i o n o f i n f l a m m a t o r y b o w e l d i se a s e int h r e e p a t i e n t s w i t h p r i m a r y s c l e ro s i n g c h o l a n g i t is , e v a lu -a t i o n o f d i a r r h e a ( s ev e n p a t ie n t s ) , a n d e v a l u a t i o n o fg a s t r o i n t e s t i n a l b l e e d i n g o r a n e m i a ( 1 4 p a t i e n t s ) . T h ei n d i c a t i o n f o r s u r g e r y i n a l l s ix r e s e c t i o n c a s e s w a s l o w e rG I b l e e d i n g . T w e n t y -s ix c ir r h o t i c p a t i e n t s h a d u p p e rg a s t r o i n t e s t i n a l e n d o s c o p y , w h i c h r e v e a l e d e s o p h a g e a lv a r i c e s i n e i g h t e e n , g a s t r i c v a r i c e s i n t h r e e , a n d p o r t a lg a s t r o p a t h y i n fi ve . N i n e t e e n p a t i e n t s h a d p r i o r e p i-

T A B L E 2 . E ndos c op i c and Cl in ic a l Features of Pat ients With Cirrhosis or No nci rrho t ic Porta l H ypertens ionDilated Vessels, Dilated Superficial Dilated Intermediate Dilated Deep No DilatedAny Layer Vessels Vessels Vessels Vessels

No. of patients 34/46 (73.9%) 18/46 (39.1%) 17/46 (40.0%) 25/46 (54,3%) 12/46 (26.1%)Mean age (yr) 49.8 54.9 56.8 51.1 57.3Esophageal varices 13/17" (76.5%) 7/1;[* (63.6%) 6/8* (75.0%) 10/12" (83,0%) 5/8* (62.5%)Gastric varices 2/17" (11.8%) 1/11" (9.1%) 1/8" (12.5%) 2/12" (16,7%) 1/8" (12.5%)Portal gastropathy 5/17" (29.4%) 2/11" (18.2%) 3/8* (37.5%) 4/12" (33.3%) 0/8* (0.0%)UGI hemorrhage 4/34 (11.8%) 1 (5.6%) 2 (11.1%) 3 (11.5%) 4 (33.3%)LGI hemorrhage 10/34 (29.4%) 4 (22.2%) 4 (22.2%) 8 (30.8%) 1 (8.3%)Hemorrhoids 10/34 (29.4%) 5 (27.8%) 5 (27.8%) 8 (30.8%) 1 (8.3%)Site:Right colon 12/48 (25%) 7 (38.8%) 3 (13.6%) 10 (38.5%) 2 (16.7%)Transverse 4/48 (8.3%) 2 (11.1%) 3 (13.6%) 2 (7.7%) 2 (16.7%)Left colon 19/48 (39.6%) 6 (33.3%) 11 (50.0%) 12 (46.2%) 5 (41.7%)Unknown 13/48 (27.1%) 3 (25.0%) 5 (22.7%) 9 (34.6) 3 (25%)*Denominator represents number of patients who underwent upper gastrointestinal endoscopy.

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CO LO NIC MUC OSAL VESSELS N CIRRHOSIS (Lamps et al)TABLE 3 . C o l o n o s c o p i c F i n d in g s i n P a t i e n ts W i t h C ir rh o s is o r N o n c i r r h o t i c P o r t a l H y p e r t e n s i o n

D i l a t e d V e sse ls , Su p e r f i c i a l V e sse ls In t e rm e d i a t e V e sse ls D e e p V e sse ls N o D i l a t e dFi n d i n g s A n y La y e r D i l a t e d D i l a t e d D i l a t e d V e sse lsE n d o s c o p i c 6 / 1 9 " ( 3 1 . 6 % ) 5 / 1 0 " ( 5 0 .0 % ) 3 / 1 0 " ( 3 0 % ) 6 / 1 6 " ( 3 7 .5 % ) 3 / 6 * ( 5 0 .0 % )V a sc u l a r l e s i o n s" C o l it is " 4 / 1 9 " ( 2 1. 0% ) 3 / 1 0 " ( 3 0 % ) 3 / 1 0 " ( 3 0% ) 4 / 1 6 " ( 2 5% ) 0P r o m i n e n t f o l d o r i l e o c e c a l v al ve 2 / 1 9 " ( 1 0 . 5 % ) 1 / 1 0 " ( 1 0 % ) 1 / 1 0 " ( 1 0 % ) 1 / 1 6 " ( 6 . 3 % ) 0U l c e r 2 / 1 9 " ( 1 0 .5 % ) 1 / 1 0 " ( 1 0 % ) 2 / 1 0 " ( 1 0 % ) 0 0D i v e r t i c u la r 2 / 1 9 " ( 1 0 . 5 % ) 2 / 1 0 " ( 2 0 % ) 1 / 1 0 " ( 1 0 % ) 1 / 1 6 " ( 6 . 3 % ) 2 / 6 * ( 3 3 .3 % )N o r m a l 1 / 1 9 " ( 5 . 3 % ) 0 0 1 / 1 6 " ( 6 . 3 % ) 1 / 6 " ( 1 6 .7 % )

* D e n o m i n a t o r r e p r e s e n t s n u m b e r o f p a t i e n t s ,a dt h a v a i la b l e e n d o s c o p i c r e p o r t s .s o d e s o f G I b l e e d i n g , l o c a l i z e d t o t h e l o w e r G I t r a c t i n1 1. E l e v e n p a ti e n t s h a d h e m o r r h o i d s , s p e c i f ie d a s i n t e r-n a l in e i g h t a n d e x t e r n a l i n o n e .I n d i c a t i o n s f o r c o l o n o s c o p y i n t h e c o n t r o l g r o u p o f1 6 p a ti e n t s w e r e e v a l u a t i o n o f d i a r r h e a ( 13 p a t i e n t s ),a b d o m i n a l p a i n ( tw o p a t i e n t s ), a n d s c r e e n i n g / s u r v e i l -l a n c e f o r c o l o n p o l y p s ( o n e p a t i e n t ) .

D I SCUSS I ON

M t e r a t i o n s i n c o l o n i c m u c o s a l v a s c u l a t u r e , as v i su -a l i z e d o n e n d o s c o p i c e x a m i n a t i o n i n p a t i e n t s w i t hc i r r h o s i s o r n o n c i r r h o t i c p o r t a l h y p e r t e n s i o n , h a v eb e e n r e c o g n i z e d i n t h e c l i n ic a l l i t e ra t u r e f o r s o m e t i m ea n d g i v e n v a r io u s n a m e s , i n c l u d i n g " p o r t a l c o l o p a -t h y, ' 6 " p o r t a l h y p e r t e n s i v e c o l o p a t h y , '5 a n d " p o r t a lh y p e r t e n s i v e i n t e s t i n a l v a s c u l o p a t h y . '3 D e s c r i p t i o n s o ft h e e n d o s c o p i c a p p e a r a n c e o f t h e l e si o n s n o t e d i n t h e ses t u d i e s i n c l u d e c h e r r y r e d s p o t s ( s i m i l a r t o t h o s ed e s c r i b e d i n p o r t a l g a s t r o p a t h y ) , s p i d e r t e l a n g i e c t a s i a s ,an d ang iody sp las ia - l ike l e s ions . 2,4-6,11 M uco sa l e r y t he m a ,f r ia b i l i ty , a n d g r a n u l a r i t y s u g g e s t i v e o f c o l i t i s h a v e a l s ob e e n d e s c r i b e d i n t h e s e p a t i e n t s . 11-13 I n s o m e o f t h e s es t u di e s, f e w o f t h e p a t i e n t s u n d e r w e n t b i o p s y o f t h el e s i o n s b e c a u s e o f t h e r i sk o f b l e e d i n g . 11 H o w e v e r , i n t h ec a s es w i t h b i o p s i e s , d e s c r i p t i o n s o f t h e m i c r o s c o p i cf i n d i n g s i n c l u d e d i l a ta t i o n a n d t o r t u o s it y o f m u c o s a lv e ss e ls , as w e l l as i n c r e a s e d n u m b e r s o f s m a l l v e ss e ls w i t ht h i c k e n e d w a l l s i n t h e l a m i n a p r o p r i a . 3,5O u r r e s u l t s s h o w t h a t m u c o s a l v a s c u l a r d i l a t a t i o na n d e c ta s ia , p r e s e n t i n 7 2 % o f o u r c a s es , a r e c o m m o n i nt h e c o l o n i n p o r t a l h y p e r t e n s i o n . I n a d d i t i o n t o t h eq u a n t i t a t i v e c h a n g e s i n v a s c u l a r d i a m e t e r , q u a l i t a t i v ec h a n g e s , s u c h a s t h i c k e n i n g o f t h e v e s s e l w a ll s, i n-

c r e a s e d d e n s i t y o f s m a l l v es s el s, a n d t o r t u o u s i t y , a r e a l s op r e s e n t i n m a n y o f t h e c a s e s. L a r g e d i l a t e d v e s se l s, s o m ew i t h t h i c k e n e d w a l l s , w e r e s e e n t r a v e r s i n g t h e m u s c u l a -r i s m u c o s a e i n t o t h e l a m i n a p r o p r i a f r o m t h e s u b m u -c o s a; t h e s e v e ss e ls m o s t l i k e l y r e p r e s e n t e c t a t i c v e n u l e s .E n d o s c o p i c f i n d i n g s i n t h e s e p a t i e n t s w e r e s i m i l a r t ot h o s e r e p o r t e d i n o t h e r s t u d ie s o f p o r t a l c o l o p a t h y 4-6,11a n d i n c l u d e d p a t c h y e r y t h e m a , p u n c t a t e r e d m a c u le s ,a n d t e l a n g i e ct a s i as . N o p a r t i c u l a r c a u s e f o r t h e c i r r h o s i so f p o r t a l h y p e r t e n s i o n w a s a s s o ci a te d w i t h t h e p r e s e n c eo f p o r t a l c o l o p a t h y , a s r e p o r t e d b y o t h e r i n ve s ti g a-t o r s . 2,4,6,11 O f t h e p a t i e n t s w i t h c i r r h o s i s w h o u n d e r w e n tu p p e r G I e n d o s c o p y , o n l y th o s e w i th c o l o n i c m u c o s a lv a s c u l a r c h a n g e s h a d p o r t a l g a s t r o p a t h y . G a s t r o i n t e s t i -n a l b l e e d i n g l o c a l i z ed t o t h e l o w e r G I t r a c t w a s m o r ec o m m o n i n p a ti e n t s w it h p o r ta l c o l o p a t h y ; u p p e r g a s tr o -i n te s ti n a l tr a ct h e m o r r h a g e w as m o r e c o m m o n i n t h o s ew i t h o u t d i l a t e d c o l o n i c m u c o s a l v e s s e l s . E s o p h a g e a lv a r i c e s w e r e n o t p a r t i c u l a r l y a s s o c i a t e d w i t h p o r t a lc o l o p a t h y , a n d t h e y w e r e p r e s e n t i n m o s t p a t i e n t s w it hp o r t a l h y p e r t e n s i o n .

R e c o g n i t i o n o f t h e s e v a sc u l a r c h a n g e s o n b i o p s y o ft h e c o l o n i c m u c o s a c a n b e d i ff ic u lt . A t o n e e n d o f t h es p e c t r u m , t h e r e is c o n s i d e r a b l e o v e r l a p w it h n o r m a lv a s c u l a r a r c h i t e c t u r e , a n d i t is d i ff i c u l t i f n o t i m p o s s i b l et o r e c o g n i z e s i m p l e v a s c u l a r d i l a t a t i o n o n r o u t i n eh i s to l o g i c a l p r e p a r a ti o n s . F u r t h e r m o r e , v a s c u la r d i la t a-t i o n w i t h o u t s t r u c t u r a l c h a n g e s ( s u c h a s t o r t u o s it y a n dv e ss el w a ll t h i c k e n i n g ) i n t h e m i c r o a n a t o m y o f t h eb l o o d v e s se l s is n o t s p e c i f ic a n d c a n b e s e e n i n i n f l a m m a -t o r y d i s o r d e r s o r e v e n a s a n a r t i f a c t o f b io p s y . I n a ne f f o r t t o c l a ri f y t e r m i n o l o g y , s o m e i n v e s t i g a t o r s h a v ep r o p o s e d t h a t t h e t e r m ectasia b e r e s e r v e d f o r t h i sc o m b i n a t i o n o f d i l a ta t i o n a n d s t r u c t u ra l c h a n g e s i n

TABLE 4 . C a u s e s o f C i r r h o s i s /P o r t a l H y p e r t e n s i o nD i l a t e d S u p e r f i c ia l D i l a t e d I n t e r m e d i a t e D i l a t e d D e e p N o D i l a t e dCa use To tal Vessels Vessels Vessels Vessels

A u t o i m m u n e h e p a t i t i s 3 1 1 2 0A l c o h o l 8 3 1 4 3H e p a t i t i s B 3 0 1 2 0H e p a t i t i s C 9 1 2 4 4PBC 5 2 2 3 1PSC 3 2 2 0 0Se c o n d a ry b i l i a ry c i r rh o s i s 2 1 1 2 0N o n c i r r h o t i c P H T 2 0 1 0 0N A SH 2 1 1 2 0C ry p t o g e n i c 1 2 5 5 7 4A b b r e v i a t i o n : N A S H , n o n a l c o h o l i c s t e a t o h e p a ti t is .

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HUMAN PATHOLOG Y Volume 29, No. 5 (Ma y 1998)b l o o d v e s s el s . 3 E c t a t i c v e s s e ls , a s d e f i n e d i n t h i s w ay , c a nb e r e a d i ly r ec o g n i z e d a s a b n o r m a l o n r o u t i n e H & Eh i s t o l o g i c a l p r e p a r a t i o n s .T h e p a t h o g e n e s i s o f th e s e l e s io n s r e m a i n s u n c l e a r.H u m a n a n d a n i m a l s t u d i e s h a v e s h o w n t h a t c h r o n i cp o r t a l h y p e r t e n s i o n i s a s s o c i a t e d w i t h i n c r e a s e d b l o o df l o w t h r o u g h o u t t h e e n t i r e g a s t r o i n t es t i n a l t r ac t a n dw i t h d e c r e a s e d v a s c u la r r e s i s t a n c @ 4 a l t h o u g h o t h e ri n v e st i g at o r s r e p o r t t h a t m u c o s a l b l o o d f l ow is d i m i n -i sh ed 15,16 or tha t the m uc os a i s re la t ive ly i s ch em ic . 17,1sT h i s i n c r e a s e d v a s c u l ar p r e s s u r e m a y l e a d t o a n i n c r e a s ei n c a p i l l a r y f i l t r a t i o n a n d s u b s e q u e n t d i l a t e d v e s se l s a n dm u c o s a l e d e m a ? 4 T h i s c h r o n i c i n c r e a s e i n v a s c u l a rp r e s s u r e a l s o m a y e x p l a i n t h e t h i c k e n i n g o f sm a l lv e n u l a r w a ll s ( a r t e ri a l iz a t i o n ) n o t e d i n m a n y o f t h e s ecases .T h e v a s c u la r d i l a ta t i o n i n p o r t a l c o l o p a t h y b e a r ss o m e r e s e m b l a n c e t o t h e c h a n g e s s e e n i n a n g i o d y s p l a -s ia o f t h e c o l o n , a n d b o t h e n t it i es c a n c a u s e l o w e r G Ib l e e d i n g , s o m e t i m e s m a s s i v e . 19 N a v e a u e t a l 2 h a v es h o w n t h a t a l t h o u g h t h e l e s io n s o f p o r t a l c o l o p a t h y a res i m i l a r t o a n g i o d y s p l a s i a , t h e a n g i o d y s p l a s t i c l e s i o n sc o n t a i n e d f e w e r d i l a te d c a p i l la r ie s , a n d t h e s e w e r es m a l l e r i n d i a m e t e r . A n g i o d y s p l a s t i c l e s i o n s w e r e a l s ol es s w i d e l y d i s t r i b u t e d t h a n t h e l e s i o n s o f p o r t a l c o l o p a -t h y. 2 A n g i o d y s p l a s i a i s c o n s i d e r e d b y m a n y t o b e ad e g e n e r a t i v e p r o c e s s a t t r i b u t a b l e t o r e p e a t e d p a r t i a li n t e r m i t t e n t o b s t r u c t i o n o f su b m u c o s a l v e in s f r o m m u s -c u l a r c o n t r a c t i o n o f t h e c o l o n . 21 I n p o r t a l c o l o p a t h y , t h ei n c r e a s e d v e n o u s p r e s s u r e i s p r o b a b l y s u s ta i n e d r a t h e rt h a n i n t e r m i t t e n t a n d m a y b e o f g r e a t e r i n te n si ty , th u sl e a d in g t o m o r e p r o n o u n c e d a n d w i d e sp r e a d l es io n s.W e f o u n d t h a t a l t e r a t io n s o f c o l o n i c m u c o s a l v es -s e ls w e r e s e e n i n p a t i e n t s w i t h s i m i l a r c h a n g e s i n g a s t r icm u c o s a l v es s el s ( p o r t a l g a s t r o p a t h y ) , a l t h o u g h t h i s f i n d -i n g w a s n o t s t at is t ic a ll y s ig n i f i c a n t i n o u r s tu d y . H o w e v e r ,t h i s a s s o c i a t i o n h a s al s o b e e n r e p o r t e d b y o t h e r i n v e s ti -g a t o r s , w i t h 4 2 % t o 5 0 % o f p a t i e n t s w i t h p o r t a l c o l o p a -t h y al so h a v i n g p o r t a l g a s t r o p a t h y o n u p p e r G I e n d o s -c o p y .4'6'11 W h e r e a s i n m o s t r e p o r t s p a t i e n t s w i t h p o r t a lc o l o p a t h y a l so h a d e s o p h a g e a l v a r i c e s, 5 i n o u r s tu d y , a ne q u a l n u m b e r o f p a ti e n t s w i th e s o p h a g e a l v a ri c es d i dn o t h a v e i d e n t i f ie d v a s cu l a r c h a n g e s i n t h e c o l o n o nb i o p s y . O t h e r i n v e s t i g a t o r s r e p o r t n o c o r r e l a t i o n b e -t w e e n s e v e r it y o f e s o p h a g e a l v a r i ce s a n d p o r t a l c o l o p a -t h y. 2,11 A l t h o u g h s o m e s t u d i e s r e p o r t t h a t p a t i e n t s w i t hp o r t a l c o l o p a t h y a r e m o r e l ik e ly t o h a v e b l e d f r o me s o p h a g e a l v a r i c e s , o u r s t u d y d i d n o t s u p p o r t t h i sf i n d i n g . 5

I t h a s b e e n r e p o r t e d t h a t a l t e r a t io n s i n c o l o n i cm u c o s a l v e s s e ls c a n c a u s e c l in i c a ll y s i g n i f ic a n t G I b l e e d -i n g i n a s u b s e t o f p a t i e n ts w i t h p o r t a l h y p e r t e n s i o n y ,5,6a l t h o u g h d e t e r m i n i n g t h e l i k e li h o o d o f b l e e d i n g f r o mt h i s l e s i o n i s p r o b l e m a t i c . W e k n o w f r o m p r e v i o u ss t u d ie s t h a t t h e p r e s e n c e o f p o r t a l g a s t r o p a t h y c a n l e a dt o h e i n e - p o s i t i v e st o o l s w i t h o u t o v e r t b l e e d i n g e p i -s o d e s , 22 m a k i n g i t d i ff i c u lt t o d e t e r m i n e w h e t h e r t h es o u r c e i s t h e u p p e r o r l o w e r G I t r a c t . I n a d d i t i o n ,a n o r e c t a l v a ri ce s a n d h e m o r r h o i d s a r e v e r y c o m m o nc a u s e s o f l o w e r G I t r a c t b l e e d i n g i n c i r r h o t i c p a t i e n t s , 12a n d t h e s e l e si o n s a re a l so v e r y c o m m o n i n p a t i e n t s w it h

t h e m u c o s a l v a s c u l a r c h a n g e s o f p o r t a l c o l o p a t h y . 4,5 I no u r s t u d y , d i l a t a t i o n o f c o l o n i c m u c o s a l v e s s el s w a sa s s o c ia t e d w i t h l o w e r G I h e m o r r h a g e , a n d o t h e r i n v es ti -g a t o r s 2,3,5,6 h a v e f o u n d a s i m i l a r a s s o c i a t i o n . H o w e v e r , i nt h e m o s t s tr i k in g e x a m p l e o f p o r t a l c o l o p a t h y in o u rs tu d y , t h e p a t i e n t d i d n o t h a v e a h i s t o r y o r p r e s e n t w i t hl o w e r G I h e m o r r h a g e , a n d t h e l e si o n w as f o u n d w h e nt h e p a t i e n t u n d e r w e n t c o l o n o s c o p y f o r e v a lu a t io n o fd i a r rh e a . T h e r e f o r e , a l t h o u g h t h e c h a n g e s o f p o rt a lc o l o p a t h y m a y p o t e n t i a l ly c a u s e G I b l e e d i n g i n a s u b s e to f p a ti e n t s, d e t e r m i n i n g t h e l i k e l i h o o d o f c l in i ca l lys i g n if i c an t b l e e d i n g f o r a n i n d i v i d u a l p a t i e n t w i t h t h el e s io n r e m a i n s p r o b l e m a t i c .

S o m e e n d o s c o p i c s t u d i e s r e p o r t c h a n g e s s u g g e s -t iv e o f c o li ti s , s u c h a s m u c o s a l g r a n u l a r i t y a n d f r i a b i li t yi n p a t i e n t s w i t h p o r t a l h y p e r t e n s i o n . 6,11,12 H i s t o l o g i c a le x a m i n a t i o n o f t e n s h o w s e d e m a a n d a n o n s p e c i f i ci n c r e a s e in c h r o n i c i n f l a m m a t o r y c e ll s i n t h e l a m i n ap r o p r i a . M i n o r d i s t o r t i o n o f m u c o s a l a r c h i t e c t u r e a l soh a s b e e n r e p o r t e d . I n o u r s t u dy , f o c a l c o ll e c t io n s o fn e u t r o p h i l s w e r e s e e n i n a f ew c as es , a n d s o m e b i o p s ys p e c i m e n s s h o w e d s l ig h t m u c o s a l d i s t o r t i o n . T h e m a j o rs i g n i f i c a n c e o f t h i s f i n d i n g i s t h a t t h e s e c h a n g e s s h o u l dp r o b a b l y n o t b e i n t e r p r e t e d a s s u b t le e v i d e n c e o fu l c e r a t i v e c o li ti s , i n t h e a b s e n c e o f m o r e s u b s t a n t i a le v i d e n c e . ~,6 K o z a r e k e t a l 6 h a v e s u g g e s t e d t h a t t h ei n c r e a s e i n i n f l a m m a t o r y c e l ls m a y b e d u e t o i n c r e a s e dp e n e t r a t i o n o f g u t l u m i n a l a n t i g e n s i n t o t h e l a m i n ap r o p r i a . T h e a r c h i t e c t u r a l d i s t o r t i o n s u g g e s t s a n e l e -m e n t o f c h r o n i c m u c o s a l i s ch e m i a , a n d s t u d ie s o fm u c o s a l p e r f u s i o n i n p o r t a l g a s t r o p a t h y s u g g e s t t h a t ,d e s p i t e t h e i n c r e a s e d b l o o d f lo w , t h e g a s t r ic m u c o s a isr e l a t iv e l y u n d e r p e r f u s e d a n d i s c h e m i c J 7,1s A s i m i l a rm e c h a n i s m i n t h e c o l o n i c m u c o s a m a y b e r e s p o n s i b lef o r t h e m i n o r a r c h i t e c t u r a l c h a n g e s .

I n s u m m a r y , w e b e li e v e t h a t r e c o g n i t i o n o f t h ec h a n g e s o f p o r t a l c o l o p a t h y is im p o r t a n t , b e c a u s e t h i sl e s i o n m a y c a u s e c l i n ic a l ly s ig n i f i c a n t l o w e r G I t r a c tb l e e d i n g i n a s u b s e t o f p a t ie n t s . W e p r o p o s e t h ef o l l o w i n g s t ra t e g y a n d t e r m i n o l o g y f o r e v a l u a t i n g c o l o nb i o p s y s p e c i m e n s f r o m p a t i e n t s w i th p o r t a l h y p e r t e n -s io n . F i rs t o f a ll , w e c a n n o t o v e r e m p h a s i z e t h e i m p o r -t a n c e o f c o r r e l a t i o n w i t h c l i n i ca l h is t o r y . T o m a k em e a n i n g f u l c l i n i c o p a t h o l o g i c a l c o r r e l a t i o n s i n t h e s ep a t i e n t s , i t i s c r i t i c a l t h a t t h e p a t h o l o g i s t b e t o l d t h ei n d i c a t i o n f o r c o l o n o s c o p y a n d t h a t t h e p a t i e n t h a sc i r rh o s i s o r p o r t a l h y p e r t e n s i o n . A l t h o u g h t h e e n d o -s c o p i c f i n d i n g s a r e n o n s p e c i f i c , t h e s e s h o u l d a l s o b ec o m m u n i c a t e d , a n d t h e s it e o f b i o p s y s h o u l d b e s p ec i -f ie d . T h e p a t h o l o g is t sh o u l d c o m m e n t o n t h e p r e s e n c eo r a b s e n c e o f v a s c u la r c h a n g e s i n t h e m u c o s a , r e s e r v i n gt h e t e r m ectasia f o r v a s c u l a r d i l a t a t i o n w i t h s t r u c t u r a la b n o r m a l i t i e s . 3 T h e p r e s e n c e o f a g r a n u l a t i o n t i s s u e -l i k e p r o l i f e r a t i o n o f sm a l l t h i c k - w a l le d v e ss e ls a n d t o r t u -o u s e c t a t i c v e s s e ls is r e l a t i v e l y s p e c i f i c f o r m u c o s a lc h a n g e s c a u s e d b y p o r t a l h y p e r t e n s i o n , a a n d t h e t e r mportal colopathy s h o u l d b e a p p l i e d o n l y to t h e s e w e ll -d e v e l o p e d c h a n g e s . I t a ls o s h o u l d b e r e c o g n i z e d t h a t an o n s p e c i f i c i n c r e a s e i n c h r o n i c i n f l a m m a t o r y c e l l s i nt h e l a m i n a p r o p r i a a n d m i n o r d e g r e e s o f m u c o s ala r c h i t e c t u r a l d i s to r t i o n o f t e n a c c o m p a n y t h e s e c h a n g e s

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COLO NIC MU COSA L VESSELS N CIRRHOSIS (Lamps et al)a n d s h o u l d n o t b e o v e r i n t e r p r e t e d a s e v i d e n c e o fq u i e s c e n t u l c e r a t i v e c o l i t is .

REFERENCES1. Hosk ing SW, Sm a r t HL, Joh nso n A G, e t al : Ano re c ta l va r ic e s ,ha e m or rhoids , a nd por ta l hype r te ns ion . La nc e t 1 :349-352, 19892. G oe nka MK, Koc hha r R , Na gi B , e t a h Re c tos igm oid va ric e sa n d o t h e r m u c o s a l c h a n g e s i n p a ti e n t s w it h p o r t a l h y p e r te n s i o n . A m JGa s t roe ntero186:1185-1189, 19913. V iggia no TR, G os tout CJ : Por ta l hy pe r te ns ive in te s t ina l va sc u-lopa thy: A re v ie w of the c l in ic a l, e ndosc opic , a n d h i s topa tho logicfe a ture s. Am J Ga s t roe nte ro187:944-954, 19924. Ga nguly S , Sa r in SK, Bha t ia V , e t a l : The pre va le nc e a ndspe c t ru m of c o lonic l e sions in pa t i e n t s w i th c i r rhot i c a nd n onc i r -rhof ic por ta l hype r te ns ion . He p a to log y 21:1226-1231, 19955. Na ve a u S , Be dossa P , Poyna rd T , e t a l : Por ta l hype r te ns ivecolop athy: A new enti ty. D ig Dis Sci 36:1774-1781, 199 l6 . K oz a re k RA, Boto m a n VA, Bre dfe ld t JE , e t a h Po r ta l c o lopa -thy: Prospe c t ive s tudy of c o lon osc op y in pa t i e n t s w i th por ta l hype r te n -s ion. Gastroenterology 101:1192-1197, 19917. Mc Corm a c k TT, S im s J , Eyre -Brook I , e t a h Ga s t r i c l e s ions inpor ta l h ype r te ns ion: Inf la m m a to ry ga st ri ti s o r c onge s t ive ga s t ropa -

thy? Gu t 26:1226-1232, 19858. Mis ra SP, Dwive di M, Mis ra V, e t a h En dosc o pic a nd h i s to logica ppe a ra nc e of the ga s tr i c m uc osa in pa t i e n t s w i th por ta l hype r te n-s ion. Gastrointes t ina l Endoscopy 36:575-579, 19909. Pa pa z ia n A , Bra i l lon A , Dupa s JL , e t a l : Por ta l hype r te ns ivega s t r ic m uc osa : An e ndo sc opic s tudy . Gut 27:1199-1203, 198610. Qu in te ro E , P ique JM, B om b i JA , e t a h Ga s t r i c m uc o sa lva sc ula r e c ta s ia s c a us ing b le e ding in c i r rhos i s . Ga s t roe nte ro logy93:1054-1061, 1987

11. Ta m T -N, Ng W-W, Le e S-D: Colon ic m uc o sa l c ha ng e s inpatien ts with l iver c ir rhosis . Gastro intes t End osc 42:408-412, 199512. Scandalis N, Archimandri t is A, Kastanas K, e t a l : Colonicf indings in c i r rhot i c s w i th por ta l hy pe r te ns ion: A prospe c t ive c o lon o-sc opic a nd h i s to logic a l sm dy. J C l in Ga s t roe nte ro118:325-328, 199413. Ra binovi tz M, Sc ha de RR, D ind z a ns VJ , e t a h Co lonic d i se a sein c i r rhos i s: An e nd osc op ic e va lua t ion in 412 pa t i e n ts . G a s t roe nte ro l -ogy 99:195-199, 199014. Kvie tys PR, Gra ng e r DN: Phys io logy a nd pa thoph ys io logy ofthe c o lonic c i r c u la t ion . C l in Ga s t roe n te ro l 15 :967-983, 198615. Iwa o T , Toyona ga A , Ike ga m i M, e t a l : Re duc e d ga s t r i cm uc o sa l b lo od f low in pa t i e n t s w i th po r ta l -hype r te ns ive ga s tropathy.H e p a t o l o g y 1 8 : 3 6 4 0 , 1 9 9316. S awant P, Bha tia R, Kulhall i PM, e t a l: Com pari son of gastr icm uc o sa l b lood f low in nor m a l subje c t s a nd in pa t i e n t s w i th por ta lhype r te ns ion us ing e ndosc opic l a se r -Dopple r ve loc im e t ry [ s e e c orn-m e nts ] . India nJ Ga s t roe nte ro l 14 :87-90 , 199517. P ia se c ki C , Chin J , Gre e ns la d e L , e t a l: Endosc op ic de te c t ionof i s c ha e m ia w i th a ne w probe indic a te s low oxyge na t ion of ga s t ri cepi the l iu m in por ta l hyperten sive gastropathy. Gu t 36:654-656, 199518. Sa r fe h I , Sol im a n H , Wa xm a n K , e t ah Im p a i re d ox yge na t ionof ga s tr i c m uc o sa in por ta l hyp e r te ns ion: The ba si s for inc re a se dsusceptibi l i ty to injury . Dig Dis Sci 34:225-228, 198919. Sha rm a R , Gorbie n MJ : Angiodyspla s ia a nd lowe r ga s t ro in te s -f ina l tr a c t b le e din g in e lde r ly pa ti e n t s . Arc h In te rn Me d 155:807-812,199520. Na ve a u S , Le ge r -Ra ve t MB, Houda ye r C , e t a h Non he re di ta ryc olonic a ngiodysplas ia s: H is to m o rpho m e t r i c a pproa c h to the i r pa tho-genesis . Dig Dis Sci 40:839-842, 199521. Bole y SJ , Bra nd t LJ: Vascular ec tas ias of the c olon . Dig Dis Sci31:26S-42S, 198622. D 'Am ic o G , Mo nta lba no L , Tra ina M, e t a h Na tura l h i s tory ofc onge s t ive ga s t ropa thy in c i r rhos i s . Ga s t roe nte ro logy 99:1558-1564,1990

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