Traitement endoscopique au laser des tumeurs colo-rectales

T r a i t e m e n t e n d o s c o p i q u e au l aser des t u m e u r s c o l o = r e c t a l e s

P. S P I N E L L I , M. D A L F A N T E , E. M E R O N I

l n s t i t u t o N a z i o n a l e p e r lo S tud i o e la cura de i T u m o r i , M i l a n o ( I ta ly)

Endoscopic laser=therapy of colorectal tumours

RI~.SUME

Notre exp6rience du traitement endoscopique au laser (TEL) concerne l'emploi des lasers Nd:YAG ou Argon ainsi que le traitement endoscopique photodynamique (TEP) par laser Argon avec colorants.

De juin 1981 ~ avril 1987, 235 patients ont subi un total de 1 183 s6ances de traitement par laser Nd:YAG et Argon pour tumeurs b6nignes ou malignes et 16sions vasculaires du tractus digestif inf6rieur. Le TEL a 6tO pratiqu6 ~ titre palliatif pour tumeurs colorectales avanc6es ~ la suite d'un saignement (18 cas) ou d'une obstruction (79 cas) ; l'h6morragie a 6t6 arr(~t6e dans tous les cas et les symptOmes li6s ~ l'occlusion ont 6t6 lev6s chez 90 % des,patients.

Le traitement au laser Nd:YAG a 6t6 utilis6 ~ titre curatif chez des malades ~ haut risque chirurgical ou dans des cas bien s61ectionn6s, et les 16sions concern6es sont des ad6nomes simples ou multiples (125 patients). La disparition endoscopique et histologique des ad6nomes, pendant une pOriode d'au moins 3 mois a 6t6 obtenue dans I00 % des 16sions inf6rieures ~ I cm, 75 % des 16sions de 1 ~ 4 cm, 42 % des ad6nomes de diam(~tre sup6rieur ~ 4 cm. Des 16sions en h6morragie active ou potentielle, telles que des angiomes ou des angiodysplasies (13 patients) ont 6galement 6t6 trait6es par laser ; une h6mostase d6finitive a 6t6 obtenue dans 71% des cas.

Le laser Argon avec colorant apr6s photosensibilisation (HpD) a permis un traitement endoscopique TEP dans 7 cas de carcinome colorectal 6volu6 (traitOs entre juillet 1982 et avril 1987) : une r6ponse complete et 6 r6ponses partielles ont 6t6 obtenues.

S U M M A R Y

Our experience concerns endoscopic laser-therapy (ELT) using Nd:YAG and Argon lasers as well as endoscopic photodynamic therapy (PDT) with an Argon-Dye laser system.

Out o f 2025 laser treatments two hundred and thirty-five patients underwent a total of 1183 Nd:YAG or Argon laser treatments for malignant or benign tumors, and vascular lesions of the lower gastro-intestinal tract, from June 1981 to April 1987. E L T of colorectal advanced tumors was performed for palliation of bleeding (18 patients) and obstruction (79 patients) ; bleeding was stopped in all cases and a control of symptoms related to the obstruction was obtained in 90 % o f cases. Tumors in the initial stages were treated by Nd:YAG laser for curative purposes in high surgical risk patients or in carefully selected cases, like adenomas and adenomatosis (125 patients). The endoscopic and histological disappearance of the adenomas, for a period of at least 3 months, was obtained in 100 % of lesions smaller than 1 cm, 75 % of the 1-4 cm lesions and 42 % of adenomas larger than 4 cm. Also lesions actively or potentially bleeding, like angiomas and angiodysplasias (13 patients) were treated ; a definitive haemostasis was achieved in 71% of the cases. The Argon-Dye laser in combination with a photosensitizer (HpD) made possible the endoscopic PDT of advanced colorectal carcinoma in 7 patients (from July 1982 to April 1987) : one complete and 6 partial responses were obtained.

I N T R O D U C T I O N

L 'u t i l i s a t ion du laser a m a r q u 6 une 6 tape histo- r ique en m6dec ine . L ' a p p l i c a t i o n de la t ransmis- s ion l u m i n e u s e par f ibres op t iques a ouver t une nouve l l e 6re e n d o s c o p i q u e et con t r ibu6 h u n large emplo i du laser.

Le p r inc ipe de l ' 6miss ion de r ayons st imul6s avai t d6jh 6t6 envisag6 d6s 1917 par E in s t e in , mais l eu r i n t r o d u c t i o n dans la p r a t i que c o u r a n t e n ' a 6t6 poss ib le q u ' h par t i r de 1950 [32]. L ' e m p l o i e n d o s c o p i q u e du laser dans le t r a i t e m e n t des ma lad ies gas t ro - in tes t ina les n ' a c o m m e n c 6 q u ' u n e d iza ine d ' a n n 6 e s plus ta rd , mais son usage s 'est accru r a p i d e m e n t . Le p r e m i e r laser a 6t6 un rubis puls6, mais a c t u e l l e m e n t di f f6rents types de lasers son t d i spon ib les en m 6 d e c i n e ( A r g o n , N e o d y m i u m :

Yag, CO2, K r y p t o n , H e l i u m - N e o n et lasers h colorants ) ; en e n d o s c o p i e , deux d ' e n t r e eux sont d ' u sage c o u r a n t , h savoir A r g o n et N d : Y A G .

Le fa isceau laser est mis en place dans les cavit6s des visc6res par des f ibres i n t r o d u i t e s t ravers le cana l op6ra to i r e de l ' e n d o s c o p e . La p r inc ipa le i n t e r a c t i on du r ayon laser avec les t issus est l ' a b s o r p t i o n de la lumi6re par ceux-ci avec p o u r c o n s 6 q u e n c e u n e conve r s ion de l ' 6ne rg ie 61ec t romagnEt ique en effet t h e r m i q u e au n i v e a u de la zone oh le fa isceau du laser p r e n d con tac t avec le tissu [23] ; l ' e x t r 6me pr6cis ion du fa isceau p e u t r6dui re ce t te zone ~ un poin t . La p r o f o n d e u r de p 6 n 6 t r a t i o n du fa isceau laser est en r a ppo r t avec la l o n g u e u r d ' o n d e et le mat6r ie l cons t i tu t i f des tissus, c ' es t -h-d i re p r i n c i p a l e m e n t du sang et de l ' e a u [25]. L ' h 6 m o g l o b i n e a bso r be de fa~on s61ec-

Tir6s h part : Prof. P. SPINELLI, Istituto Nazionale per lo Studio e la cura dei Tumori, Via E. Venezian 1, 20133 Milano (Italy).

Mots-cl~s : Cancer, c61on, endoscopie, polypes, rectum, traitement au laser.

Key-words : Cancer, colon, endoscopy, laser therapy, polyps, rectum.

Acta Endoscopica Volume 17 N" 3 - 1987 157

tive les iongueurs d 'onde courtes visible ; au con- traire, l 'eau absorbe de fa~on pr6dominante les longueurs d 'onde longues infrarouge. Apr6s absorption, les radiations induisent des modifications tissulaires dues h ia chaleur et en fonction de la temp6rature , les effets obtenus vont de la coagulation des prot6ines (60 ~ ~ la carbonisation (250 ~ et ~ la vaporisation (350 ~ [26].

Les effets thermiques des lasers ont rendu possible le t rai tement de 16sions en h6morragie active ou potentiel le, telles que les angiomes, et le traitement palliatif endoscopique des tumeurs responsa- bles d 'h6morragies ou d 'obstruct ion au niveau du tractus digestif. [28].

Leur emploi est soit exclusif, soit combin6 h la radio et ~ la chimioth6rapie [7]. Des tumeurs au d6but peuvent 6tre 6galement trait6es h titre curatif, chez les patients & haut risque chirurgical, ou encore dans des cas soigneusement s61ectionn6s, parfois comme alternative aux m6thodes th6rapeu- tiques traditionnelles [11]. Le t rai tement des 16sions pr6-n6oplasiques comme les ad6nomes figure 6galement dans les possibilit6s th6rapeuti- ques du laser. En pareil cas, la photocoagulat ion au laser est effectu6e apr6s la r6section ~ l'anse diathermique. L 'emploi de certains rayons laser-en combinaison avec l 'administrat ion de substances photosensibilisatrices a rendu possible le traitement photodynamique endoscopique.

Les programmes rapport6s ci-dessous ont 6t6 mis en oeuvre dans le cadre de l 'Institut National du Cancer de Milan, dans le contexte particulier des projets ~ Power Laser >~ et ,~ Oncology ~ du Conseil National de Recherche .

MATE, R IE L E T Mff, THODES

De juin 1981 h avril 1987, sur un total de 2 025 trai tements laser 1 183 s6ances ont 6t6 appliqu6es au cours de de photocoagulat ion au laser Nd :YA G et Argon chez 235 patients, pour t ra i tement de 16sions n6oplasiques du tractus digestif inf6rieur. Le nombre des patients, group6s en fonction de la localisation et du type de cancer figure dans le tableau I. Neuf t rai tements photodynamiques par laser Argon colorant ont 6t6 r6alis6s chez 7 malades.

TABLEAU I

T R A I T E M E N T A U L A S E R N d : Y A G ET A R G O N D E 6/81 h 4/87

P O U R LI~SIONS C O L O - R E C T A L E S ( T R A I T E M E N T A L ' A R G O N INDIQUI~ P A R *)

T u m e u r s mal ignes T u m e u r s b6nignes

L6sions vasculaires

N o m b r e de pa t ien ts

97 125

13

Nombre de t ra i tements

368 785 + 9 *

6 + 15"

Le diagnostic des 16sions tumorales, malignes ou b6nignes, a 6t6 6tabli par i 'histologie.

L '6quipement laser utilis6 compor te les appareil- lages suivants : un laser Cooper Lasersonics Mod. 8000 (Santa Clara, CA. , U.S .A. ) , un laser Pilking- ton Fiberlaser (Glasgow, Angleterre) et un laser Surgical Laser Technologies (Malvern, Penn. , U.S.A.) . Le laser Argon utilis6 est un Spectra- Physics Mod. 375.

Dans tous les cas, les fibres laser utilis6es avaient un diam~tre de 400 ~t 600 microns (Quartz et Silice, Paris, France) et une longueur de 5 ~ 20 m~tres.

Les trai tements ont 6t6 appliqu6s scion la technique avec ~ absence de contact >>, maintenant la fibre h une distance d 'environ 1 cm de la cible.

Le t ra i tement pho todynamique a 6t6 r6alis6 en illuminant la surface de la tumeur au moyen de fibres de diff6rents calibres choisies en fonction de chaque cas et de la morphologie de la 16sion. La radiation en lumi6re rouge, ~ 630 nm, a 6t6 r6ali- s6e 48 & 72 heures apr6s I 'administration intravei- neuse de d6riv6s de l 'h6matoporphyr ine (HpD) la dose de 2,5-3 mg/kg.

Tumeurs malignes du tractus digestif inf6rieur

97 patients, 67 hommes et 30 femmes, ont 6t6 trait6s par laser N d : Y A G au cours de 368 s6ances, pour cure palliative d 'obstruct ion (79 cas) ou de saignements (18 cas) dus ~ des tumeurs malignes colorectales. L'glge moyen des patients est de 77 ans (limites 22-91 ans).

Les tumeurs 6taient principalement localis6es au niveau rectal (64 % ) ; 95 tumeurs sur 97 6taient des ad6nocarcinomes (tableau II).

TABLEAU II

T U M E U R S M A L I G N E S D U T R A C T U S D I G E S T I F INFI~RIEUR TRAITI~ES P A R L A S E R N d : Y A G

(98 LI~SIONS C H E Z 97 P A T I E N T S )

Canal anal

Rec tum Jonct ion recto-sigmoi- d ienne Sigmoide C61on descendan t C61on t ransverse C61on ascendant A n a s t o m o s e (r6section ant6rieure)

Total

T u m e u r s obstruct ives

2 *

48

6 11

1 1

11

8O

T u m e u r s h6morrag iques

15 w

1

m

1

1

18

Classification histologique : 95 ad6nocarcinomes. 1" cancer 6pidermoide. 1w m61anome malin.

1 5 8 V o l u m e 1 7 - N ~ 3 - 1 9 8 7 A c t a E n d o s c o p i c a

Ad6nomes ad6nomatose familiale du tractus digestif inf6rieur

A d d n o m e s

Dans not re service, les ad6nomes colorectaux sont enlev6s par r6section endoscopique h l 'anse dia thermique. Les 16sions planes, dont l 'ex6r6se est impossible ~ l 'anse, sont ensuite trait6es par laser N d : Y A G , apr6s ex6r6se de la part ie la plus volumineuse de la 16sion.

95 pat ients (34 h o m m e s et 61 femmes) ag6s de 43 ~ 88 ans (age moyen : 68), ont 6t6 trait6s par laser N d : Y A G au cours de 615 s6ances. L ' examen histologique des 16sions, r6alis6 sur les f ragments r6s6qu6s h l 'anse d ia thermique, a montr6 des ad6- nomes tubulaires dans 13 cas, tubulo-villeux dans 40 cas, et villeux dans 42. Des zones de malignit6 (cancer invasif) 6taient pr6sentes dans 5 cas appa~- tenant tous au groupe ad6no-villeux. Ces cas ont 6t6 trait6s par appl icat ion au niveau de la base de r6section, d 'un r a y o n n e m e n t laser N d : Y A G . Dans t o u s l e s cas, le choix du t ra i tement endoscopique a 6t6 d6cid6 apr~s exclusion du recours ~ la chirurgie, h la suite d ' une consultat ion multidisciplinaire.

A d ~ n o m a t o s e f a m i l i a l e

La polypose colique familiale est en g6n6ral trait6e par co lec tomie et anas tomose il6o-rectale ; la surveillance et le t ra i tement des ad6nomes r6si- duels au n iveau du moignon rectal est r6alis6e par voie endoscopique . Le t ra i tement par laser a 6t6 accompli chez 30 pat ients (20 hommes , 10 femmes) glg6s de 15 ~ 50 ans (age moyen : 30,9).

La cure par laser N d : Y A G a 6t6 pr6f6r6e dans 170 t ra i tements et celle par laser Argon dans 9. Le choix du type de laser est d6termin6 par les sensations douloureuses du patient au cours du t ra i tement des ad6nomes par N d : Y A G ; le laser Argon a une puissance de p6n6trat ion moindre et pour cette raison, ent ra ine moins de douleurs pour le patient.

Les t ra i tements laser ont 6t6 r6alis6s ~ des inter- valles de trois m o i s : dans un nombre limit6 de cas, l ' intervalle a 6t6 port6 h six mois en raison du petit n o m b r e d ' a d 6 n o m e s et du long d6placement des patients. Nous avons photocoagul6 jusqu 'h 30 16sions po lypoides au cours de chaque s6ance. Tant chez les pa t ients atteints de polypose familiale que chez les por teurs d ' ad6nomes simples, des biopsies ont 6t6 pr61ev6es avant t ra i tement au laser afin de contr61er l 'histologie des 16sions.

Angiomes et angiodysplasie

Ce groupe r6unit les patients trait6s par laser pour angiomes gastro-intest inaux. 15 angiomes ont 6t6 trait6s chez 7 pat ients , six malades trait6s pour angiodysplasie (non n6oplasique) ne sont pas consi- d6r6s. Tous les malades pr6sentaient des signes de r6cidive h6morrag ique (an6mie sid6rop6nique, asth6nie, per te pond6ra le) , mais dans t o u s l e s cas les 16sions 6taient trait6es en dehors de la phase

h6morragique. En tout , 12 t ra i tements par laser ont 6t6 accomplis : 4 au laser N d : Y A G et 8 au laser Argon.

Traitements photodynamiques avec HpD et laser Argon-colorant

De juillet 1982 ~ avril 1987, 9 t ra i tements photodynamiques avec H p D et laser Argon-co lo ran t ont 6t6 r6alis6s chez 7 patients (3 h o m m e s et 4 f emmes) , ag6s de 33 A 93 ans. Toutes les 16sions 6taient loca lement ~ un stade avanc6, inop6rables en raison d 'une diffusion m6tastat ique ou d 'un contexte m6dical associ6. La surface tumora le trai- t6e a vari6 de 2 ~ 6 cm 2 et le r ayonnemen t laser a 6t6 utilis6 avec une puissance variant de 60 ~ 250 mW/cm 2. Chez deux patients , le t ra i tement photodynamique a 6t6 r6p6t6 un mois plus tard dans le but de r6duire encore la masse tumorale . Dans ces deux cas, la puissance utilis6e a vari6 de 160 ~ 500 mW/cm 2.

R I ~ S U L T A T S

Tumeurs malignes

Les donn6es concernan t les param6t res de traitements au laser, le n o m b r e de s6ances et le t emps n6cessaire pou r obteni r la reperm6abi l isa- tion ou l 'h6mostase , sont fournies dans le tableau I I I .

TABLEAU III

TRA1TEMENT ENDOSCOPIQUE AU LASER Nd:YAG DANS LES TUMEURS OBSTRUCTIVES (N = 79)

OU HI~MORRAGIQUES (N = 18) DU TRACTUS DIGESTIF INFERIEUR

VALEURS MOYENNES ET LIMITES DONNI~ES ENTRE PARENTHI~SES

Nombre de s6ances . Jours Energie totale (en Joules) .

Tumeurs obstructives

1.7 (1-7) 8.7 (1-112)

11,406 (694-61,775)

Tumeurs h6morragiques

1.1 (1-2) 2.4 (1-24)

4,929 (1,109-15,601)

En cas de st6nose serr6e, le t ra i tement par laser a 6t6 pr6c6d6 d 'une dilatation m6canique. Le con- tr61e des s y m p t 6 m e s dus h l 'obstruct ion a 6t6 ob tenu dans 90 % des~cas trait6s et le sa ignement dfi au cancer a 6t6 in t e r rompu dans t o u s l e s cas. N6anmoins , la r6cidive symptomat ique li6e au cours 6volutif de la malad ie s 'est manifest6e apr~s un intervalle de 8 ~ 16 semaines dans 66 % des cas trait6s pou r obst ruct ion et 50 % des cas trait6s pour h6mostase . En cas de r6cidive, le t r a i t ement laser a 6t6 repris. Un seul pat ient a dfi subir une colos tomie de d6charge en raison d 'un 6chec de reperm6abi l i sa t ion endoscopique .

Deux h6morrag ies sont survenues en cours de t ra i tement et ont 6t6 contr616es par coagulat ion

Acta Endoscopica Volume 17 N ~ 3 - 1987 159

endoscopique ult6rieure, deux h6morragies tar- dives (7 et 14 jours apr~s le traitement) ont n6ces- sit6 des transfusions, et deux perforations ont 6t6 soumises h un trai tement conservateur (antibioti- ques et arrEt de la nutrit ion ent6rale). Une perforation, survenue au-dessus du cul-de-sac p6rito- n6al, a n6cessit6 une suture chirurgicale.

La morbidit6 totale de la m6thode est de 7 sur 97 cas (7,2 %). Aucun d6c6s n'est attribuable des complications.

Ad6nomes et ad6nomatoses

A d d n o m e s

35 % des 16sions avaient un diam~tre sup6rieur 4 c m ; 44 % 6taient villeuses (tableau IV). La

disparition macroscopique et histologique des ad6- nomes pendant une p6riode d 'au moins 3 mois a 6t6 obtenue dans tous les cas de 16sions dont le diam~tre initial 6tait inf6rieur ~ 1 cm, dans 40 cas sur 53 de diam6tre 1 h 4 c m e t dans 14 sur 33 cas de 16sions dont le diam6tre d6passait 4 cm. Le nombre de s6ances, l '6nergie appliqu6e et la dur6e des traitements sont strictement en rapport avec les dimensions initiales des ad6nomes. Le tableau V rapporte les donn6es relatives aux cas gu6ris sur le plan macroscopique et histologique, dont la surveillance est rest6e n6gative pour une p6riode d 'au moins 3 mois. Les ad6nomes sont r6partis en 3 groupes en fonction de leur taille.

TABLEAU IV

DIMENSIONS ET DIAGNOSTIC HISTOLOGIQUE DES ADI~NOMES DU TRACTUS DIGESTIF INFI~RIEUR

TRAITI~S PAR LASER C H E Z 95 PATIENTS

Dimensions Histologie

Moins d'l cm = 9 Tubulaires = 13 1 ~ 4 cm = 53 Tubulo-villeux = 40 Plus de 4 cm = 33 Villeux = 42 *

Zones de cancer invasif dans 5 cas.

TABLEAU V

TRAITEMENTS AU LASER DES ADI~NOMES COLO-RECTAUX *

L6sions gu6ries Nombre de sEances

Energie/s6ance (Joules) Dur6e du traitement (semaines)

Groupe 1 Groupe 2 Groupe 3

9/9 1

(1-12) 4,340

(1,098-5,484) i 1 jour (0-73)

40/53 2

(1-13) 2,950

(627-9,290) 9

(0-128)

14/33 6.5

(3-21) 4,322

1,643-9,889) 51.5

(6-148)

Groupe 1 = ad6nomes de moins d'l cm. Groupe 2 = ad6nomes de 1 /t 4 cm. Groupe 3 = ad6nomes de dimensions sup6rieures ~ 4 cm. * Valeurs des moyennes avec limites entre parenth6ses.

Dans un des cinq cas d ' ad6nome villeux porteur d 'un envahissement carcinomateux, le traitement est rest6 curatif sur le plan endoscopique et histologique au cours d 'une p6riode de surveillance de plus de 2 a n s ; dans les 4 cas restants, le traitement au laser a 6t6 un 6chec. 5 autres cancers invasifs ont 6t6 diagnostiqu6s au cours des s6ances de traitement : 4 sur ad6nome villeux, et un sur ad6nome tubulo-villeux. En tout, le diagnostic de malignit6 a 6t6 pos6 au cours des s6ances de traitement dans 5,6 % des ad6nomes b6nins, mais ce pourcentage monte ~ 10,8 % si l 'on consid6re s6par6ment les ad6nomes vitleux.

5 cas sur 9 cancers ont 6t6 soumis h une r6sec- tion chirurgicale, et 4 au trai tement endoscopique en raison d 'un risque op6ratoire 61ev6.

Les complications survenues au cours des traitements laser sont 3 h6morragies arr6t6es par injection d'6pin6phrine 1 :10000, et 3 h6morragies retard6es, survenant 7 et 14 jours apr~s le traitement et qui ont n6cessit6 des transfusions. Aucune perforation n 'a 6t6 observ6e.

A d d n o m a t o s e f a m i l i a l e

T o u s l e s cas colectomis6s avec anastomose il6o- rectale pour polypose familiale ont 6t6 soumis une surveillance du moignon rectal avec s6ances r6guli~res de photocoagulat ion au laser utilisant la technique avec << absence de contact >>. La puissance utilis6e dans ce groupe de patients est inf6- rieure ~t celle des autres traitements car l 'effet d6sir6 est une n6crose-coagulation des ad6nomes r6siduels et non leur vaporisation. Des puissances de 10-25 W ont 6t6 utilis6es pour les traitements au laser N d : Y A G , et 4-8 W pour les traitements l 'Argon.

Ces donn6es concernent 20 patients soumis une surveillance endoscopique de plus d 'un an. Au cours de la premi6re s6ance de laser, le nombre moyen d 'ad6nomes par patient 6tait de 11,8 (limites 1-34) alors qu 'au cours des s6ances ult6- rieures, chaque patient avait en moyenne 7,9 ad6- nomes (limites 0-47). Dans deux cas, respective- ment 14 et 66 mois apr6s le d6but du traitement, un cancer invasif du moignon rectal a 6t6 diagnos- tiqu6. Les patients op6r6s avaient une t6sion au stade Dukes C. Cinq 6pisodes d 'h6morragie retar- d6e ont 6t6 enregistr6s 3 ~ 14 jours apr~s le d6but du traitement, et des transfusions ont 6t6 n6ces- saires dans 3 cas. Quat re sur les cinq h6morragies sont survenues apr~s des s6ances de laser au cours desquelles plus de 25 ad6nomes avaient 6t6 trait6s.

Angiomes

Le laser N d : Y A G a 6t6 pr6f6r6 pour les 16sions de grandes dimensions et le laser Argon au niveau des sites coliques h parois minces, tel le caecum. Les patients ont 6t6 soumis h une surveillance endoscopique en moyenne de 14 mois (de 3 h 58

160 Volume 17 - N ~ 3 - 1987 Acta Endoscopica

mois) : 2 ont pr6sent6 de nouvelles h6morragies, dans un cas cons6cutives h une 16sion incompl~tement traitEe, et dans l 'autre ~ une 16sion m6con- nue pr6c6demment. Une h6mostase d6finitive a 6t6 obtenue dans 7 1 % des cas (5/7). Les puissances utilis6es 6taient respect ivement de 10-15 W pour le N d : Y A G , et 4-8 W pour le laser Argon, puisque le but du t ra i tement 6tait la coagulation et non la vaporisation des 16sions.

Traitement photodynamique

La r6ponse au t ra i tement a 6t6 consid6r6e comme complete (RC) dans les cas ofa a 6t6 obtenue la disparit ion histocytologique de la 16sion, et partielle (RP) dans le cas o/l le calibre initial de la 16sion a 6t6 r6duit de plus de 50 % ou disparition macroscopique avec examen cyto-histologique positif, et les autres cas ont 6t6 consid6r6s comme 6checs (E).

Les r6sultats dans ce groupe son t : 6 RP et 1 RC. Le dernier pat ient , initialement porteur d 'un carcinome de la jonct ion recto-sigmoidienne a 6t6 soumis h une radioth6rapie (5 000 rad) apr~s le t rai tement photodynamique . La dur6e moyenne de la surveillance de ces patients est de 6 mois (limites 2-20 mois). Aucune diff6rence dans les survies n'a 6t6 not6e en fonction de l '6nergie totale appliqu6e au niveau de la tumeur. Un 16ger saignement, sans cons6quence clinique, a 6t6 observ6 chez certains malades trait6s. Deux semaines apr~s le t ra i tement , les patients ont quitt6 l 'h6pital et leur surveillance endoscopique a 6t6 r6alis6e en ambulatoire .

D I S C U S S I O N

L6sions tumorales

Les 16sions recto-sigmoidiennes sont souvent dia- gnostiqu6es au stade symptomat ique , en particulier les signes obstructifs et par cons6quent tt un stade avanc6. Le t6nesme, l ' incontinence, la perte conti- nuelle de mucus et de sang figurent au nombre des sympt6mes non contr616s par la colostomie. Par contre, des sympt6mes tels que l 'occlusion et le saignement sur cancer colorectal peuvent 6tre trait6s par laser dans 90 h 100 % des cas. Nos r6sultats sont comparables h ceux des 6tudes mui- ticentriques, avec un contr61e du saignement et/ou de l 'obstruction dans 89 % des cas [17]. Dans notre exp6rience, con t ra i rement ~ certains auteurs [18, 20], les 16sions obstructives ont n6cessit6 un nombre de t rai tements sup6rieur, et des apports d'6nergie plus importants .

Chez un malade h haut risque chirurgical, trait6 pour 16sion obstructive du sigmoide, les pr61~ve- ments histologiques apr~s 3 s6ances de laser 6taient n6gatifs. La n6gativit6 histologique et

endoscopique a pu 6tre main tenue pendant un an. La lit t6rature rapporte 22 cas semblables [21].

Des complications ont 6t6 observ6es dans 7,2 % des cas trait6s. Ces donn6es concordent avec celles de la litt6rature [13, 17].

Une des indications du t ra i tement par laser dans les cancers du tractus digestif inf6rieur est la reperm6abil isat ion pr6-op6ratoire chez les malades en obstruct ion [6, 13]. Cet te m6thode permet une pr6parat ion pr6-op6ratoire , et 6vite une colostomie de d6charge. La mortalit6 op6ratoire des malades trait6s par r6section apr~s t ra i tement au laser est de 3,5 % [13], ce qui const i tue une proport ion ne t t ement inf6rieure ~ celle des patients op6r6s sans pr6parat ion colique : 22 % [12].

Ad6nomes et ad6nomatose familiale

Le t ra i tement de choix des polypes ad6noma- teux du rectum et du c61on est la r6section endoscopique h l 'anse d ia thermique [4]. Diverses m6thodes chirurgicales et endoscopiques ont 6t6 sugg6r6es pour le t ra i tement des polypes ad6noma- teux qui ne peuvent pas 6tre r6s6qu6s h l'anse.

Les ad6nomes villeux et tubulo-villeux du rectum qui ne peuvent pas 6tre r6s6qu6s par voie endoscopique, et le sont par des interventions res- pectant le sphincter, ont un taux de r6cidives de 23 % dans les deux a n s ; des complications chez 12 % des patients s 'a joutent au taux de r6cidives et h une mortalit6 op6ratoire de 2,5 % [33]. M6me apr~s r6section endoscopique consid6r6e comme complete sur le plan macroscopique, les r6cidives s 'observent dans 2 1 % des cas. N6anmoins, ce pourcentage varie selon le type histologique des ad6nomes, allant de 10 % pour les non-villeux 3 1 % pour les ad6nomes viUeux [8]. Les ad6nomes non-r6s6cables h l 'anse, et les ~lots tissulaires ad6- nomateux r6siduels apr~s 61ectro-r6section peuvent 6tre photocoagul6s. D'apr~s notre exp6rience, le diam~tre initial des 16sions trait6es par laser cons- t i tue le param~tre h part ir duquel d6terminer le taux de succ~s : de 100 % pour les ad6nomes de diam~tre inf6rieur h 1 cm ~ 75 % pour ceux d ' l 4 cm, et 42 % pour ceux de dimensions sup6- rieures. La dur6e du t ra i tement et le nombre de s6ances sont 6galement li6s de faqon 6troite ~ la dimension des ad6nomes.

Dans l 'ensemble, sans consid6rer le diam~tre des 16sions, le taux de succ~s total est de 66,3 %. Ces donn6es concordent avec une 6tude internationale por tant sur 280 malades pour lesquels le taux 6tait de 6 1 % [15]. Dans 40 % des cas trait6s avec succ~s, une r6cidive a 6t6 diagnostiqu6e apr~s un intervalle moyen de 42 semaines. Les r6cidives sont plus fr6quentes dans le groupe des ad6nomes de grandes dimensions. Brune taud et al. [3] ont rappor t6 un nombre moindre de r6cidives (19 %), mais l ' intervalle de contr61e 6tait inf6r ieur : 29 semaines. Dans l 'exp6rience de Mathus-Vliegen et al. [19], le taux de r6cidives est de 52 % apr~s un

Acta Endoscopica V o l u m e 17 N ~ 3 - 1987 161

intervalle de 23-26 semaines. Des biopsies pr61e- v6es en cours des s6ances de trai tement, ont dia- gnostiqu6 une 16sion maligne dans 5,6 % des ad6- nomes villeux ou tubulo-villeux. L 'exp6rience d 'autres auteurs [19] donne un taux de 7,9 %. I1 est possible que des zones de malignit6, d6j/~ pr6- sentes au niveau de l 'ad6nome, n 'aient pas 6t6 identifi6es auparavant par la biopsie. I1 est en effet bien connu que les biopsies endoscopiques ne permet tent pas un diagnostic d6finitif tant que la totalit6 du polype n 'a pas 6t6 r6s6qu6.

La surveillance endoscopique du moignon rectal avec t rai tement au laser chez les patients soumis /~ une colectomie avec anastomose il6o-rectale, est actuellement admise comme moyen de contr61e. Au cours de cette p6riode de trai tement, le nombre moyen de polypes varie de 11,8 ~ 7,9 par patient, et dans deux cas nous avons not6 leur disparition ; deux ad6nocarcinomes sont apparus dans ce groupe de malades.

Dans notre Unit6, des th6rapeutiques de rechange sont actuellement sous 6valuation. Le traitement photodynamique avec H p D semble applicable ~ de tels malades, et les 6tudes exp6ri- mentales ont montr6 apr6s administration intravei- neuse de la substance photosensibilisatrice (HpD) son accumulat ion au niveau du tissu ad6nomateux [1, 2, 51.

A n g i o m e s et a n g i o d y s p l a s i e s

La photocoagula t ion des 16sions h6morragiques peut 6tre r6alis6e avec les lasers N d : Y A G et Argon. L'efficacit6 du laser Argon dans la r6duc- tion de la r6cidive h6morragique au niveau de 16sions avec vaisseaux apparents semble inf6rieure

celle du laser N d : Y A G [31]. La p6n6tration plus profonde du rayonnement h 1 060 nm semble res- ponsable des meilleurs r6sultats. Le risque de perforation parait limit6 au niveau des visc6res dont la paroi est suffisamment 6paisse : le taux de perforations cliniquement d6celables est de 1 % de

l 'ensemble des cas trait6s par laser N d : Y A G (14). Les angiomes et angiodysplasies sont une d6cou- verte endoscopique rare. Frfimorgen [9] sur 6 000 coloscopies donne un taux d 'anomalies vasculaires de 0,3 %. Rutgeerts et al. [22] ont montr6 que le traitement de telles 16sions vasculaires par laser N d : Y A G r6duit significativement la fr6quence des saignements. Dans notre exp6rience, 7 1 % des malades trait6s pour 16sions angiomateuses n 'on t plus eu d 'h6morragie apr6s une p6riode moyenne de surveillance de 14 mois. Nous donnons la pr6- f6rence au laser N d : Y A G dans les 16sions de grandes dimensions, et le laser Argon pour le traitement des 16sions vasculaires au niveau de segments coliques h parois minces, tel le caecum.

Plusieurs solutions de rechange h la photocoagulation au laser ont 6t6 propos6es, parmi lesquelles la plus efficace semble 6tre l '61ectrocoagulation bipolaire (bicap) et h idroprobe (EHT : sonde 61ec- t ro-hydro-thermique), et un certain nombre d 'auteurs les pr6f6rent au laser, en raison de leur moindre cofit et de leur commodit6 de trans- port [10, 16].

T r a i t e m e n t p h o t o d y n a m i q u e

Une 6tude internationale r6cente a montr6 que le traitement endoscopique de photodynamique des tumeurs pouvait 6tre utilis6 ~ un stade avanc6 dans 80 % des cas et h un stade ~< pr6coce >> dans environ 20 % des cas [30].

Notre exp6rience, commenc6e en 1982 [24, 27, 29] concerne le t rai tement de 30 patients. Les taux de tumeurs 6volu6es et de tumeurs au stade pr6- coce sont respect ivement de 56 et 44 %. Les meilleurs r6sultats ont 6t6 obtenus sur les tumeurs superficielles, avec un taux de 86 % de gu6risons compl6tes ~ 8,5 mois. C'est pourquoi, en pratique courante, le t rai tement photodynamique est parti- culi6rement applicable aux tumeurs h u n stade ~ pr6coce ~>, et chez les patients qui ne peuvent pas 6tre soumis ~ la chirurgie pour des raisons de mauvais 6tat g6n6ral ou de haut risque op6ratoire.

REFERENCES

1. BO'ITIROLI G., DAL FANTE M., SPINELLI P. - - Comparative analysis of HpD fluorescence in adenoma and adenocarcinoma of the bowel. Lasers Med. Sci., 1986, 1, 306-307.

2. BOq-TIROLI G., DAL FANTE M., SPINELLI P. - - HpD fluorescence emission samples of human pre-malignant and malignant lesions of the bowel. Proceedings of ECOOSA'86, SPIE Publ. 1987, 320-323.

3. BRUNETAUD J.M., MOSQUET L., HOUCKE M., SCOPELLITI J.A., RANCE F.A., CORTOT A., PARIS J.C. - - Villous adenomas of the rectum. Results of endoscopic treatment with Argon and Nd:YAG lasers. Gas- troenterol., 1985, 89, 832-837.

4. CURTISS L.E. - - High frequency currents in endoscopy : a review of principles and precautions. Gastrointest. En- dosc., 1973, 20, 9-12.

5. DAL FANTE M., SPINELLI P., BOTI'IROLI G. - - Hematoporphyrinderivative distribution in adenomas and adenocarcinomas of the colon: a microfluorimetric study. Lasers Surg. Med., 1987, 7, 111.

6. ECKHAUSER M.L. - - Endoscopic laser vaporization of obstructing left colonic cancer to avoid decompressive colostomy. Gastrointest. Endosc., 1987, 33, 105-106.

7. FLEISHER D. - - Laser may have uses in bladder tumors, esophageal blockage. Jama, 1985, 253, 1841-1843.

8. FROHMORGEN P. - - Endoscopic treatment of non-neoplastic stenoses and benign tumors in the lower gastrointestinal tract. Endoscopy, 1986, 18 (suppl. 1), 66-68.

9. FROHMORGEN P., LAUDAGE G., MATEK W. - - Ten years of colonoscopy. Endoscopy, 1981, 13, 162-168.

10. FROHMORGEN P., MATEK W. - - Electro-hydro-


thermo- and bipolar probes. Endoscopy, 1986, 18 (Suppl. 2), 62-64.

11. G L U C K M A N J.L. , W E I S S L E R M.C. - - Role of photodynamic therapy in the m a n a g e m e n t of early cancers of the upper aerodigest ive tract. Lasers Med. Sci., 1986, 1, 217- 220.

12. IRVIN G . L . , H O R S L E Y S., C A R U A N A J .A. - - The morbidity and mortal i ty of emergen t opera t ions for colorectal disease. Ann. Surg., 1984, 199. 598-603.

13. K I E F H A B E R P . , K I E F H A B E R K . , H U B E R F . - - Preo- perative N e o d y m i u m - Y A G laser t rea tment of obstructive colon cancer. Endoscopy, 1986, 18 (Suppl. 1), 44-46.

14. K I E F H A B E R P., K I E F H A B E R K., H U B E R F., N A T H G. - - Endoscopic N e o d y m i u m : Y A G laser coagulat ion in gastrointest inal hemorrhage . Endoscopy, 1986, 18 (Suppl. 2), 46-51.

15. L O F F L E R A. , D I E N S T C., V E L A S C O S.B. - - Interna- tional survey of laser therapy in benign gastrointestinal tumors and s tenoses . Endoscopy, 1986, 18 (Suppl. 1), 62- 65.

16. M A T E K W. , D E M L I N G L. - - Hemostas is . Therapeut ic al ternatives to the laser. Endoscopy, 1986, 18 (Suppl. 1), 17-20.

17. M A T H U S - V L I E G E N E . M . H . , T Y T G A T G.N.J . - - Laser ablation and palliation in colorectal malignancy. Resul ts of a mul t icenter inquiry. Gastrointest. Endosc., 1986, 32, 393- 396.

18. M A T H U S - V L I E G E N E . M . H . , T Y T G A T G.N.J . - - Laser photocoagula t ion in the palliation of colorectal malignancies. Cancer, 1986, 57, 2212-2216.

19. M A T H U S - V L I E G E N E . M . H . , T Y T G A T G.N.J . - - N d : Y A G laser photocoagula t ion in colorectal adenoma. Evaluat ion of its safety, usefulness and efficacy. Gastroente- rol., 1986, 90, 1865-1873.

20. M A T H U S - V L I E G E N E . M . H . , T Y T G A T G.N.J . - - N d : Y A G laser photocoagula t ion in gas t roen te ro logy : its role in palliation of colorectal cancer. Lasers Med. Sci., 1986, 1, 75-80.

21. RUSSIN D.J . , K A P L A N S .R. , G O L D B E R G R.I . , BAR- KIN J . S . - - N e o d y m i u m - Y A G laser. A new palliative tool in the t r ea tmen t of colorectal cancer. Arch. Surg., 1986, 121, 1399-1403.

22. R U T G E E R T S P., Van G O M P E L F., G E B O E S K., V A N - T R A P P E N G. , B R O E C K A E R T L., C O R E M A N S G. - - Long te rm results of t rea tment of vascular ma l fo rmat ions of the gastrointest inal tract by Neodyn ium Y A G laser photoeoagula t ion . Gut, 1985, 26, 586-593.

23. SP INELLI P . - - Applicazioni endoscopiehe dei laser. Archivio ed atti della Societh Italiana di Chirurgia. 85 ~ Congresso , Pa lermo, 12-15 ot tobre 1983. Masson , Milano, 1984, 39-46.

24. SP INELLI P . - - Endoscopie au laser avec f luorescence et photochimioth6rapie du cancer. Acta Endosc., 1983, Vol. 13, 3, 201-205.

25. SP INELLI P. - - Laser in Endoscopy. In : Emerging Tech- nologies in Surgery. L. Angelini , G. Fegiz, P .N.T. Wells Eds . , Masson , Milano, 1984, 187-190.

26. SP INELLI P . - - Le applicazioni endoscopiche del laser. Medico e Paziente , IX, 1983, 5, 178-193.

27. S P I N E L L I P., A N D R E O L A S., M A R C H E S I N I R. , MEL- LONI E. , M I R A B I L E V. , P I Z Z E q q ' I P., Z U N I N O F. - - Endoscopic HpD- lase r photoradia t ion therapy (PRT) of cancer. I n : Porphyrins in Tumor Phototherapy, A. An- dreoni , R. C u b e d d u Eds . , P lenum Publ. Co. , 1984, 423- 426.

28. S P I N E L L I P., D A L F A N T E M. - - Endoscopic laser photocoagula t ion in onco logy : a 5-year experience. Lasers Surg. Med., 1987, 7, 99.

29. S P I N E L L I P., D A L F A N T E M. - - Pho todynamic therapy in G.I . tract. Acta Endosc., 1985, 15, 69-70.

30. S P I N E L L I P., D A L F A N T E M. - - Pho todynamic therapy in the digestive tract : an internat ional enquiry . In : Laser Optoelectronics in Medicine. W. Waidel ich, P. Kiefhaber Eds . , Spr inger-Verlag, 1986, 450-457.

31. S W A I N C.P. - - Forrest II bleeding : indications for treat- men t and results of laser therapy. Endoscopy, 1986, 18 (Suppl. 1), 14-16.

32. S W A I N P. - - Laser photocoagula t ion. In : Gastrointestinal Endoscopy. Advances' in Diagnosis and Therapy. Vol. 1. P .R. Sa lmon ed. , C h a p m a n and Hall Medical , Lo n d o n , 1984, 49-57.

33. T H O M S O N J.P.S. - - T rea tmen t o f sessile villous and tubulo- villous adenomas of the r e c t u m : exper ience of S t .Mark ' s Hospi ta l , 1963-1972. Dis. Col. Rect., 1977, 20, 467-471.

I N T R O D U C T I O N

Lasers represent an historical step for Medicine. The application o f optic fibers for transmission of light was responsible for the beginning of a new age o f Endoscopy and a widespread use of lasers.

The principles of stimulated emission of radiation were predicted by Einstein as early as 1917, but it was only in the 1950s that they were available for practical use [32]. The endoscopic use o f laser in the treatment o f gastro-intestinal diseases began in the last decade and is rapidly increasing. The first practical laser was a pulsed ruby laser, but nowa- days different lasers are available in Medicine (Argon, Neodymium:YAG, C02, Krypton, Helium- Neon and Dye lasers) ; in endoscopy two of them are commonly used, i.e. Argon and N d : Y A G laser.

The laser beam is delivered into the cavities of the body by an optic fiber passing through the

operative channel of the fiberscope. The most important interaction o f laser radiation with tissue is the absorption of the light by the tissue with the consequent conversion of electromagnetic energy to thermal energy in the area where the laser beam hits the tissue [23] ; the high precision of the beam can reduce this area to a point. The depth of penetration o f the laser beam is related to beam wavelength and to materials found in tissues, that is mainly blood and water [25]. Hemoglobin selec- tively absorbs short visible wavelengths ; water, on the contrary, has a high absorption for long infrared wavelengths. Once absorbed, the radiation induces tissue modifications due to heating : according to temperature, these modifications range from protein coagulation (60 ~ to carbonization (250 ~ and vaporization (350 ~ [26].

With the thermal lasers, the treatment o f lesions actively or potentially bleeding, like angiomas, and the endoscopic palliation of bleeding or obstruction caused by tumors in the digestive tract, are pos-

Acta Endoscopica Volume 17 iV" 3 - 1987 163

sible (28 ) . They are used as the only therapeutic resource or in combination with the radio- and chemo-therapy [7]. Tumors in the initial stages have also been treated, for curative purposes, at first only in patients at high surgical risk, but subse- quently also in carefully selected cases, sometimes as an alternative to traditional methods of therapy [11] . The treatment of pre-malignant neoplasms such as adenomas also falls into this categ- ory of indications. In these cases, laser photocoagulation is carried out after electroresection with a diathermic snare. In combination with the administration of photosensitizing substances, particular laser lights have made possible the endoscopic application of photodynamic therapy.

Our programs have been developed at the National Cancer Institute of Milan, in the context of the ,, Power Laser ~ and ,~ Oncology ~ special projects of the National Research Council.

P A T I E N T S A N D M E T H O D S

Out of 2025 laser treatments performed from June 1981 to April 1987, a total of 1183 sessions of laser photocoagulation with Nd:YAG or Argon have been performed in 235 patients, for treatment of neoplasms of the lower gastro-intestinal (G.1.) tract. The number of patients, grouped according to the site and type of neoplasms is shown in table 1. Nine photodynamic treatments with the Argon-Dye laser were performed on 7 patients.

TABLE I

TREATMENTS WITH Nd:YAG AND WITH ARGON LASER FROM 6/18 TO 4/87,

IN THE COLON-RECTUM (THE TREATMENTS WITH ARGON ARE INDICATED BY *)

Malignant tumors Benign tumors Vascular lesions

Number of patients

97 125

13

Number of treatments

368 785 + 9 *

6 + 1 5 "

All the tumoral lesions, malignant or benign, were documented h&tologically.

The Nd:YAG laser equipment used was: a Cooper Laser Sonics mod. 8000 (Santa Clara, CA., U.S.A.), a Pilkington Fiberlaser 100 (Glas- gow, England) and a Surgical Laser Technologies CL40 (Malvern, Penn., U.S.A.). The Argon laser used was a Spectra-Physics mod. 375.

In all cases, laser fibers 400 or 600 microns in diameter (Quartz & Silice, Paris, France) and from 5 to 20 meters in length were used.

The treatments were carried out using a ,~ non- contact ,, technique, keeping the fiber at a distance of about 1 cm from the target.

The photodynamic therapy was carried out by illuminating the surface of the tumor with fibers of different shape, selected in each case on the basis of the shape of the lesion. The radiation with red light, at 630 rim, was performed 48-72 hours after the intravenous administration of hematoporphyrin- derivatives (HpD) in a dosage of 2.5-3 mg/kg.

Malignant tumors of the lower G.I. tract

Ninety-seven patients, 67 male and 30 female, were treated with Nd:YAG laser in the course of 368 laser sessions, for palliation of obstruction (79 cases) or bleeding (18 cases) caused by malignant tumors of the colon-rectum. The average age of these patients was 77 (range 22-91). The tumors treated were located predominantly in the rectum (64 %) ; 95 out of 97 were adenocarcinomas (table II).

TABLE II

MALIGNANT TUMORS OF THE LOWER G.I. TRACT, TREATED WITH ND:YAG LASER

(98 LESIONS IN 97 PATIENTS)

~nai canal [ectum

Rectal-sigmoid junction ;igmoid )escending colon "ransverse colon

~scending colon knastomosis (anterior

resection)

"otal

Obstructing tumors

2 *

48 6

11 1 1

11

80

Bleeding tumors

15w 1

1

1

18

Histological classif icat ion : 95 adenoca rc . , 1" sq. cell carc . , lw mal ignant melanoma.

Adenomas and familiar adenomatosis ot the lower G.I. tract

A d e n o m a s

The colorectal adenomas are removed, in our division, using endoscopic electroresection with a diathermic snare. Flat lesions, which cannot be completely resected using the snare, are subse- quently treated with the Nd: YA G laser, after removal of bulking part of the lesion.

Ninety-five patients (34 male and 61 female) aged between 43 and 88 (average 68) were treated with the Nd:YAG laser in the course of 615 sessions. The histological examination of the lesions, carried out on the fragments removed using the diathermic snare, showed tubular adenomas in 13 patients, tubulo-villous in 40 patients, and villous in 42. Areas of malignancy (invasive carcinoma) were present in 5 cases, all within the group of villous adenomas. These cases have been treated by Nd:YAG laser radiation of the basis. In all cases, the choice of endoscopic treatment was decided after the surgical alternative had been excluded, on the basis of a multidisciplinary consultation.


F a m i l i a r a d e n o m a t o s i s

Familiar colic adenomatosis is generally treated with colectomy and ileo-rectal anastomosis ; periodic checking and the possible treatment of the adenomas remaining in the rectal stump are endoscopically performed. Laser treatments have been performed in 30 patients (20 male, 10 female) aged between 15 and 50 (average : 30.9). The Nd:YAG laser was favoured in 170 treatments, and the Argon laser in 9. The choice of the type of laser was conditioned by the feeling of pain by the patient during Nd:FAG treatment of adenomas ; the Argon laser has a lower penetration and therefore causes less pain for the patient. The laser treatments were carried out at three-month inter- vals: only in a minority of cases was the interval between treatments extended to 6 months for patients who came from distant areas and bearing a limited number of adenomas. During each session, up to 30 polypoid lesions were photocoagulated. In patients with familiar adenomatosis, as in those with single adenomas, bioptic samples were taken before laser radiation in order to check the histology of the lesions.

Angiomas and angiodysplasias

This group contains those patients who had laser treatment for gastrointestinal angiomas. Fifteen angiomas m 7 patients were treated. Six patients treated for angiodysplasia (non neoplastic condi- tion) are not considered. All the patients had symptoms of recurrent bleeding (iron deficiency anaemia, asthenia, weight loss), but in all cases the lesions treated were in a non-haemorrhage phase. In all, 12 laser treatments were carried out : 4 with the Nd:YAG laser and 8 with the Argon laser.

Photodynamic treatments with HpD and Argon-Dye lasers

From 7/82 to 4/87, 9 photodynamic treatments with HpD and the Argon-Dye laser were performed on 7 patients (3 male and 4 female), aged between 33 and 93. All the lesions were in a locally advanced state and were not operable due to spread metastases that could not be resected or because of concomitant medical conditions. The tumor surface treated varied from 2 to 6 cm 2 and the laser radiation was applied to it with an intensity of power of 60-250 mW/ cm 2. In two patients, the photodynamic treatment was repeated after one month with the intention of further reducing the tumoral mass. In these cases, the power applied was 160-500 mW/ cm 2.

R E S U L T S

Malignant tumors

The data concerning the parameters of the laser treatments, the number of sessions and the time

required to obtain recanalization or haemostasis, are shown in table III.

TABLE III

ENDOSCOPIC TREATMENT, USING Nd:YAG LASER, OF OBSTRUCTING (No. =. 79) OR BLEEDING (No. = 18)

TUMORS OF THE LOWER G.I. TRACT. VALUES ARE A V E RA G E AND THE RANGE IS GIVEN

IN BRACKETS

O b s t r u c t i n g Bleeding t u m o r s tumors

No. of sessions 1.7 (1-7) 1.1 (1-2) Days 8.7 (1-112) 2.4 (1-24) Total energy (Joules) 11,406 (694-61,775) 4,929 (1,109-15,601)

In some cases of narrow stenosis the laser treatment was preceded by mechanical dilation of the lumen, A control of symptoms related to the obstruction was obtained in 90 % of the cases treated and the bleeding of carcinomas was stopped in all cases. The natural evolution of the disease, however, led to recurrence of the symptoms after an interval of 8-16 weeks in 6 6 % of the patients treated for obstruction and 50 % of those treated for haemostasis. The laser treatments were repeated in these cases. Only in one patient was it necessary to perform a decompressive colostomy because the endoscopic recanalization failed.

There were two haemorrhages occurring during the treatment and being endoscopically controlled with further coagulation, two delayed haemorrhages (in days 7 and 14 of the treatment) requiring an infusional therapy, and three perforations, two of which occurred in the extra-peritoneal tract of the rectum and were treated conservatively (antibiotics and stopping of enteral nutrition). One perforation, which occurred above the peritoneal reflection, required a surgical suture.

The overall morbidity of this method was 7/97 cases (7.2 %). There was no death that could be related to the complications.

Adenomas and adenomatosis

A d e n o m a s

Thirty-five per cent were more than diameter ; 44 % were villous (table IV).

4 cm in

TABLE IV

SIZE AND HISTOLOGY OF THE ADENOMAS OF THE LOWER G.I. TRACT TREATED WITH THE LASER

IN 95 PATIENTS

Size H i s t o l o g y

Less than 1 cm = 9 Tubu la r = 13

1 to 4 c m = 53 Tubulo-vi l lous = 40

More than 4 cm = 33 Vil lous = 42 *

Areas of invasive carcinoma in cases.

Acta Endoscopica Volume 17 N ~ 3 - 1987 165

The macroscopic and histological disappearance o f the adenoma, for a period o f at least 3 months, was obtained in all the cases with lesions which were initially smaller than 1 cm, in 40/53 cases o f the 1-4 cm lesions and in 14/33 cases o f the lesions which extended over more than 4 cm. The number o f sessions, the energy applied and the duration o f treatment are closely related to the initial size o f the adenoma. Table V reports data relating to cases macroscopically and histologically cured, and with a negative fol low-up o f at least 3 months. Adenomas are divided into 3 groups according to size.

TABLE V

L A S E R T R E A T M E N T S O F C O L O R E C T A L A D E N O M A S *

Lesions cured No. of sessions

Energy/session (Joules)

Duration of treatment (weeks)

Group 1

9/9 1

(1-12)

4,340 (1,098-5,484

1 day (0-73)

Group 2

40/53 2

(1-13)

2,950 (627-9,290)

9 (0-128)

Group 3

14/33 6.5

(3-21)

4,322 (1,643-9,889)

51.5 (6-148)

Group 1 = adenomas smaller than 1 cm. Group 2 = adenomas from 1 to 4 cm. Group 3 = adenomas extended over more than 4 cm. * The values are averages and the range is given in brackets.

In one o f the five cases o f villous adenoma with areas o f invasive carcinoma an endoscopic and histological cure was obtained with a fol low-up o f more than 2 years ; in the remaining 4 the laser treatment did not succeed. Another 5 invasive carcinomas were diagnosed during one o f the treatment sessions : 4 in villous adenomas and 1 in a tubulo-villous adenoma. Overall, the diagnosis o f malignancy was made during the sessions o f treatment in 5.6 % o f the non-malignant adenomas, but the percentage rises to 10.8 % if only the villous adenomas are taken into consideration.

Five out o f 9 malignancies were subjected to surgical resection, 4 to endoscopic treatment because o f high surgical risk.

The complications arising f rom the laser treatment were 3 haemorrhages stopped with a 1:10 000 epinephrine injection, and 3 delayed haemorrhages, occurring 7-14 days after treatment and which required an infusional therapy. No perforations were observed.

Famil iar a d e n o m a t o s i s

The endoscopic treatment o f the rectal stump in patients operated on with colectomy and ileo-rectal anastomosis for familiar adenomatosis was performed with regular laser photocoagulations using the non-contact technique in all cases. The power

used on this group o f patients was lower than in other treatments since the desired effect is" the coa- gulative necrosis o f the adenomas present, and not their vaporization. Powers o f 10-25 W were used for treatments with N d : Y A G , and 4-8 W for treatments with Argon.

The data below refer to 20 patients in whom there was more than one year o f endoscopic follow- up. A t the time o f the first laser treatment, the average number o f adenomas per patient was 11.8 (range 1-34), while at the time o f the most recent treatment, each patient had, on average, 7.9 adenomas (range 0-47). In two cases, respectively 14 and 66 months after the start o f the laser treatment, an invasive carcinoma o f the rectal s tump was diagnosed. These patients were operated on and the stage was Dukes C. Five episodes o f delayed haemorrhage were recorded, 3-14 days after the treatment, and an infusional therapy was required in 3 cases. Four o f the 5 haemorrhages occurred after laser sessions in which more than 25 adenomas had been treated.

Angiomas

N d : Y A G laser has been preferred for the larger lesions, the Argon laser treatment in thin-walled bowel, such as the caecum. The patients were fol lowed up endoscopically for an average period o f 14 months (from 3 to 58 mon ths ) : 2 showed new haemorrhages due, in one case, to a lesion uncompletely treated, and, in the other, to a lesion not previously recognized. A definitive haemostasis was achieved in 7 1 % o f the cases (5/7). The power used was 10-15 W for the N d : Y A G , and 4- 8 W for the Argon laser, since the aim o f the treatment was coagulation and not vaporization o f the lesions.

Photodynamic therapy

The response to treatment was considered to be complete (CR) in the case o f endoscopic and histo- cytological disappearence o f the lesion, partial (PR) in the case where the initial size was reduced by more than 50 % or where there was macroscopic disappearance but still with positive histo-cytological findings, and as no response (NR) in the other cases. In the group treated there were 6 PRs and 1 CR. This last patient, who initially had a carcinoma of the recto-sigmoid junction, received a cycle o f radiotherapy (5,000 rad) after the photodynamic treatment. The average follow-up o f these patients was 6 months (range 2-20 months). There were no differences in survival in relation to the total energy applied to the tumor. Slight bleeding, without clinical significance, was encountered in some o f the cases treated. Two weeks after the treatment, the patients left the hospital and had endoscopic checks carried out as out-patients.


DISCUSSION

Malignant tumors

Tumors of the sigmoid and the rectum are often diagnosed by the appearance of symptoms deriving from the obstruction, and are therefore recognised at an advanced stage. Tenesmus, incontinence, con- tinuous loss of mucus and blood are symptoms not controlled by colostomy. Control of the symptoms related to obstruction or bleeding caused by colorectal carcinomas was obtained in 90 % and 100 % respectively of the cases treated with the laser. Our results are similar to those of a multi-centre study, in which palliation of the bleeding and~or obstruction was obtained in 89 % of cases [17]. Unlike the findings reported by others [18, 20], in our experience obstructing tumors required a greater number of treatments, and at a higher energy level than for the bleeding tumors.

In one patient at high surgical risk treated for an obstructing tumor of the sigmoid, the histological samples taken after 3 laser treatments gave negative results. The negative endoscopic and histological results have been maintained for a year. The litera- ture reports 22 similar cases [21].

Complications were encountered in 7.2 % of the cases treated. Corresponding data are also reported by other Authors [13, 17].

One indication of laser treatment for carcinomas of the lower G.I. tract is the pre-operative recanalization of patients with mechanical obstruction [6, 13]. This method enables the bowel to be prepared prior to the operation, thus avoiding a decompressive colostomy. The operative mortality in patients whose bowel is resected after laser treatment is 3.5 % [13], a great deal lower than that deriving from operations carried out with no preparation of the colon : 22 % [12].

Adenomas and adenomatosis

The treatment of first choice for adenomatous polyps of the colon-rectum is endoscopic electroresection using the diathermic snare [4]. Various surgical and endoscopic methods have been suggested for the treatment of adenomatous polyps which cannot be resected using the snare.

Villous and tubulo-villous adenomas of the rectum which cannot be resected endoscopically, and treated surgically by means of operations which preserve the sphincter, relapse within two years in 23 % of cases. Complications in 12 % of patients must be added to the rate of relapse, with an operative mortality of 2.5 % [33]. Even after endoscopic electroresection considered macroscopically complete, there is relapse in 2 1 % of cases. How- ever, this percentage varies with the histological type of the adenoma, going from 10 % for non- villous to 3 1 % for villous adenomas [8]. Adenomas which cannot be snare-resected and

adenomatous tissue remaining after electroresection, can be photocoaguled. In our experience, the initial diameter of the lesions treated with the laser is the parameter which, more than any other, determines the percentage of success : from 100 % recovery for adenomas of less than a centimetre to 75 % for those between 1 and 4, and to 42 % for those of larger size. The duration of the treatment and the number of sessions were also closely connected with the size of the adenomas.

Taken overall, the number of successful laser treatments, independently of the size of the lesions, totalled 66.3 %. These data correspond with that of an international enquiry on 280 patients in whom the percentage of recovery was 6 1 % [15]. In 40 % of the successfully treated cases, a relapse was diagnosed after an average interval of 42 weeks. The recurrences were more frequent in the group of larger-sized adenomas. Brunetaud et al. [3] reported a lower number of relapses (19 %), but the average interval was shorter: 29 weeks. In the experience of Mathus-Vliegen et al. [19], the percentage of recurrences was 52 % after an interval of 23-26 weeks. In biopsies taken during the treatment sessions, diagnosis of maligancy was made in 5.6 % of the villous or tubulo-villous adenomas. In the experience of other Authors this was found in 7.9 % of cases [19]. It is possible that areas of malignancy, already present in the adenoma, were not previously recognized in the biopsy samples. It is well known that the histological diagnosis on endoscopic biopsies often does not correspond to the definitive diagnosis on the entire polyp removed.

The endoscopic treatment of the rectal stump using laser in patients who have undergone colectomy with ileo-rectal anastomosis seems to be a prospect which is as yet far off. During the period of the treatment the average number of polyps fell from 11.8 to 7.9 per patient, and in only 2 cases we got the disappearance ; two adenocarcinomas developed in this group of patients.

Our Division is currently studying alternative methods. Photodynamic treatment with HpD and laser seems to be applicable for these patients, given that experimental data have shown an accumulation of the photosensitizer (HpD) in the adenomatous tissue after systemic administration [1, 2, 5].

Angiomas and angiodysplasias

The photocoagulation of bleeding lesions can be carried out both with the Nd:YAG laser and the Argon laser. The efficiency of the Argon laser in reducing the resumption of bleeding of lesions with visible vessel seems to be inferior to that of the Nd:YAG laser [31]. The deeper penetration of the radiation at 1,060 nm seems to justify the better results obtained. The risk of perforation seems to be limited for organs that have sufficiently thick walls: the incidence of clinical perforations with

Acta Endoscopica Volume 17 IV" 3 - 1987 167

the Nd:YAG laser is, in fact, around 1 % in the majority of cases [14]. Angiomas and angiodysplasias are rarely encountered in endoscopic cases. Out of more than 6,000 colonoscopies reported on by Friimorgen [9], the incidence of vascular anomalies was 0.3 %. Rutgeerts et al. [22] have demonstrated how Nd:YAG laser treatment for such vascular malformations is effective in reducing the incidence of bleeding. In our experience, also, 71% of patients with angiomatous lesions of the G.I. tract had no further bleeding during an average follow-up period of 14 months. We favoured the Nd: Y A G laser in the cases of lesions of larger sizes, and the Argon laser for treatment of vascular formations in the thin-walled areas, such as caecum.

Several alternative methods to laser photocoagulation have been suggested : amongst these, the most effective seem to be electric bipolar probes (bicap) and hydroassisted probes (EHT : electro- hydro-thermo-probe), to the extent that some Authors prefer them to the laser because they are

easy to use, their costs are limited, and they are easily transportable [10, 16].

Photodynamic therapy A recent international enquiry has shown how

endoscopic photodynamic therapy has been used for the treatment of tumors at advanced stages in 80 % of cases, and of those in ~ early ~ stages in about 20 % of cases [30].

Our experience, which began in 1982 [24, 27, 29], currently includes the treatment of over 30 patients. The percentages of advanced tumors and of those in the initial stages are respectively 56 % and 44 %. The best results have been obtained with superficial tumors, with 86 % of complete recoveries at 8.5 months. The current situation, therefore, is that photodynamic therapy is suitable principally for tumors in the ~ early ,, stages, in patients who cannot be operated on because of poor general conditions, or because they are at high operative risk.


Documents

Traitement endoscopique au laser des tumeurs colo-rectales