Closed hyperthermic intraperitoneal chemotherapy with open abdomen: A novel technique to reduce exposure of the surgical team to chemotherapy

drugs

Laurent Benoit, MD, Nicolas Cheynel, MD, PhD, Pablo Ortega-Deballon, MD, PhD, Giovanni Di Giacomo, MD, Bruno Chauffert, MD, Patrick at, MD!

"ervice #e Chirurgie Digestive, $horaci%ue et Canc&rologi%ue C'( #u Bocage ) B# Mal #e Lattre #e $assigny )*+,- Di.on Ce#e/, 0rance

ABSTRACT 1/2osure of the surgical team to to/ic #rugs #uring hy2erthermic intra2eritoneal chemothera2y 3'4P1C5 remains a matter of great concern! 4n close#-ab#omen '4P1C o2erating room staffs are not e/2ose# to #rugs, but the #istribution of the heate# li%ui# 6ithin the ab#omen is not o2timal! 4n o2en-ab#omen '4P1C, the o22osite is true! 1ven though the o2en-ab#omen metho# is 2otentially more effective, it has not become a stan#ar# 2roce#ure because of the risk of e/2osure of members of the team to #rugs! 7e 2resent a ne6 techni%ue 3close# '4P1C 6ith o2en ab#omen5 6hich ensures 2rotection against 2otentially contaminating e/2osure to li%ui#s, va2ours an# aerosols, an# allo6s 2ermanent access to the 6hole ab#ominal cavity! 4ts 2rinci2le is to e/ten# the ab#ominal surgical 6oun# u26ar#s 6ith a sort of 8glove-bo/9! $he cutaneous e#ges of the la2arotomy are sta2le# to a late/ :6all e/2an#er;! $he e/2an#er is #ra2e# over a s2ecial L-section metal frame 2lace# above the ab#omen! < trans2arent cover containing a : han#-access ; 2ort like those use# in la2arosco2ic surgery is fi/e# insi#e the frame! 4n *+ 2atients, this #evice 2rove# to be hermetic both for li%ui#s an# va2ours! 4ntra-ab#ominal tem2erature 6as maintaine# bet6een =) an# =>?C #uring most of the 2roce#ure! $he 6hole ab#ominal cavity 6as accessible to the surgeon allo6ing o2timal e/2osure of all 2eritoneal surfaces! $his techni%ue allo6s o2timal '4P1C 6hile limiting the 2otential to/ic effects for the surgical, me#ical an# 2arame#ical teams! Key words : Peritoneal carcinomatosis, colorectal cancer, hy2erthermic intra2eritoneal chemothera2y, to/ic effects, mutagenicity

INTRODUCTION 'y2erthermic intra2eritoneal chemothera2y 3'4P1C5 6ith surgical cytore#uction may increase survival in 2atients 6ith colorectal 2eritoneal carcinomatosis@ survival at A years is aroun# >+B in selecte# 2atients C*, )D! 7ith its 2rogressive e/2ansion C>D, the use of chemothera2y in the o2erating room raises the 2roblem of the safety of 2eo2le 2resent in the o2erating room! $his #anger remains a matter of great concern that coul# limit the e/2ansion of this other6ise beneficial techni%ue! $he to/ic an# teratogenic effects of these #rugs have been establishe# e/2erimentally, but the effects on 2eo2le han#ling them remain controversial C=D! <s 6ell as the risk of local an# general to/ic effects, 2rofessional e/2osure may in#uce obstetrical risks an# an increase# 2robability of cancer CA, ED! $here are t6o ty2es of '4P1CF one in 6hich the ab#omen is close# #uring chemothera2y 3close#-ab#omen '4P1C5 an# another one in 6hich the ab#omen is left o2en 3o2en-ab#omen '4P1C5! $he most common o2en-ab#omen techni%ue is the : coliseum techni%ue ; as #escribe# by "ugarbakerF the cutaneous e#ges of the surgical 6oun# are lifte# u26ar#s an# sus2en#e# by threa#s from a frame 2ositione# horiGontally above the ab#omen C,D! $he frame can be 2artially covere# by a 2lastic sheet but s2illage an# emanation of va2ours can not be totally controlle#! Moreover, aerosols may form CHD! $he close#ab#omen 2roce#ure avoi#s e/2osure to the chemothera2y #rugs but the #istribution of the heate# li%ui# is not uniform, 2referential circuits e/ist an# some 2eritoneal surfaces are un#ere/2ose# to chemothera2y! 7e have #esigne# a novel '4P1C techni%ue, : o2en-close# ;, 6hich combines the a#vantages of the t6o techni%ues, both o2en-ab#omen an# close#-ab#omenF o2timal e/2osure of the 2atient, minimal e/2osure of the staff to chemothera2y #rugs!

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SURGICAL TECHNIQUE $he 2rinci2le is to 2rolong the ab#ominal cavity by a sort of glove-bo/ e/ten#ing from the e#ges of the surgical 6oun#! <fter surgical cytore#uction, '4P1C is 2re2are#! $he surgeon cuts a hole in the mi##le of a sheet of late/ 3e/2an#er for '4P1C, $P*++++Lan#anger, 0rance5, 6hich has the same sha2e an# siGe of the surgical 6oun#! $he e#ges of the hole are hermetically fi/e# to the cutaneous e#ges of the la2arotomy using sta2les very close together 30igure *5! $em2erature 2robes 3one for the #ia2hragm an# one in the 2elvis5 2ass through the late/ sheet, as 6ell as inflo6 an# outflo6! $6o vertical su22orts an# t6o horiGontal arms of a $hom2son retractor 3$'++>++, Lan#anger, 0rance5 are fi/e# to the o2erating table! < s2ecial metallic frame 3he/agonal, : L ; section5 is fi/e# in a horiGontal 2osition to the t6o arms, )+ cm above the ab#omen! $he e/2an#er is 2ulle# u26ar#s through the centre of the frame! $he ti2 of the outflo6 catheter is 2ositione# bet6een the right lobe of the liver an# the #ia2hragm in or#er to 2revent a suction effect on hollo6 viscera #uring '4P1C! $he ti2 of the inflo6 catheter is 2ositione# against the insi#e face of the e/2an#er! < metacrylate trans2arent cover 6ith a *)-cm-#iameter central o2ening 3Protection Li#, $P=++++, Lan#anger, 0rance5, is smeare# 6ith an anti-fog solution! < : Gel2ort ; 3$P=*+++, Lan#anger, 0rance5, is installe# in the central o2ening of the cover! $he cover is inserte# insi#e the frame an# the late/ e/2an#er serves as a seal! Closing force2s 3$P=)+++, Lan#anger, 0rance5 fi/ the a22aratus 30igure )5! $he o2erator 6ears e/tra-long gloves 3$P)++H+, Lan#anger, 0rance5 6ith lubricant an# must make sure that all ab#ominal 2eritoneal surfaces are accessible to hisIher han#! $he ab#ominal cavity is then fille# 6ith )LIm) of #ialysis solution at >,?C! $he 2um2s are s6itche# on an# the li%ui# is heate#! <s soon as the tem2erature reaches =*!A?C the antimitotic #rug is a##e# to the circuit! 0or colon tumours an# 2seu#o-my/omas, )+ mgIm) of mitomycin C are given initially, an# then A mgIm) after >+ minutes@ the total

#uration of the '4P1C is one hour! $he intra-ab#ominal tem2erature is maintaine# bet6een =) an# =>? C throughout the 2roce#ure! $em2erature can be brought #o6n by re#ucing the inflo6 rate! $he homogeneity of the tem2erature is ensure# by constant stirring of the li%ui# 6ith se%uential o2ening of the #ifferent ab#ominal s2aces, an by moving the ti2 of the inflo6 #rain or tilting the table, accor#ing to the tem2erature gra#ient bet6een the #ia2hragm an# the 2elvis 30igure >5! $he non-submerge# e#ges of the surgical 6oun# are regularly bathe# 6ith the li%ui#! Once the '4P1C is finishe#, the li%ui# is sucke# out an# the ab#ominal cavity 6ashe#! $he skin is incise# a fe6 millimetres outsi#e its .unction 6ith the e/2an#er an# both are remove# en bloc!

RESULTS Nine 2atients 6ith colon 2eritoneal carcinomatosis an# one 6ith 2seu#omy/oma have been treate# using this techni%ue! "etting u2 the a22aratus 3e/2an#er, frame an# cover5 never took more than >+ minutes! 4ntra-ab#ominal hy2erthermia of =*!A?C 6as obtaine# in less than *A minutes an# a tem2erature bet6een =) an# =>?C 6as maintaine# #uring most of the 2roce#ure! <ll ab#ominal s2aces 6ere accessible! Jisibility through the cover 6as sufficient throughout the 2roce#ure allo6ing safe control of the viscera, inflo6 an# outflo6 at every moment! $here 6ere no flui# leaks along the sta2les line fi/ing the e/2an#er to the skin!

DISCUSSION Most cytoto/ic substances have sho6n a carcinogenic, teratogenic an#Ior mutagenic effect in e/2erimental stu#ies! Cases of skin irritation, ulcers an# even necrosis have been re2orte# follo6ing the use of these #rugs C=D! Mitomycin-C, the most 6i#ely use# agent in '4P1C, has been classifie# as a 2ossible carcinogen by the 4nternational <gency for esearch on Cancer C-D! Platinum an# its #erivatives may cause flushes, #iGGiness an# ana2hyla/is C*+D! $hree stu#ies have re2orte# a significant increase in the number of miscarriages or congenital malformation in health-care 2ersonnel e/2ose# to antineo2lasic #rugs C**-*>D! 0ive stu#ies have sho6n significant increases in the mutagenicity of urine in nurses 6orking in oncology #e2artments, but techni%ues use# to #etect cytogenetic effects or chromosomal aberrations are neither s2ecific, nor sensitive an# no formal conclusions can be #ra6n C*=-*-D! Most authors recommen# great caution 6hen han#ling these substances C*>D! 4t must be un#erline# that most of these stu#ies concerne# 2ersonnel 6ho han#le# these #rugs in centralise# units, accor#ing to very strict regulations an# un#er laminar-flo6 hoo#s! O2en-ab#omen '4P1C e/2oses o2erating room 2ersonnel to the 2otential risk of contamination by chemothera2y #rugs through the skin but also through the res2iratory, #igestive an# ocular systems 3s2ills, s2lashes, aerosols, barrier #efects in the gloves or contact 6ith va2ours 2resent in the surroun#ing air 6hen the li%ui# is heate#5 CE, )+D! Protection offere# by stan#ar# surgical masks has been #iscusse# C)*, ))D! 1yes-itching is often re2orte# by the staff #uring o2en '4P1C! $his risk is the main obstacle to the generalisation of the o2en-ab#omen techni%ue@ in 1uro2e, many teams 2erform close#-ab#omen '4P1C e/clusively for safety reasons! $here is un#eniably a feeling of insecurity!

ecent stu#ies concerning o2en-ab#omen '4P1C #i# not fin# mitomycin-C either in the o2erating room atmos2here or in the urine of the o2erating 2ersonnel! 'o6ever, the metho#s of these stu#ies 6ere not o2timal an# there 6as a lack of statistical 2o6er C)+, )), )>D! Moreover, their results #i# not reassure surgical teams 3not even the authors5, as the resulting recommen#ations 6ereF to e/clu#e from '4P1C teams 2regnant 6omen or those 6ishing to conceive, as 6ell as those breast-fee#ing, or 6ith a history of miscarriage@ to e/clu#e all 2eo2le 6ith a history of oncologic or immunosu22ressant thera2y or 6ith antece#ents of haematological #isease@ to maintain 2ositive 2ressure in the o2erating room@ to use #ouble im2ermeable gloves, goggles, 00P> masks, '1P< filters an# e/traction hoo#s C)=D@ an# to 2erform a me#ical check-u2 for the 2ersonnel every E months! Close#-ab#omen '4P1C is theoretically less satisfactory from a thera2eutic 2oint of vie6 as the li%ui# follo6s 2referential circuits bet6een the inflo6 an# outflo6 catheter CHD! "ome 2eritoneal surfaces 3mesentery, small bo6el an# retrogastric area5 are un#ere/2ose# to the heate# li%ui#! 7e aban#one# the close#-ab#omen techni%ue after a small number of 2roce#ures for this reason C)AD! 4n o2en-ab#omen '4P1C, the li%ui# can be stirre# 2ermanently allo6ing better tem2erature homogeneity, better #iffusion of the li%ui# an# #elivery of the #rugs! Only a close# system allo6ing an homogeneous #istribution of chemothera2y #rugs an# heat 6oul# 2rovi#e o2timal e/2osure of the 2atient 6ith minimal e/2osure of the 2ersonnel! Certain teams use 2lastic sheets or a rigi# enclosure 2ositione# above the ab#omen@ neither of these systems is really effective nor re2ro#ucible C)E, ),D! "ugarbakerKs coliseum techni%ue can not 2rotect accurately against s2lashes, aerosols an# va2ours!

Our : glove-blo/ ; ensures minimal e/2osure of the 2ersonnel@ but not Gero, in so far as #es2ite being 6i2e# by the gel2ort, traces of the li%ui# remain on the glove after 6ith#ra6al of the han# from the ab#omen! 0ollo6ing '4P1C, certain surgical acts 32ossible #igestive anastomosis, setting u2 #rains, 2arietal closure5 are 2erforme# once the glove-bo/ has been remove#@ the aim of 6ashing the ab#ominal cavity before removing the cover is to re#uce e/2osure of the 2ersonnel #uring this final 2hase! $here is no leakage of the li%ui# at the .oint bet6een the e/2an#er an# the skin 2rovi#e# that the sta2les are 2lace# at very close intervals! 4n so far as the e/2an#er 2rolongs the e#ges of the surgical 6oun#, the 2arietal margins can be bathe# in the li%ui#F this is im2ossible using 0u.imuraKs e/2an#er, 6hich covers the 2arietal margins C),D! Catheters an# 2robes #o not 2ass through the ab#ominal 6all before the '4P1C, thus avoi#ing also the risk of tumour recurrence in the 6all! $he ab#omen is fille# 6ith ) LIm) of li%ui# making 2ossible to obtain an a#e%uate concentration of #rugs! 7ith such a volume, the 6hole of the ab#ominal cavity 6ill be sufficiently fille# in 2rovi#e# that the e/2an#er is not 2ulle# too tight, 6hich 6oul# increase the volume of the cavity! 0rom a sub.ective 2oint of vie6, the staffKs 2erce2tion of '4P1C has totally change#F the general feeling of insecurity has #isa22eare#! $otal a##itional cost 3*=++ euros for the #is2osable kit an# )>++ euros for the metallic frame a#a2te# to the $hom2son retractor5 seems acce2table given the 2otential a#vantages in terms of safety on the one han# an# the overall cost of classical o2en-ab#omen '4P1C on the other 3calculate# at >->AH euros by 1lias et al!5 C)HD! "etting-u2 an# #ismantling times are also acce2table, given the average #uration this surgery, 6hich is a22ro/imately H hours C)-D! Late/ allergy is the only contrain#ication to the use of this #evice! Previous e/2erimental stu#ies in rats con#ucte# by our grou2 suggeste# that the close#-ab#omen techni%ue may increase 2enetration of the #rugs into the tissue thanks to a

higher 2ressure, but this has not been 2rove# in humans C>+D! 4f a higher 2ressure 6ere foun# to im2rove 2enetration of #rugs, this coul# also be achieve# using the close# o2en-ab#omen techni%ue #escribe# here! $his techni%ue combines the a#vantages of both o2en an# close#-ab#omen '4P1CF o2timal e/2osure of the 2atient 6ith minimal e/2osure of the surgical team to antineo2lasic #rugs! egar#ing the risks associate# 6ith han#ling chemothera2y agents, 0avier CED 6roteF

: $here 6ill be al6ays #oubts, an# these shoul# benefit those concerne# through a continual search for 6ays to minimiGe contact by a#a2ting 2roce#ures ;!

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