Transsphenoidal removal of huge pituitary adenomas with marked suprasellar extension: results with modified surgical technique.

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Pleasecitethisarticleinpressas:FraioliMF,etal.Transsphenoidalremovalofhugepituitaryadenomaswithmarkedsuprasellarextension: Resultswithmodiﬁedsurgicaltechnique.ClinNeurolNeurosurg(2012),http://dx.doi.org/10.1016/j.clineuro.2012.06.019

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ClinicalNeurologyandNeurosurgeryxxx (2012) xxx–xxx

ContentslistsavailableatSciVerseScienceDirect

Clinical

Neurology

and

Neurosurgery

j o u r n al ho m e p a g e :w w w . e l s e v i e r . c o m / l o c a t e / c l i n e u r o

Transsphenoidal

removal

of

huge

pituitary

adenomas

with

marked

suprasellar

extension:

Results

with

modiﬁed

surgical

technique

Mario

Francesco

Fraioli

a,∗

_,

_Elisabetta

_Catena

b

_,

_Mario

_Lecce

a

_,

_Bernardo

_Fraioli

a

a_Department_of_{Neurosciences,}_{Neurosurgery,}_University_of_Rome_“Tor_Vergata”,_Italy b_Department_of_Internal_Medicine,_University_of_Rome_“Tor_Vergata”,_Italy

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received26August2011

Receivedinrevisedform1June2012 Accepted16June2012

Available online xxx Keywords: Pituitaryadenoma Transphenoidalsurgery Cerebrospinalﬂuidﬁstula Hugeadenomas

Cranialbasereconstruction

a

b

s

t

r

a

c

t

Objective:A modiﬁed transsphenoidaltechnique toremove huge pituitaryadenomaswithmarked

suprasellarextension(4.5–8cmofmaximumdiameter)ispresented.

Methods:Thetechniqueallowedtoavoidtheoccurrenceofaprecociousdescentofthesuprasellar

cister-nalplaneintothesellarplaneduringtumourremovalanditsrelatedconsequences(incompletetumour

removal,occurrenceofcerebrospinalﬂuidleak,prolongedtimeofpostoperativestayinhospital).

Tech-niqueisperformedopeningatthebeginningonlythelateralpartsofperitumoralduramater,leavingthe

centralpartoftheduramaterinsupportofthecentralpartoftumourandsuprasellarcisternalplane.

Afterremovaloflateralpartsofthetumour,thecentralpartofperitumoralduramaterisopenedandthe

centralintra-andsupra-sellarpartsofthetumourareremoved.

Results:Totalremovalwasaccomplishedin64%and45%ingroupstwoandonerespectively.

Intraopera-tiveCSFleakoccurredin2.4%and22.5%respectivelyingroupstwoandone.PostoperativeCSFﬁstuladid

notoccuringrouptwo,whileitoccurredin7.4%ofpatientsofgroupone.Averagetimeofpostoperative

stayinhospitalwas4.3and8.2daysingroupstwoandonerespectively.

Conclusion:Thepresentedmodiﬁedtranssphenoidalmicrosurgicaltechniqueforremovalofhuge

pitu-itaryadenomasallowedtoachievebetterresultsthanpatientsoperatedbystandardtranssphenoidal

surgery.

1. Introduction

Voluminouspituitaryadenomaswithmarkedsuprasellar exten-sioncanbeeffectivelytreatedbytranssphenoidalsurgery,except forrarecasesinwhichtranscranialapproach[1,2]shouldbe per-formed.

Weselected82patientsaffectedbyhugepituitaryadenomas (sized4.5–8cmofmax.diam.)withmarkedsuprasellarextension operatedfrom1997to2008.Forty-twoofthemwereoperatedby modiﬁedtranssphenoidaltechnique,achievingbetterresultsthan theother40operatedbystandardtechnique,concerningtumour removal,occurrenceofintraoperativedamagingofsuprasellar cis-ternalplane,postoperativerhinoliquorreaandpostoperativestay inhospital.

∗ Correspondingauthorat:DepartmentofNeurosciences,Neurosurgery, Univer-sityofRome“TorVergata”ViaOxford81,00133Roma,Italy.Tel.:+390620903057; fax:+390620903056.

E-mailaddress:b.fraioli@libero.it(M.F.Fraioli).

2. Materialsandmethods

Outofmorethan1400pituitaryadenomasoperatedoninour Institute(byBernardoFraioli,ChiefofDepartmentofNeurosurgery, andMarioFFraioli,ProfessorofNeurosurgery,UniversityofRome “TorVergata”)from1983to2008,weselected2groupsofpatients affectedbyhugepituitaryadenomas(sized4–8.5cmofmax.diam.) withmarkedsuprasellarextension;intracavernoussinusextension waslessthan1cmofmaximumdiameterin26patients(13forboth groups).Theﬁrstgroupwasconstitutedby40patientsoperatedby standardmicrosurgicaltransnasosphenoidaltechniquefrom1995 to2001.Patients’agerangedfrom36 to81 years(median56.4 years).Inthesecondgroupof42patients,amodiﬁed microsurgi-caltransnasosphenoidaltechniquewasused.Patients’ageranged from32to79years(median61.3years).

2.1. Preoperativeclinicalstatus

PreoperativeclinicalstatusisreportedinTable1.Insummary, therewerenosigniﬁcantdifferencesbetweenthetwogroupsof patients.Allofthempresentedpanhypopituitarismandallneeded substitutivehormonaltherapywhichwasstartedpreoperatively in44andintheimmediatepostoperativeperiodintheother38 0303-8467/$–seefrontmatter © 2012 Published by Elsevier B.V.

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Table1

Clinicalpresentationofthe82ptientsaffectedbyhugepituitaryadenoma.

Subclinical hypopituitarism Clinical hypopituitarism Visualacuity impairment Visualﬁeld impairment Suddenunilateral amaurosis Suddenbilateral amaurosis VInerve palsy Group1 9 31 40 40 2 – 3 Group2 13 29 42 42 1 1 4

patients.In22patientsbloodhormonallevelswereindicativeof

panhypopituitarismbutsymptomsweresubclinical.Threeandfour

patientsofgroups1and2respectivelypresentedapreoperative

VInervepalsy.Allpatientsbut4weresubmittedtopreoperative

oculisticevaluationandallweresubmittedtoseriated

postopera-tiveoculisticcontrolintheimmediatepostoperativeperiod,after

3,6and12months.Allpresentedseverebitemporal

hemianop-sia;moreover,allpatientspresentedvisualacuityimpairment;in

particular,in2and1patientsrespectivelyofgroup1andgroup

2,suddenunilateralamaurosisoccurredbecauseofhaemorrhagic

presentationsoftheadenoma,andtheyweretreatedbyemergency

operations.Forthesamereasoninanotherpatientofgroup2an

acutebilateralamaurosisoccurredandhewasurgentlyoperated;

inthesefourpatientspreoperativestrumentaloculisticevaluation

wasnotperformed.

2.2. Surgicaltechnique

Thesupine positionwasusedin allpatients[3].In 21 (9of

group1and12ofgroup2)themicrosurgicalapproachwas endo-scopeassisted.Themicrosurgicalendonasalsubmucosalapproach throughonenostrilwasthesameforpatientsofbothgroupsuntil theexpositionoftheperitumoralduramater.Atthispoint,aswe observedin13(32.5%)patientsofgroupone,inthesevoluminous tumours,ifsurgicalremovalstartsfromthecentralpartofthe ade-noma,thesuprasellarcisternalplanecanprecociouslydescendinto thesellaturcica,compressingportionsofthetumourtowardsthe lateralsidesoftheoperativeﬁeld(Fig.1A);therefore,thesepartsof tumourbecomedifﬁculttoremove,alsowiththeaidofthe endo-scope;inthiseventualityitisfrequenttheoccurrenceofdamaging thesuprasellarcisternal plane(intraoperativeCSF leak)andthe relatedpossiblecomplicationsasstretchoftheopticchiasmand postoperativerhinoliquorrhea.

Themodiﬁedtechniqueforthesevoluminousadenomas con-sisted in opening at the beginning only the lateral parts of peritumoralduramater(Fig.1B).Inthisway,thecentralpartof theduramaterremainsinsupportofthecentralpartoftumour andsuprasellarcisternalplane.Afterremovaloflateralpartsofthe tumour,thecentralpartofperitumoralduramaterisopenedand thecentralintra-andsupra-sellarpartsofthetumourareremoved.

3. Results

3.1. Tumoralremovalandintraoperativeprecociousemptysella Whentumourspresentedcavernoussinusextension,our pre-operativepurposewastoperformagrosstotalremoval,leaving insituthecavernouscomponentwhichwassmall(lessthan1cm diam.max.) in all patients, avoiding the risksof damagingthe intracavernousvascular andnervous structures.In group1, we achievedtotal removalin18 patients(45%),grosstotalremoval (postoperative remnantless than 1cm max.diam.)in 12 (30%) (twoprecociousintraoperativeemptysella)and6(15%)(six pre-cociousintraoperativeemptysella)patientsinwhomcavernous sinuswasrespectivelyinﬁltratedornot;partialremoval (postop-erativeremnantmorethan2cmmax.diam.)wasaccomplishedin thelast4patients(10%)(intracavernous extensionin1patient)

inwhomprecociousintraoperativeemptysellaoccurred,avoiding theavailabilityofanextensiveremoval.

Ingroup2,totalremovalwasperformedin27(64%)patients, grosstotalremoval(postoperativeremnant lessthan1cmmax. diam.)in13(31%)and2(4.7%)patientsinwhomcavernoussinus wasrespectively inﬁltratedornot.Noprecociousintraoperative emptysellaoccurredinanypatientofthisgroup.

3.2. IntraoperativeandpostoperativeCSFﬁstula

Ingroup1intraoperativeCSFleakoccurredin9(22.5%)patients, andmeticulousreconstructionofthecranialbasewasnecessary. Althoughaccuracyofreconstructionofsellarpavement, postoper-ativerhinoliquorreaoccurredin3(7.5%)patients,associatedwith cephalalgiabecauseofpneumoencephalusinoneofthem.Inone patientpostoperativeCSFleakwassuccessfullytreatedbylumbar drainagemantainedfor4days;pneumoencephalusspontaneously resolvedafter5days.Inthe2otherpatients,instillationintothe sphenoidalsinusofhumanﬁbringlueunderCTcontrolwas suc-cessfullyperformed[4].

Ingroup2,intraoperativeCSFleakoccurredin1(2.4%)patient; nopostoperativerhinoliquorreawasobserved.

3.3. Managementofpostoperativetumoralremnantandtumoral recurrence

In group one,the 13 patientsin whomadenoma presented extensiontothecavernoussinus,weresubmittedtostereotactic radiotherapy;intheother9whopresentedatumoralremnant, asecondtranssphenoidalstage(becauseofpreviousonlypartial removal)followedbystereotactichypofractionatedradiotherapy was necessary in 3 patients, while in the other 6 stereotactic hypofractionatedradiotherapywasperformed.Notumoral recur-rencewasobservedduringanaveragefollow-upperiodof 11.2 years.Ingroup2,the13patientswithinvasionofcavernoussinus weresubmittedtostereotacticradiotherapywithoutevidenceof recurrenceafteranaveragefollow-upperiodof5.9years,whilein theother2 patientsonlyseriatedMRIs(oneatyear)were per-formed; there was no evidence of recurrence after an average follow-upperiodof4.6years.

3.4. Clinicaloutcome

Nonewneurologicaldeﬁcitwasobservedaftersurgeryinany patientofbothgroups.In31and27patientsofgroup1and2 respec-tively,transitorydiabetes; sinsipiduswas observedand treated withdesmopressin.

OutofthesevenpatientspresentingdiplopiabecauseofVI cra-nialnervepalsy,5presentedcompleterecoveryand2othermarked improvement.

Allpatientspresentedimprovementofthepreoperativedeﬁcit ofvisualacuityandvisualﬁeld,includedthe4patientsofgroup oneinwhompartialremovalwasperformed.

Regardingpituitaryfunction, allpatientspresented a preop-erativehypopituitarism;inonepatientofgrouponeandanother ofgroup2a reductionofblood levelsofcortisoloccurredafter anaverageperiodof9.5yearsaftersurgery.In3and2patientsof groups1and2respectively,reductionofbloodlevelsofcortisol

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Fig.1.(A)Drawingofpossibleprecociousintraoperativeemptyselladuringinadequatetranssphenoidalremovalofhugepituitaryadenomas:iftumourremovalstartswith theintra-andsuprasellarcentralpartsoftheadenoma,thesuprasellarcisternalplanecanprecociouslygodownintothesellaturcicaorevensphenoidalsinus,laterally compressingpartsofthetumour,whichshouldbedifﬁculttoberemoved.(B)Drawingofthesurgicaltechnique.Thelateralpartsofthetumourareinitiallyremoved(long blackarrows);thecentralpartofthetumouratthebeginningisleftinsituinsupportofthecisternalplane.

Fig.2.Caseofhugepituitaryadenomawithmarkedsuprasellarextensionoperatedonbytranssphenoidalapproach.Inthiscaseasmallsuprasellarremnantwasleftinsitu becauseitwasveryadherenttosuprasellarstructures.TherewasnooccurrenceofCSFleakduringsurgery,sothatnoparticularmaterialofappositionwasputinthe operativeﬁeld,remainingfreespaceunderthesuprasellarremnant.(A)PreoperativeT1sagittalpost-contrastMRI.(B)Postoperativepost-contrastMRIperformed5days aftersurgeryshowingasmallsuprasellarremnant.Itisnoticeableahypointensityareaunderthetumoralremnant(whitearrow)representingfreespaceunderthetumoral remnant.(C)Post-contrastMRIperformed1monthaftersurgery;aninitialdescentofthetumoralremnantisevidentandthereisyetanareaofhypointensityunderthe remnantitself(whitearrow).(D)Post-contrastMRIperformed2monthsaftersurgery:anulteriordescentintothesellarplaneofthetumoralremnantisevident,withtotal decompressionofsuprasellarstructures.

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4 M.F.Fraiolietal./ClinicalNeurologyandNeurosurgeryxxx (2012) xxx–xxx andfreetriiodothyronine(fT3)occurredafteranaveragefollow-up

periodof7.3yearsfromradiotherapy.Patientsarefollowedwith periodicalbloodhormonallevelscontrols.

Postoperativestayinhospitalwasdifferentbetweenpatients of the two groups: an average period of 8.2 and 4.3 days for patientsofgroups1and2respectively;thedifferencewasbecause of the presence of intraoperative and postoperative CSF leak whichrequired more time ofpostoperativeobservation. Out of the three patients of group one who presented postoperative rhinoliquorrea,cephalalgiaoccurredin1ofthembecauseof pneu-moencephalus which was evident at precocious postoperative MRI;patientsofgroup2presented nosigniﬁcantpostoperative discomfort.

Nasalpackingwasremovedintheﬁrstpostoperativedayinall patientsbut9ofgroup1and1ofgroup2,inwhomintraoperative CSFleakoccurred:itwasremoved6daysaftertheoperation.

4. Discussion

Thepresentedmodiﬁedsurgicaltechniqueisindicatedforhuge pituitaryadenomaswithmarkedsuprasellarextensionoperated onbytranssphenoidalsurgery.Thetechniqueallowstoprevent theoccurrenceofaprecociousintraoperativedescentofsuprasellar cisternalplaneanditsrelatedconsequencesabovementioned,and toperformatumourremovallargerthanpatientsoperatedwith standardtechnique.

WhenintraoperativeCSF leakoccurs,the surgeonhastoﬁll thesphenoidalsinusandthesellaturcicawithmaterialof appo-sition[5,6],andthissituationprecludes,orhoweverdelays,the progressivedescentintothesellaturcicaofthesuprasellartumoral remnant in case of gross total removal when the suprasellar tumoralremnantisadherenttosuprasellarstructures.Moreover, intraoperativeCSFleakexposespatientstotheriskofa postop-erativerhinoliquorreaanditsrelatedeventualcomplications[6] (cephalalgia,pneumoencephalus,subduralhaematoma, meningi-tis).

Onthecontrary,whenintraoperativeCSFleaksdoesnotoccur, aneventualtumoralremnantcandescendintothesellaturcica afterfewweeks(Fig.2)becauseoftheabsenceofexcessive pres-enceofmaterialofapposition.

Thetechniqueallowed,asaboveexplained,toachieveatumour removallargerthanstandardtechniqueinourpatients:evaluating attentlyourresults,excludingtumoursinﬁltratingcavernoussinus (13inbothgroups)inwhichourpreoperativeplanningwastodo notremovetheverysmallintracavernouscomponentperforming agrosstotalremoval,totalremovalintheothercaseswas66.6%in group1and93.1%ingroup2.

Evaluating each singular case, the tumoral remnant can be treatedby:observationbyseriatedMRIs,executionof asecond stagedtranssphenoidalapproach[7],executionofaradiotherapic treatment [8] (hypofractioned radiotherapy or one-shot radio-surgeryinourexperience).Moreover,tumourremovalislargerin patientsinwhomprecociousemptyselladidnotoccurredthan in patientsin whom it did, as we observed in our series: 64% and45%oftotalremovalingroup2andgrouponerespectively, withabsenceofpartialremovalingroup2.Finally,preservationof suprasellarcisternalplaneallowstoremovenasalpackinginthe ﬁrstpostoperativedayanddischargepatientsafter3–5daysfrom operation.

Notwithstanding the utility of the presented technique, we retainthathazardoustractions[9]onsuprasellarremnantswhich remain adherent to suprasellar structures and which do not descend into the sellar plane during the operation, should be avoided,becausevascularordiencephalicdamagescouldoccur, whileagrosstotalremovalinthesecases(Fig.2)assuresavery importantrecoveryofpreoperativevisualdeﬁcitsandallowsavery goodpostoperativequalityoflife.

Finally,regardingthetrigemino-cardiacreflexwhichcanoccur during transsphenoidal surgery or in generalduring skull base surgery[10,11]duetothestimulationofasensitivebranchofthe trigeminalnervewhilemanipulatingnearthecavernoussinus,we cansaythatinthepresentedpatients,duringsurgery,wedidnot observesohighandacuteheartrateandmeanarterialblood pres-surevariationstosuggestatrigemino-cardiacreflex.Itisexplicable becausewearenotuse,afterasignificantexperienceofcavernous sinussurgery[12],toovermanipulatetheeventualpara-or intra-cavernouscomponentofpituitaryadenomas,exceptforparticular casesinwhichthemaintumoralcomponentislocatedintothe cavernoussinusitself.

5. Conclusions

In our experience, the presented modiﬁed transsphenoidal microsurgicaltechniqueforremovalofhugepituitaryadenomas with marked suprasellar extension, minimizes damages tothe suprasellarcisternalplaneandthereforeintraoperativeCSF leak isveryrare;totalremovalcanbeachievedwithhigherpercentage ratethanpatientsoperatedwithstandardtechnique; postopera-tivestayinhospitalisshorterandnasalpackingcanberemovedin theﬁrstpostoperativeday.

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