Ci a ion: Felli, E.; Cinelli, L.;
Bannone, E.; Giannone, F.; Mu illo,
E.M.; Ba be io, M.; Kelle , D.S.;
Rod íguez-Luna, M.R.; Okamo o, N.;
Collins, T.; e al. Hype spec al
Imaging in Majo Hepa ec omies:
P elimina y Resul s om he
Ex-Machyna T ial. Cance s 2022,14,
5591. h ps://doi.o g/10.3390/
cance s14225591
Academic Edi o s: Massimo Rossi
and Ma eo Donadon
Recei ed: 3 Augus 2022
Accep ed: 12 No embe 2022
Published: 14 No embe 2022
Publishe ’s No e: MDPI s ays neu al
wi h ega d o ju isdic ional claims in
published maps and ins i u ional a il-
ia ions.
Copy igh : © 2022 by he au ho s.
Licensee MDPI, Basel, Swi ze land.
This a icle is an open access a icle
dis ibu ed unde he e ms and
condi ions o he C ea i e Commons
A ibu ion (CC BY) license (h ps://
c ea i ecommons.o g/licenses/by/
4.0/).
cance s
A icle
Hype spec al Imaging in Majo Hepa ec omies: P elimina y
Resul s om he Ex-Machyna T ial
Emanuele Felli 1,2,3,4 , Lo enzo Cinelli 3,5 , Elisa Bannone 3,6,7 , Fabio Giannone 1,2,3,4,
Edoa do Ma ia Mu illo 8, Manuel Ba be io 3,9 , Debo ah Susan Kelle 10 , Ma ía Ri a Rod íguez-Luna 3,11 ,
Na iaki Okamo o 3, Toby Collins 3, Alexand e Hos e le 3, Ca he ine Schus e 4, Didie Mu e 1,2,
Pa ick Pessaux 1,3,4, Jacques Ma escaux 3, Syl ain Gioux 11, E ic Felli 12,13 and Michele Diana 1,3,11,*
1Diges i e and Endoc ine Su ge y, Nou el Hopi al Ci il, Uni e si y o S asbou g, 67000 S asbou g, F ance
2Uni e si y Hospi al Ins i u e (IHU), Ins i u de Chi u gie Guidée pa l’image, Uni e si y o S asbou g,
67000 S asbou g, F ance
3Resea ch Ins i u e agains Diges i e Cance (IRCAD), 67000 S asbou g, F ance
4Ins i u o Vi al and Li e Disease, Inse m U1110, Uni e si y o S asbou g, 67000 S asbou g, F ance
5Depa men o Gas oin es inal Su ge y, San Ra aele Hospi al IRCCS, 20132 Milan, I aly
6Depa men o Su ge y, Is i u o Fondazione Poliambulanza, 25124 B escia, I aly
7Depa men o Panc ea ic Su ge y, Ve ona Uni e si y, 37134 Ve ona, I aly
8Dipa imen o di Scienze Medico Chi u giche e Medicina T aslazionale, Sapienza Uni e si àdi Roma,
00189 Roma, I aly
9Ospedale Ca dinale G. Panico, Gene al Su ge y Depa men , 73039 T icase, I aly
10 Lankenau Medical Cen e , Wynnewood, PA 19096, USA
11 ICube Labo a o y, Pho onics Ins umen a ion o Heal h, 67400 S asbou g, F ance
12 Depa men o Visce al Su ge y and Medicine, Inselspi al, Be n Uni e si y Hospi al, Uni e si y o Be n,
3012 Be n, Swi ze land
13 Depa men o BioMedical Resea ch, Hepa ology, Uni e si y o Be n, 3012 Be n, Swi ze land
*Co espondence: michele.diana@i cad.
Simple Summa y:
Majo hepa ic esec ions a e associa ed wi h highe isk o pos -ope a i e complica-
ions and pos -hepa ec omy li e ailu e. A e hepa ic pedicle clamping, ischemia- epe usion inju y
may some imes lead o pos -hepa ec omy li e ailu e. Ea ly de ec ion o , ideally, in a-ope a i e
p edic ion o li e dys unc ion o ailu e would be essen ial o imely ea men . Hype spec al
imaging (HSI) is a non-in asi e echnology ha de ec s he ela i e e lec ance o ligh a a wa eleng h
be ween 500 and 1000 nm, allowing he quan i ica ion o ele an o ganic compounds. This is he
i s clinical applica ion o HSI in a monocen ic majo hepa ec omy se ies, and he epo ed esul s
sugges ha HSI alues could be associa ed wi h sho - e m pos -ope a i e ou comes.
Abs ac :
Ischemia- epe usion inju y du ing majo hepa ic esec ions is associa ed wi h high a es o
pos -ope a i e complica ions and li e ailu e. Real- ime in a-ope a i e de ec ion o li e dys unc ion
could p o ide g ea insigh in o clinical ou comes. In he p esen s udy, we demons a e he in a-
ope a i e applica ion o a no el op ical echnology, hype spec al imaging (HSI), o p edic sho -
e m pos -ope a i e ou comes a e majo hepa ec omy. We conside ed i een consecu i e pa ien s
unde going majo hepa ic esec ion o malignan li e lesions om Janua y 2020 o June 2021. HSI
measu es included issue wa e index (TWI), o gan hemoglobin index (OHI), issue oxygena ion
(S O
2
%), and nea in a ed (NIR). P e-ope a i e, in a-ope a i e, and pos -ope a i e se um and
clinical ou comes we e collec ed. NIR alues we e highe in unheal hy li e issue (p= 0.003). S O
2
%
nega i ely co ela ed wi h pos -ope a i e se um ALT alues ( =
−
0.602), while
∆
S O
2
% posi i ely
co ela ed wi h ALP ( = 0.594). TWI signi ican ly co ela ed wi h pos -ope a i e ein e en ion and
OHI wi h pos -ope a i e sepsis and li e ailu e. In conclusion, he HSI imaging sys em is accu a e
and p ecise in ansla ing om p e-clinical o human s udies in his i s clinical ial. HSI indices a e
ela ed o se um and ou come me ics. Fu he expe imen al and clinical s udies a e necessa y o
de e mine clinical alue o his echnology.
Cance s 2022,14, 5591. h ps://doi.o g/10.3390/cance s14225591 h ps://www.mdpi.com/jou nal/cance s
Cance s 2022,14, 5591 2 o 13
Keywo ds:
hype spec al imaging; image-guided su ge y; hepa ec omy; majo hepa ec omy; pos -
hepa ec omy li e ailu e (PHLF)
1. In oduc ion
Li e cance and me as a ic li e disease a e a leading cause o cance mo ali y wo ld-
wide, accoun ing o mo e han 700,000 dea hs annually [
1
]. Indica ions o li e esec ions
ha e expanded wi h ad ances in su gical echniques and chemo he apy, allowing su -
geons o app oach lesions p e iously deemed un esec able [
2
,
3
]. Howe e , majo hepa ic
esec ions a e echnically challenging and associa ed wi h he highes isk o ad e se pos -
ope a i e ou comes [
4
,
5
]. Almos all majo hepa ec omies equi e pedicle clamping o
educe bleeding du ing li e ansec ion, which esul s in oxygen dep i a ion, he ca alys
o pa enchymal damage. This is u he compounded when blood low is ees ablished
om ischemia- epe usion inju y (IRI). IRI commonly esul s in pos -hepa ec omy li e
ailu e [
6
,
7
]; hus, p edic ing IRI o a oid pos -ope a i e li e dis unc ion is impo an .
Be o e su ge y, e alua ions wi h magne ic esonance imaging (MRI), compu ed omog a-
phy (CT) scan, o sequen ial hepa o-bilia y scin ig aphy can es ima e he olume o he
u u e li e emnan (FLR); adding an indocyanine g een (ICG) clea ance es can p o ide a
unc ional assessmen [
8
]. E en combined, hese modali ies p o ide a poo snapsho o
pos -ope a i e condi ions [
9
]. In he ope a ing oom, ICG luo escence imaging, mic odial-
ysis, ca bon dioxide senso s, and nea -in a ed spec oscopy (NIRS) can assess eal- ime
pe usion [
10
–
14
]. Howe e , hey a e limi ed by he need o exogenous dye, expensi e
comme cial equipmen , and lack o s anda diza ion in in e p e a ing esul s. On- able
ul asonog aphy (US) plays a c i ical ole in de ec ing inadequa e blood supply o ou low
obs uc ion bu is ope a o -dependen and canno p o ide a p ecise eal- ime map o li e
oxygena ion [
15
]. As a esul , cu en echnologies inaccu a ely es ima e pe usion o he
complica ion isk ollowing majo hepa ec omies. Thus, no el op ical imaging echnologies
ha could p o ide eal- ime in a-ope a i e eedback on oxygena ion and localiza ion o
ischemic damage a e needed.
Hype spec al imaging (HSI) is a non-in asi e echnology ha de ec s he ela i e
e lec ance o ligh a a wa eleng h be ween 500 and 1000 nm. The science was o iginally
de eloped o emo e sensing, hen success ully applied o mili a y, en i onmen al, geol-
ogy, ag icul u e, and global change esea ch, and la ely used o quan i ica ion o ele an
o ganic compounds [
16
,
17
]. Ou g oup ecen ly showed he po en ial bene i s o HSI as
an in a-ope a i e ool du ing image-guided su ge y in bowel and li e esec ions; HSI
was able o imp o e he su gical esec ion lines ia eal- ime o e lay o he hype spec al
image and ou ine ed-g een-blue (RGB) cap u es using augmen ed eali y (HYPER; hy-
pe spec al enhanced eali y) [
18
,
19
]. Fu he mo e, he quan i ica ion and disc imina ion
o di e en ypes o li e ischemia, including a e ial o o al ascula in low occlusion,
we e demons a ed o p o iding a li e iabili y sco e in a p e-clinical model o IRI [
20
,
21
].
Mo eo e , highe alues o wa e wi hin hepa ic issue could be ela ed o IRI and in lam-
ma ion [
22
,
23
]. Gi en hese p omising p elimina y p e-clinical esul s, he nex s ep o
alida ion was o ansla e he op ical imaging sys em in o he clinical se ing.
The goal o his wo k was o alida e a ela ionship be ween HSI pa ame e s and
pos -ope a i e ou comes a e majo hepa ec omy in human subjec s. The hypo hesis was
ha he imaging sys em would be sa e, accu a e, and p ecise in ansla ing om p e-clinical
o clinical li e esec ions.
2. Ma e ials and Me hods
2.1. S udy Design
The p esen s udy was pa o he EXMachyna3 p ojec (In aope a i e EXamina ion
Using MAChine-lea ning-based HYpe spec al o diagNosis & Au onomous Ana omy As-
sessmen , S asbou g, F ance), egis e ed a ClinicalT ials.go (NCT04589884) and app o ed
Cance s 2022,14, 5591 3 o 13
by he local e hics commi ee o he Facul y o Medicine o he Uni e si y o S asbou g
(ID-RCB: 2020-A01896-33). A single-ins i u ion, one-a m p ospec i e obse a ional s udy
was pe o med o his po ion o he s udy.
2.2. S udy Popula ion
Adul pa ien s unde going a majo hepa ic esec ion (4 o mo e segmen s) h ough
an open app oach be ween 1 Sep embe 2020 and 30 June 2021 o malignan hepa ic
lesions a Nou el Hôpi al Ci il (S asbou g, F ance), a e ia y u ban e e al cen e , we e
included. Pa ien s we e eligible i he li e lesions we e p ima y o me as a ic adenoca -
cinoma. Pa ien s we e excluded i unde 18 yea s o age, i he lesions we e benign, i
unde going a li e biopsy o smalle esec ion (less han 4 segmen s), hepa ic esec ion
h ough an app oach o he han open lapa o omy, o i he p ocedu e was abo ed p io o
he expe imen al po ion.
2.3. Su gical P ocedu e
The hepa ec omy ollowed a s anda d p o ocol. Two expe ienced hepa obilia y su -
geons pe o med all cases. In sho , a lapa o omy was made wi h a J-shaped Makuuchi
incision and ull explo a ion o he abdominal ca i y was pe o med o look o ca cino-
ma osis o o he pa hology. The li e was mobilized acco ding o he ype o hepa ec omy
pe s anda d o ca e. The hepa ic pedicle was enci cled wi h a loop o ascula con ol
and in e mi en clamping. In heal hy li e s, he hepa ic pedicle in e mi en clamping
was s anda dized as 20 min clamping ollowed by 10 min o . Whe eas o ci ho ic li -
e s, in e mi en clamping consis ed in 10 min o clamping ollowed by 10 min o [
24
].
In a-ope a i e ul asound was pe o med o con i m he su gical s a egy and o de ine
he ana omical landma ks be o e ansec ion. The po al ein and hepa ic a e y b anches
we e liga ed p io o hepa ec omy. Hepa ic ein liga ion was no ou inely pe o med. The
ansec ion line was sco ed wi h elec ocau e y once de ascula iza ion was comple ed.
Hepa ec omy was pe o med using he Ca i onic Ul asonic Su gical Aspi a o (CUSA,
In eg a Li esciences Co po a ion, Plainsbo o, NJ, USA). Hemos asis and bilios asis was
achie ed wi h 5-0 o 6-0 polyp opylene s i ches and Hem-o-lock clips. A inal ul asonog-
aphy was pe o med o ensu e hepa ic in low and ou low. Ex e nal bilia y d ainage
was le acco ding o he ype o hepa ec omy and su geon p e e ence; d ainage was no
sys ema ically used. The same s anda dized enhanced eco e y pa hway was used on all
pa ien s pos -ope a i ely [25].
2.4. Hype spec al Imaging (HSI)
The o e head ligh sou ces in he ope a ing oom we e swi ched o du ing HSI
acquisi ion. The HSI came a sys em (TIVITA, Diaspec i e Vision GmbH, Am Salzha ,
Ge many) acqui ed hype cube (640
×
480
×
100 each) and ou ine RGB images o en
de ined phases du ing he same acquisi ion mechanism. The HSI came a is equipped wi h
a pushb oom imaging spec ome e wi h a sli -shaped ape u e (mo ion ha occu s o
an HSI sys em o scan he ield o iew and acqui e spec al and spa ial in o ma ion), an
in e nal s eppe mo o con olling he sli o he spec og aph (de ice ha b eaks up a
single ull o a ion in o a numbe o much smalle pa - o a ions, mechanically connec ed
o a di ac ion g a ing o easily change he wa eleng h in he spec og aph), a high
pe o mance in a ed (IR)-enhanced complemen a y me al oxide semiconduc o (CMOS)
senso (elec onic chip ha con e s pho ons o elec ons o digi al p ocessing), and da a
p ocessing equipmen . Each hype cube was acqui ed in 6 s. The TIVITA hype spec al
came a was pe pendicula ly adjus ed o a 40 cm dis ance om he su gical su ace [
26
]. The
sys em illumina es he a ea o in e es wi h six halogen spo ligh s. The acquisi ion o a single
hype cube was pe o med wi h a came a-speci ic module o he Pe cep ion S udio so wa e
(Pe cep ion Pa k GmbH, G az, Aus ia). The spec al ange o his came a is
500–995 nm
.
The ligh sou ce pe spo is a 20 W OSRAM Halospo 70 Halogen lamp allowing o
in ense, b oadband, empe a u e-s able, homogeneous, and as pulses o adia ion. The
Cance s 2022,14, 5591 4 o 13
calib a ion o he wa eleng h was pe o med du ing came a p oduc ion. Da k cu en
e ec s we e co ec ed a e he eco ding o he da a cube by he dedica ed so wa e
componen . The came a collec s and p ocesses he in o ma ion om he elec omagne ic
spec um, measu ing he e lec ance spec a gene a ed by he a ge o s udy. To con e
image da a om adiance o ela i e e lec ance, a whi e e e ence objec wi h a high di use
e lec ance is used o c ea e a e e ence cube. The TIVITA
®
came a sys em has p ese
algo i hms, which can quan i y he ela i e oxygen sa u a ion (S O
2
%) o he supe icial
mic oci cula ion a a dep h up o 1 mm and he deepe laye s wi hin he nea -in a ed (NIR)
spec um wi h a pene a ion dep h o 4–6 mm. The issue wa e index (TWI) and he o gan
hemoglobin index (OHI) can be used o quan i a i ely assess and image he dis ibu ion
o wa e and hemoglobin, espec i ely, in he obse ed egion o in e es (ROI) [
27
]. The
in a-ope a i e se ing o HSI and acqui ed images is shown in Figu e 1.
Cance s 2022, 14, 5591 5 o 14
Figu e 1. In a-ope a i e se ing o HSI and acqui ed images. Du ing he acquisi ion o da a, all he
ligh s o he ope a ing oom a e u ned o (A). The acquisi ion was pe o med a he beginning o
he su gical p ocedu e (B) and a e he li e esec ion, a he end o su ge y (C). The RGB (Red-
G een-Blue) images and S O2%, NIR, OHI, and TWI indexes a e epo ed.
2.5. Da a Collec ion
P e-ope a i e, in a-ope a i e, and pos -ope a i e da a we e collec ed in a
p ospec i ely main ained elec onic da abase. P e-ope a i e demog aphic da a included
gende , age, body mass index (BMI), como bidi ies o dyslipidemia, diabe es melli us
(DM), hype ension, p e-exis ing hepa opa hy, p e-ope a i e p ocedu es
(chemoemboliza ion, po al ein emboliza ion, and bilia y d ainage), neoadju an
chemo he apy, and Ame ican Socie y o Anes hesiologis s classi ica ion (ASA) [28].
Labo a o y alues o al bili ubin, aspa a e ansaminase (AST), alanine ansaminase
(ALT), gamma-glu amyl ans e ase (GGT), alkaline phospha ase (ALP), albumin,
hemoglobin, p o h ombin ime (PT), and in e na ional no malized a io (INR) we e
collec ed p e-ope a i ely and pos -ope a i ely on pos -ope a i e days (POD) 1, POD 2,
and POD 5. In a-ope a i e da a included ope a i e ime ( om skin incision o closu e),
in a-ope a i e blood loss, need o ans usion, numbe o esec ed segmen s, clamping/
P ingle maneu e (yes/no), o al du a ion o li e ischemia, and RGB and HSI images,
wi h hei quan i a i e pa ame e s. Image acquisi ion was done be o e any li e
manipula ion (baseline, T0) and a he end o hepa ic esec ion/ a e specimen emo al
(T1). The ROIs we e iden i ied by su geons and da a scien is s oge he and he p ocedu e
Figu e 1.
In a-ope a i e se ing o HSI and acqui ed images. Du ing he acquisi ion o da a, all he
ligh s o he ope a ing oom a e u ned o (
A
). The acquisi ion was pe o med a he beginning o he
su gical p ocedu e (
B
) and a e he li e esec ion, a he end o su ge y (
C
). The RGB (Red-G een-
Blue) images and S O2%, NIR, OHI, and TWI indexes a e epo ed.
Cance s 2022,14, 5591 5 o 13
2.5. Da a Collec ion
P e-ope a i e, in a-ope a i e, and pos -ope a i e da a we e collec ed in a p ospec-
i ely main ained elec onic da abase. P e-ope a i e demog aphic da a included gende ,
age, body mass index (BMI), como bidi ies o dyslipidemia, diabe es melli us (DM), hy-
pe ension, p e-exis ing hepa opa hy, p e-ope a i e p ocedu es (chemoemboliza ion, po -
al ein emboliza ion, and bilia y d ainage), neoadju an chemo he apy, and Ame ican
Socie y o Anes hesiologis s classi ica ion (ASA) [
28
]. Labo a o y alues o al bili ubin,
aspa a e ansaminase (AST), alanine ansaminase (ALT), gamma-glu amyl ans e ase
(GGT), alkaline phospha ase (ALP), albumin, hemoglobin, p o h ombin ime (PT), and
in e na ional no malized a io (INR) we e collec ed p e-ope a i ely and pos -ope a i ely
on pos -ope a i e days (POD) 1, POD 2, and POD 5. In a-ope a i e da a included ope a-
i e ime ( om skin incision o closu e), in a-ope a i e blood loss, need o ans usion,
numbe o esec ed segmen s, clamping/ P ingle maneu e (yes/no), o al du a ion o
li e ischemia, and RGB and HSI images, wi h hei quan i a i e pa ame e s. Image ac-
quisi ion was done be o e any li e manipula ion (baseline, T0) and a he end o hepa ic
esec ion/ a e specimen emo al (T1). The ROIs we e iden i ied by su geons and da a
scien is s oge he and he p ocedu e was s anda dized as ollows: s a ing om he las
pic u e (T1), he en i e su ace o he emaining un esec ed li e was conside ed as ROI-1;
ROI-0 was exac ly he same a ea on he li e su ace a he beginning o he ope a ion
(T0). S O
2
%, NIR, TWI, and OHI alues we e eco ded o he same ROIs a T0 and T1.
Pos -ope a i e complica ions we e eco ded as majo (Cla ien-Dindo Class 3–5) and mino
(Cla ien-Dindo Class 1 and 2). His ologic da a on s ea osis, ib osis, and ci hosis om he
inal pa hological epo we e collec ed.
2.6. Ou come Va iables
The main ou come measu e was o assess a ela ionship be ween he HSI measu es,
se um ma ke s, and sho - e m pos -ope a i e clinical ou comes. The absolu e alues o
S O
2
%, NIR, TWI, and OHI alues we e analyzed a T0 and T1. Following his, no malized
alues ob ained ia sub ac ion o T1 and T0 measu emen s (
∆
) we e used o co ela e HSI
alues and su gical ou comes. Sho - e m ou come measu es analyzed included blood
loss, pos -hepa ec omy li e ailu e (PHLF), pos -hepa ec omy hemo hage (PHH), bile
leakage, and e-ope a ion (unplanned e u n o he ope a ing oom wi hin 60 days o he
index p ocedu e). These we e de ined and g aded pe he la es In e na ional S udy G oup
o Li e Su ge y (ISGLS) classi ica ions [
29
–
31
]. The p o h ombin ime (PT) < 50 and se um
bili ubin >50
µ
mol/L on POD 5 we e analyzed (“50–50 c i e ia”) as ma ke s o li e ailu e
and dea h a e majo hepa ec omy [32].
2.7. S a is ical Analysis
Ca ego ical da a we e exp essed as equency and pe cen ages. Con inuous a iables
we e desc ibed as medians, wi h in e qua ile ange (IQR), and compa ed using he S u-
den ’s - es o he Mann–Whi ney U- es , as app op ia e. No mali y o da a dis ibu ion
was assessed using his og am dis ibu ion isual inspec ion. Two- ailed p- alues we e
conside ed signi ican when alpha was less han 0.05. S a is ical analyses we e pe o med
using SPSS® o Windows, 28.0 (IBM Co po a ion, A monk, NY, USA).
2.8. E hical S a emen
In o med consen was ob ained om all subjec s in ol ed p io o pa icipa ion in
he s udy. This s udy was pa o he iEXMachyna3 p ojec (In aope a i e EXamina ion
Using MAChine-lea ning-based HYpe spec al o diagNosis & Au onomous Ana omy
Assessmen ), app o ed by he local e hics commi ee o he Facul y o Medicine o he
Uni e si y o S asbou g (ID-RCB: 2020-A01896-33). The s udy was designed in acco dance
wi h he Decla a ion o Helsinki and he ST eng hening he Repo ing o OBse a ional
s udies in Epidemiology s a emen (STROBE) guidelines [33].
Cance s 2022,14, 5591 6 o 13
3. Resul s
3.1. P eope a i e Va iables
Du ing he s udy pe iod, 15 pa ien s unde going majo hepa ec omies o malignan
li e umo s me inclusion c i e ia and we e included o expe imen al HSI analysis. The
mos equen p e-ope a i e diagnosis was hepa ocellula ca cinoma (HCC, 40%), ollowed
by colo ec al cance li e me as asis (CRLM, 33%). Fi e pa ien s unde wen neoadju an
chemo he apy, and one pa ien had bilia y d ainage o p e-ope a i e obs uc i e jaundice.
Full demog aphic de ails and biochemical assessmen a e epo ed in Table 1.
Table 1. Desc ip i e analysis o p e-ope a i e a iables.
Va iable To al Coho
n= 15
Gende , male (%) 10 (67)
Age, yea s * 69 (49; 73)
BMI, kg/m2*28.8 (26.6; 30.1)
BMI, >30 (%) 3 (20)
ASA, ≥3 (%) 9 (60)
Dislypidemia (%) 5 (33)
Diabe es (%) 6 (40)
Hype ension (%) 5 (33)
Hepa i is (HBV o HCV) (%) 2 (13.5)
Hepa ocellula ca cinoma (%) 6 (40)
Colo ec al me as asis (%) 5 (33)
Colangioca cinoma (%) 2 (13.5)
O he (%) 2 (13.5)
O e all como bidi ies (%) 11 (73.3)
Neoadju an he apy (%) 5 (33)
P e-ope a i e chemoemboliza ion (%) 5 (33)
P e-ope a i e po al ein emboliza ion (%) 6 (40)
P e-ope a i e bilia y d ainage (%) 1 (6.7)
P e-ope a i e bili ubin, µmol/L * 9.4 (5.7; 10.7)
P e-ope a i e se um AST, U/L * 29 (23; 63)
P e-ope a i e se um ALT, U/L * 46 (21; 60)
P e-ope a i e se um ALP, U/L * 103 (73; 174)
P e-ope a i e se um GGT, U/L * 86 (47; 172)
P e-ope a i e se um Hemoglobin, g/dL* 12.8 (11.3; 13.6)
P e-ope a i e se um PT, sec * 87 (75; 100)
P e-ope a i e se um INR * 1.1 (1; 1.21)
P e-ope a i e se um Albumin, g/dL * 43 (41; 46)
* Exp essed as median (in e qua ile ange). BMI body mass index, ASA Ame ican Socie y o Anes hesiologis s,
AST ASpa a e ansaminase, ALT ALanine T ansaminase, ALP Alkaline Phospha ase, GGT Gamma-Glu amyl
T ans e ase, PT P o h ombin Time, INR In e na ional No malized Ra io.
3.2. In aope a i e and Pos ope a i e Ou comes
In a-ope a i ely, he median ope a i e ime was 382 min. A P ingle maneu e was
pe o med in 10 pa ien s (67%), wi h a median du a ion o ascula in e mi en clamping
o 53 min. Pos -ope a i ely, eigh pa ien s o al had complica ions (53.3%); i e o al we e
majo complica ions. Fou pa ien s (26.9%) had li e ailu e, wi h one equi ing in asi e
ea men (g ade C PHLF). Two pa ien s de eloped pos -ope a i e bile leak necessi a ing
pe cu aneous d ainage, one had acu e enal ailu e equi ing empo a y hemodialysis,
and he o he had an in a-abdominal abscess ha equi ed pe cu aneous d ainage. The
o e all mo ali y was 13.5% (n= 2). One died om aspi a ion pneumonia, sep ic shock
and mul io gan ailu e (POD 21). The o he om hemo hagic shock due o hepa ic a e y
up u e (POD 1). Full in a-ope a i e and pos -ope a i e de ails a e epo ed in Table 2.
Cance s 2022,14, 5591 7 o 13
Table 2. Desc ip i e analysis o in a-ope a i e and pos -ope a i e a iables.
Va iable To al Coho
n= 15
Numbe o esec ed hepa ic segmen s * 5 (4; 6)
Du a ion o su ge y, minu es * 382 (324; 452)
Vascula clamping (%) 10 (67)
To al ime o ascula clamping, minu es * 53 (38; 80)
In a-ope a i e blood loss, mL * 490 (200; 650)
In a-ope a i e ans usion (%) 2 (13.5)
Pos -ope a i e complica ions, (Dindo–Cla ien) ≥3 (%) 6 (40)
Pos -ope a i e 90 days mo ali y (%) 2 (13.5)
Li e ailu e (%) 4 (26.9)
G ade A (%) 1 (6.7)
G ade B (%) 2 (13.5)
G ade C (%) 1 (6.7)
PHH (%) 2 (13.5)
Bilia y leakage (%) 2 (13.5)
Sepsis (%) 5 (33)
30-days e-ope a ion (%) 2 (13.5)
POD 1 se um Bili ubin, µmol/L * 25.7 (16.4; 52.1)
POD 2 se um Bili ubin, µmol/L * 24.1 (11.1; 67.1)
POD 5 se um Bili ubin, µmol/L * 25.5 (10.4; 61.6)
POD 1 se um AST, U/L * 788 (438; 1440)
POD 2 se um AST, U/L * 608 (261; 1228)
POD 5 se um AST, U/L * 75 (36; 128)
POD 1 se um ALT, U/L* 541 (380; 1047)
POD 2 se um ALT, U/L* 531 (352; 1383)
POD 5 se um ALT, U/L * 171 (79; 323)
POD 1 se um ALP, U/L * 75 (53; 106)
POD 2 se um ALP, U/L * 87 (57; 117)
POD 5 se um ALP, U/L * 94 (62; 185)
POD 1 se um GGT, U/L * 97 (57; 126)
POD 2 se um GGT, U/L * 74 (34; 112)
POD 5 se um GGT, U/L * 75 (54; 300)
POD 1 se um PT, sec * 52 (42; 67)
POD 2 se um PT, sec * 49 (32; 64)
POD 5 se um PT, sec * 50 (35; 75)
POD5 se um Bili ubin > 50 µmol/L (%) 5 (33)
POD5 se um PT < 50 sec (%) 6 (40)
50–50 c i e ia (%) 2 (13.5)
* Exp essed as median (in e qua ile ange). POD pos -ope a i e day, CD Cla ien–Dindo, PHH pos -hepa ec omy
hemo hage, AST ASpa a e ansaminase, ALT ALanine T ansaminase, ALP Alkaline Phospha ase, GGT Gamma-
Glu amyl T ans e ase, PT P o h ombin Time.
3.3. Co ela ion be ween HSI and Pe iope a i e Va iables
The S O
2
% alues a e li e esec ion we e signi ican ly highe in pa ien s who
unde wen p e-ope a i e bilia y d ainage o jaundice (0.772 s. 0.491, p= 0.033) and
lowe in cases wi h unheal hy ( a y, ib o ic, o ci ho ic) li e (0.308 s. 0.545, p= 0.011).
Ci ho ic li e p esen ed highe nega i e
∆
S O
2
% alues when compa ed o heal hy li e
(−0.223 s. 0.068, p= 0.05).
Fo he co ela ion be ween HSI and ou come a iables, S O
2
% showed a signi ican
nega i e co ela ion wi h ALT alues on POD 5 ( =
−
0.602, p= 0.030), while
∆
S O
2
%
showed a posi i e co ela ion wi h ALP measu ed on POD 1 ( = 0.594, p= 0.032). NIR
measu emen a he end o ope a ion p esen ed highe alues in unheal hy as compa ed o
heal hy li e (0.249 s. 0.021, p= 0.003). This ela ionship was main ained when compa ing
ib o ic and heal hy li e (0.439 s. 0.155, p= 0.028). P e-ope a i e his o y o dyslipidemia
was associa ed wi h lowe alues o inal NIRS (0.072 s 0.296, p= 0.029). Final NIR alues
showed a nega i e co ela ion wi h ALT alues on POD 2 ( =
−
0.666, p= 0.013) and POD
Cance s 2022,14, 5591 8 o 13
5 ( =
−
0.696; p= 0.008), while in a-ope a i e blood loss was nega i ely co ela ed wi h
he ∆NIR ( =−0.629, p= 0.021).
TWI was he only HSI index co ela ed wi h he a e o pos -ope a i e ein e en-
ions. The wo pa ien s who p esen ed wi h bilia y leakage and subsequen e-ope a ions
showed signi ican ly lowe alues o inal TWI (0.133 s. 0.270, p= 0.038). P e-ope a i e
chemoemboliza ion showed signi ican co ela ion wi h highe inal alues o TWI and
∆
TWI (p= 0.027 and p= 0.036, espec i ely). A nega i e co ela ion was ound be ween
∆TWI and PT measu ed on POD 1 ( =−0.567, p= 0.043).
Lowe OHI inal alues we e signi ican ly co ela ed wi h pos -ope a i e sepsis (0.641
s. 0.705, p= 0.045), while
∆
OHI was co ela ed wi h p e-ope a i e hype ension (
−
0.125
s.
−
0.019, p= 0.013) and PHLF (
−
0.075 s 0.023, p= 0.010), as well as a nega i e co ela ion
wi h ALT alues on POD 5 ( =
−
0.813, p= 0.001). Full de ails on he ela ionships be ween
HSI and pe i-ope a i e ou comes a e epo ed in Tables 3and 4and Tables S1–S4.
Table 3. Compa isons be ween inal hype spec al indexes and di e en pe i-ope a i e ea u es.
TWI Final pOHI Final pS O2Final pNIR Final p
P e-
ope a i e
Chemoemboliza ion
No
0.218 ±0.098
0.027
0.663 ±0.052 0.085 0.513 ±0.154 0.930 0.276 ±0.229 0.364
Yes
0.307 ±0.013 0.728 ±0.078 0.506 ±0.091 0.106 ±0.095
Bilia y d ainage
No
0.244 ±0.090
0.421
0.693 ±0.065 0.169 0.491 ±0.112 0.033 0.217 ±0.213 1.000
Yes*
0.322 0.594 0.772 0.200
Dislypidemia
No
0.240 ±0.103
0.583
0.673 ±0.062 0.350 0.528 ±0.155 0.537 0.296 ±0.208 0.029
Yes
0.269 ±0.058 0.710 ±0.078 0.480 ±0.078 0.072 ±0.101
Hype ension
No
0.191 ±0.074
0.060
0.677 ±0.050 0.727 0.474 ±0.165 0.455 0.251 ±0.274 0.797
Yes
0.283 ±0.081 0.691 ±0.078 0.531 ±0.114 0.196 ±0.172
In a-
ope a i e
Heal hy li e
Yes
0.265 ±0.076
0.814
0.657 ±0.026 0.531 0.545 ±0.102 0.011 0.021 ±0.006 0.003
No
0.248 ±0.093 0.691 ±0.072 0.308 ±0.118 0.249 ±0.204
Blood loss † 0.357
0.211
0.365 0.199 −0.100 0.735 −0.024 0.934
Pos -
ope a i e
Li e ailu e
No
0.247 ±0.074
0.768
0.681 ±0.070 0.566 0.517 ±0.140 0.738 0.198 ±0.207 0.368
Yes
0.262 ±0.153 0.707 ±0.067 0.487 ±0.110 0.282 ±0.225
Li e hemo hage
No
0.270 ±0.077
0.038
0.690 ±0.073 0.664 0.513 ±0.134 0.884 0.214 ±0.203 0.923
Yes
0.133 ±0.061 0.666 ±0.005 0.498 ±0.156 0.228 ±0.306
Bile leak
No
0.270 ±0.077
0.038
0.690 ±0.073 0.664 0.513 ±0.134 0.884 0.214 ±0.203 0.923
Yes
0.133 ±0.061 0.666 ±0.005 0.498 ±0.156 0.228 ±0.306
Sepsis
No
0.270 ±0.082
0.190
0.705 ±0.071 0.045 0.516 ±0.074 0.826 0.235 ±0.213 0.635
Yes
0.200 ±0.096 0.641 ±0.034 0.498 ±0.240 0.168 ±0.204
Re-ope a ion
No
0.270 ±0.077
0.038
0.690 ±0.073 0.664 0.513 ±0.134 0.884 0.214 ±0.203 0.923
Yes
0.133 ±0.061 0.666 ±0.005 0.498 ±0.156 0.228 ±0.306
ALP POD1 † −0.200
0.492
0.007 0.982 0.443 0.113 0.137 0.642
PT POD1 † −0.150
0.609
0.253 0.382 −0.026 0.929 0.011 0.970
ALT POD2 † −0.325
0.279
−0.127 0.680 −0.517 0.070 −0.666 0.013
ALT POD5 † −0.191
0.531
−0.004 0.989 −0.602 0.030 −0.696 0.008
* only 1 case in he p esen popula ion.
†
Spea man’s ank co ela ion coe icien . POD pos -ope a i e day, ALP
Alkaline Phospha ase, PT P o h ombin Time, ALT ALanine T ansaminase.
Cance s 2022,14, 5591 9 o 13
Table 4.
Compa isons be ween di e en ial alues o hype spec al indexes and di e en pe i-
ope a i e ea u es.
∆TWI p∆OHI p∆S O2p∆NIR p
P e-
ope a i e
Chemoemboliza ion No −0.049 ±0.077 0.036 −0.064 ±0.083 0.798 0.024 ±0.174 0.545 −0.001 ±0.241 0.435
Yes 0.059 ±0.083 −0.052 ±0.082 0.078 ±0.092 −0.088 ±0.109
Bilia y d ainage No −0.016 ±0.093 0.280 −0.060 ±0.083 0.966 0.024 ±0.130 0.067 −0.054 ±0.195 0.368
Yes * 0.093 −0.056 0.299 0.199
Dislypidemia No −0.001 ±0.119 0.773 −0.071 ±0.070 0.527 0.037 ±0.168 0.820 −0.039 ±0.250 0.943
Yes −0.018 ±0.039 −0.041 ±0.098 0.057 ±0.119 −0.027 ±0.099
Hype ension No −0.032 ±0.092 0.484 −0.125 ±0.057 0.013 0.075 ±0.150 0.579 −0.052 ±0.266 0.943
Yes 0.007 ±0.098 −0.019 ±0.064 0.026 ±0.150 −0.024 ±0.165
In aope a i e Heal hy li e Yes 0.065 ±0.092 0.063 −0.036 ±0.035 0.879 0.037 ±0.225 0.841 −0.177 ±0.165 0.064
No −0.013 ±0.078 −0.030 ±0.091 0.022 ±0.123 −0.032 ±0.146
Blood loss † 0.222 0.467 0.507 0.077 −0.427 0.146 −0.629 0.021
Pos -
ope a i e
Li e ailu e No −0.020 ±0.077 0.263 −0.075 ±0.077 0.010 0.069 ±0.133 0.171 −0.004 ±0.201 0.154
Yes 0.063 ±0.186 0.023 ±0.022 −0.087 ±0.191 −0.202 ±0.067
Li e hemo hage No −0.006 ±0.098 0.861 −0.048 ±0.072 0.090 0.029 ±0.141 0.203 −0.038 ±0.207 1.000
Yes * −0.024 −0.189 0.228 0.011
Bile leak No −0.006 ±0.098 0.861 −0.048 ±0.072 0.090 0.029 ±0.141 0.203 −0.038 ±0.207 1.000
Yes * −0.024 −0.189 0.228 0.011
Sepsis No −0.018 ±0.102 0.474 −0.045 ±0.079 0.246 0.019 ±0.115 0.257 −0.022 ±0.167 1.000
Yes 0.028 ±0.060 −0.108 ±0.071 0.132 ±0.231 −0.077 ±0.329
Re-ope a ion No −0.006 ±0.098 0.861 −0.048 ±0.072 0.090 0.029 ±0.141 0.203 −0.038 ±0.207 1.000
Yes * −0.024 −0.189 0.228 0.011
ALP POD1 † 0.146 0.635 −0.239 0.431 0.594 0.032 0.160 0.603
PT POD1 † −0.567 0.043 0.110 0.720 −0.234 0.442 0.267 0.378
ALT POD2 † 0.266 0.404 0.140 0.665 0.049 0.880 −0.154 0.633
ALT POD5 † −0.105 −0.745 −0.813 0.001 −0.091 0.778 −0.312 0.324
* only 1 case in he p esen popula ion.
†
Spea man’s ank co ela ion coe icien . POD pos -ope a i e day, ALP
Alkaline Phospha ase, PT P o h ombin Time, ALT ALanine T ansaminase.
4. Discussion
The p esen esul s demons a e he sa e y and easibili y o hype spec al imaging
in majo hepa ec omy, he abili y o HSI o p ecisely and accu a ely localize ischemic
damage du ing su ge y, and he ela ionship o HSI measu es o clinical ou comes and
se um ma ke s a e his high- isk p ocedu e. F om his i s human clinical applica ion
in hepa ec omy, esul s sugges ha HSI is a p omising ool which could po en ially help
ansla e in a-ope a i e ad anced ision o imp o e sho - e m pos -ope a i e ou comes.
Published wo k has demons a ed he bene i s o in a-ope a i e e alua ion o he
li e pa enchyma. Cu en ly, e alua ion o he emnan li e mainly elies on subjec i e
and ope a o -dependen me hods, naked-eye es ima ion, o ul asound e alua ion. This
subjec i e e alua ion becomes mo e challenging when unde lying li e disease is p esen .
The need o an objec i e, p ecise, and con enien analysis ool has d i en esea che s
o ind al e na i e solu ions. ICG- luo escence imaging is he mos common objec i e
me hod used o iden i y segmen al bounda ies o he li e , o mo e accu a e ana omic
esec ions [
34
,
35
]. Se e al wo ks epo ed he bene i o ICG as a p edic i e ac o o
PHLF [
6
,
36
,
37
]. Howe e , hese s udies we e biased by high he e ogenei y o he included
popula ion and hei e ospec i e design. In addi ion, he ICG exc e ion a e is a ec ed by
he unc ional exc e ion abili y o hepa ocy es, hepa ic blood low, shun olume, and bile
low a e, all which a e un eliable in li e dys unc ion [38].
HSI has g ea po en ial o o e come hese limi a ions. Ou g oup has p e iously used
HSI o assess S O
2
% and in a-ope a i ely localize p eselec ed ROIs du ing esophagec-
omy [
39
], small bowel ischemia [
40
], and hepa ec omy [
18
]. When adding an augmen ed
