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ORIGINAL ARTICLE
Surgery for liver metastases originatingfrom sarcoma—case series
Maximilian Zacherl & Gerwin A. Bernhardt & Johannes Zacherl & Gerald Gruber &
Peter Kornprat & Heinz Bacher & Hans-Jörg Mischinger & Reinhard Windhager &
Raimund Jakesz & Thomas Grünberger
Received: 6 March 2011 /Accepted: 22 June 2011 /Published online: 8 July 2011# Springer-Verlag 2011
AbstractIntroduction Liver metastases originating from varioustypes of sarcoma are a rare reason for hepatic resection.So far, even multicentre studies do hardly providestatistically relevant sample sizes. Thus, review ofavailable data can provide surgeons with useful infor-mation in similar cases. Therefore, this study can beregarded more as a contribution to this pool of datathan as a stand-alone paper.Patients and methods The study includes 10 women andfive men who underwent subtotal hepatic resection forsolitary (n=4) and multiple (n=11) liver metastasesoriginating from sarcoma. The median tumour diameterwas 60 mm (range 20–200 mm).Results Morbidity was 33%. One patient died within30 days after surgery. Resection was complete (R0) in67%. Median overall survival was 33.6 months, 5-yearsurvival 27%. The use of Pringle manoeuvre was signifi-
cantly associated with poorer outcome (p=0.014) andshorter period of recurrence-free survival (p=0.012).Diameter of liver lesion over 50 mm showed significantlyshorter recurrence-free survival (p=0.042).Conclusion Hepatic resection may be beneficial in patientswith isolated sarcoma metastasis in the liver.
Keywords Liver. Metastasis . Sarcoma . Hepatectomy
Introduction
Isolated liver metastases from different types of sarcoma arerare and remarkably limit survival [1]. Little is known abouthow resection of liver metastases originating from sarcomainfluences survival, though resection of pulmonary metas-tases from soft tissue sarcoma significantly benefits survival[2, 3]. Chemotherapy, commonly with doxorubicin, ifosfa-mide and dacarbazine, is the treatment of choice for patientswith locally advanced inoperable or metastatic disease [4].Liver metastases from sarcoma except for gastrointestinalstroma tumours (GIST), however, rarely respond to cyto-static chemotherapy and median survival seldom exceeds1 year [1]. Hepatectomy for primary liver tumours ormetastases from colorectal adenocarcinoma, renal adeno-carcinoma, Wilms’ tumour, testicular cancer and neuroen-docrine tumours is widely accepted. Data on outcome ofhepatic resection for metastatic sarcoma are rare andcontradictory. Reported 5-year survival rates range from 0to 83% after total hepatic resection [5–9]. Some authorshave reported long-term survivors of 10 years or more [8,10]. Hepatic resection has become increasingly reliable inrecent years with specialised centres reporting mortalityrates of less than 5% [8, 11, 12]. Thus, the indication forhepatic resection has been extended to cover non-colorectal
J. Zacherl : R. Jakesz : T. GrünbergerDivision of General Surgery, Department of Surgery,Medical University of Vienna,Vienna, Austria
M. Zacherl (*) :G. GruberDepartment of Orthopedics, Medical University of Graz,Auenbruggerplatz 6,8036 Graz, Austriae-mail: [email protected]
G. A. Bernhardt : P. Kornprat :H. Bacher :H.-J. MischingerDivision of General Surgery, Department of Surgery,Medical University of Graz,Graz, Austria
R. WindhagerDepartment of Orthopedics, Medical University of Vienna,Vienna, Austria
Langenbecks Arch Surg (2011) 396:1083–1091DOI 10.1007/s00423-011-0821-8
liver metastases [12, 13]. The largest series (n=56 and 158,respectively) have reported favourable outcome afterhepatectomy for metastatic sarcoma with a median survivalof around 40 months [14, 15]. These reports led us to re-evaluate patients who had undergone surgery for hepaticsarcoma involvement at our institutions, focusing onparameters that could influence patients’ survival (Fig. 1).
Patients and methods
This retrospective analysis is based on data gatheredbetween 1987 and 2006 from two tertiary referral centres.Fifteen patients who had undergone hepatic resection formetastases of soft tissue sarcoma of any origin wereincluded. Primary hepatic sarcoma or extra-hepatic sarcomadirectly invading the liver was excluded. Inclusion criteriafor hepatectomy were suitable general health status, andsingle or multiple liver metastases eligible for resectionwith respect to the liver segments involved. Data collectedincluded the type of sarcoma, histopathological pattern ofthe primary tumour and metastases, time of metastaticmanifestation, timing and type of hepatic resection, intervalbetween primary operation and hepatectomy, perioperativeparameters as operation time, blood transfusion, complica-tions during and after surgery, duration of intensive care andhospitalisation, histological status of resection margins,adjuvant or supplemental treatment and overall survivalafter liver surgery. Operative death was defined as occurringwithin the first 2 days after surgery and hospital death asoccurring from then until discharge. Recurrence wasdefined as any relapse of tumour either local or distantverified by histological examination, MRI or CT-scan.Morbidity included any complication, either surgical or
non-surgical, and was rated according to Clavien’s classi-fication with five severity grades and a focus on therapyused to correct a specific complication [16]. Patients werefollowed until July 1, 2009 or death. One patient was lost tofollow-up 41 months after metastasectomy.
Statistical analyses were performed with SPSS statisticalsoftware (Chicago, IL, USA) using the chi-square test,Mann–Whitney U test and Kruskal–Wallis test whereappropriate. Non-parametric data are shown as medianand range; parametrically distributed data are presented asmean and standard deviation. Statistical significance wasdefined as p <0.05.
Results
Fifteen patients met the inclusion criteria; their mean age atthe time of hepatectomy was 62±12 years. The male-to-female ratio was 1:3. The most frequent histological type ofliver metastasis was leiomyosarcoma (60%, n=9) (Table 1).Ten patients presented with metachronous liver involvementwith a median interval of 33 months (range 15–124 months); two had synchronous diagnosis of primarylesion and liver metastasis and three had metastatic liverdisease with unknown primary tumour. The primary tumourwas located in the small intestine in four; in the bones inthree; and in the pancreas, stomach, kidney, uterus andretroperitoneum in one patient each. Four patients receivedadjuvant chemotherapy, one patient was treated with localhyperthermia after liver surgery and one patient with GISTreceived imatinib mesylate (Glivec®, Novartis Pharmaceut-icals Corporation, marketed in the USA as Gleevec®). Themedian disease-free interval in patients with metachronousliver involvement (n=10) was 33 months (range 15–124 months). In seven patients, a single liver lobe wasinvolved; the remaining eight patients had bilobar involve-ment. Five patients had solitary liver metastasis. Themedian tumour diameter measured 60 mm (range 20–200 mm). In nine patients, the maximum diameter ofmetastasis exceeded 50 mm.
Surgery
Due to the long period under investigation, surgicaltechniques varied substantially. Hepatectomies were per-formed with clamp-crush digitoclasia technique until theCavitron Ultrasonic Surgical Aspirator (CUSA®) andLigaSure® instrument were introduced in the mid-1990s.The Pringle manoeuvre, a temporary occlusion of the portaltriad during resection to reduce intraoperative blood loss,was performed in nine patients with a median duration of32 min (range 10–60 min) [17]. A right hemihepatectomy
months12010896847260483624120
frac
tion
surv
ivin
g
1,0
,8
,6
,4
,2
0,0
Fig. 1 Overall survival after hepatectomy for sarcoma metastatic toliver (Kaplan–Meier estimation)
1084 Langenbecks Arch Surg (2011) 396:1083–1091
Table
1Clin
ical
parametersof
stud
ypo
pulatio
nat
thetim
eof
liver
surgery
No.
Age
(years)
Sex
Primary
lesion/histology
Hepatic
lesion
Presentation
Tim
einterval
(months)
Rstatus
Histology
ofliv
erparenchyma
Adjuvant
treatm
ent
Recurrence-free
survival
(months)
Postoperativ
esurvival
(months)
Com
orbidities
ASA
score
148
mPelvis/pleomorphic
sarcom
aaMultip
leMetachronous
160
Normal
None
57
St.p
.deep
venous
thrombosis(cavafilter
preop.),st.p.deep
infection
oftotalhiparthroplasty
1
277
fSmallbowel/leiomyosarcom
aSolitary
Metachronous
340
Normal
None
88
Stenosisof
carotid
artery,
st.p.radicalhysterectomy,
totalhiparthroplasty,st.p.
partialsm
allbowel
resection
2
358
mRib/chondrosarcom
aMultip
leMetachronous
291
n.k.
None
104
104
None
1
465
fDuodenum/leiomyosarcom
aMultip
leMetachronous
421
Steatosis
None
3333
Arterialhypertension
1
568
mDuodenum/GIST
Multip
leMetachronous
151
Steatosis
Taxotere
1534
St.p
.deep
venous
thrombosis,
sigm
oiddiverticulosis,
hiatus
hernia,adrenal
insufficiency,NID
DM,st.p.
TIA
,st.p.hemicolectomy
2
659
fPancreas/leiomyosarcom
aMultip
leSynchronous
00
Normal
None
21
St.p
.serial
ribfracture
and
fracture
ofsternum,st.p.
dilatatio
nandcurettage,
st.p.tonsillectomy,
depression
2
770
fUnknown/leiomyosarcom
aSolitary
Synchronous
00
Polycystic
None
6480
Peripheralarterial
disease,
cardiomyopathy,atrial
fibrillation,
st.p.
hyperthyroidism,st.p.
peritonitis,st.p.resection
ofadnexa
andsm
allbowel,
st.p.hysterectomy
2
869
mUnknown/leiomyosarcom
aMultip
leSynchronous
00
Normal
Holoxan,Etoposid
3141
St.p
.righthemicolectomy
1
963
fUnknown/malignschw
annoma
Solitary
Synchronous
00
Normal
None
3168
Cardiac
arrhythm
ia,pulm
onary
veno-occlusive
disease
1
1028
fGastric/m
alignGANT
Multip
leSynchronous
02
Normal
None
075
None
1
1175
mDuodenum/GIST
Multip
leMetachronous
160
Normal
Gliv
ec2
42St.p
.pancreaticoduodenectom
y2
1265
fUterus/leiomyosarcom
aSolitary
Metachronous
310
Steatosis
Taxotere,Gem
zar
1539
Arterialhypertension,
hyperlipidem
ia,st.p.
hysterectomy
3
1351
fRetroperitoneum
/leiomyosarcom
aSolitary
Metachronous
120
0Normal
None
00
St.p
.hemicolectomy
3
1458
fPelvis/leiomyosarcom
aMultip
leMetachronous
124
0Normal
None
712
Arterialhypertension,
cardiacarrhythm
ia,st.p.
hemipelvectom
y
3
1568
fKidney/leiomyosarcom
aMultip
leMetachronous
662
Steatosis
Hyperthermia
1832
Coronaryartery
disease,
st.p.
nephrectom
y3
GISTgastrointestinal
stromatumou
r,GANTgastrointestinal
autono
mic
nervetumou
r,st.p.status
post,NID
DM
non-insulin
-dependent
diabetes
mellitus,TIA
transientischem
icattack,ASA
American
Society
ofAnaesthesiologists
aFormerly
know
nas
malignant
fibrou
shistiocytoma
Langenbecks Arch Surg (2011) 396:1083–1091 1085
was performed in six cases with additional enucleation intwo patients and additional segmental resection in one. Lefthemihepatectomy with additional enucleation was per-formed in three cases. A bisegmentectomy was carried outin three cases with an additional wedge resection in two. Asingle segmentectomy was done in one and a single wedgeresection in three cases, with an additional enucleation inone of these patients. All resections were primary proce-dures with no previous liver surgery. The median durationof surgery (including the resection of the primary tumour intwo patients) was 220 min (range 120–525 min). Themedian perioperative volume of transfused packed redblood cells was 1,400 ml (range 0–6,300 ml). Unaffectedhepatic tissue was histologically classified as steatotic infour patients and normal in nine; in two cases, it was notclassified. Ten patients had a complete resection (R0); threeresected specimens showed positive margins upon histo-pathological evaluation (R1). Two patients had grossresidual tumour (R2). One patient with a macroscopictumour remnant at surgery had a huge primary malignantgastrointestinal autonomic nerve tumour (GANT) of thestomach with synchronous liver involvement.
Postoperative complications
The median duration of postoperative intensive care andhospitalisation, respectively, was 2 days (range 1–22 days)and 19 days (range 9–47 days). One death occurred in thehospital 22 days after right hemihepatectomy for metachro-nous metastases of a leiomyosarcoma originating from theretroperitoneum. This death was due to sepsis and follow-ing multiple organ failure (MOF), yielding a postoperativemortality rate of 7%. The complication rate was classifiedaccording to Clavien and revealed overall morbidity of 33%[16]. Five patients experienced one or more postoperativecomplications including pneumonia (n=1), cerebrovascularevent (n=1), bleeding requiring reoperation (n=1), localperitonitis (n=1), bile leakage (n=2), wound infection (n=2), renal failure (n=1), pancreatitis (n=1) and peritonitis(n=1). Interventional management of complications com-prised reoperation (one), percutaneous drainage (one) andtemporary endoscopic bile duct drainage (two). Threepatients suffered surgical complications equal to or greaterthan grade III, and three patients’ complications werebelow grade III.
Adjuvant therapy
Four patients were known to have had chemotherapy atsome point after liver surgery. One of each receivedTaxotere® (docetaxel), haloxane and etoposide phosphate,
and cisplatin under hyperthermia. One patient receivedchemotherapy in another hospital but provided no informa-tion on specific agents, and one patient with GISTand localrecurrence is still under treatment with Glivec®.
Survival
At the time of final follow-up, four patients (27%) survived10, 39, 42 and 104 months after hepatectomy. Three ofthem had evidence of hepatic (n=2) or distal recurrence.One patient had no evidence of disease 104 months aftermetachronous liver resection for multiple metastases from achondrosarcoma of the rib. Five patients died of disease-related causes (median survival 32 months) and two ofunrelated causes during follow-up without evidence ofdisease (median survival 17 months). The cause of death oftwo patients who had survived 116 and 136 months afterR0 hepatectomy could not be determined. One patient waslost to follow-up 41 months after surgery with evidence ofhepatic recurrence. The median overall survival was34 months (range 0–104 months). Current 3-year survivalis 47%; current 5-year survival is 27%. The sites of tumourrecurrences were the liver (n=6), lung (n=2), primarytumour site (n=1), skin (n=1) and bone (n=1). The medianoverall recurrence-free survival was 15 months (0–104 months). For overall survival prognosis, we excludedthe GIST patient who is still receiving Glivec®, and thepatient who died of postoperative complications. Forrecurrence-free survival prognosis, we excluded twopatients undergoing R2 resection as well as the patientwho died of postoperative complications.
Discussion
Almost one quarter of patients with sarcoma show liverinvolvement [1]. While liver metastases are rare in patientswith primary sarcoma of an extremity or the trunk,retroperitoneal and visceral abdominal sarcomas have aprevalence of liver metastasis of 16% and 62%, respectively[8]. To date, the majority of sarcomas metastatic to the liveror hepatic recurrences of same are generally treated withlocal or systemic chemotherapy, radiofrequency ablation(RFA) and/or portal vein embolisation [14, 18, 19]. Treat-ment options have been undergoing change since thedescription of mutations in growth factor receptor c-KIT(CD 117) and platelet-derived growth factor receptor-α(PDGFRα) responsible for tumour growth in GIST and itsinhibition by tyrosine kinase inhibitors such as imatinibmesylate (i.e. sti571, Glivec®). It has been shown thatsarcoma (including GIST in the ‘pre-Glivec®’ era) metastaticto the liver has a significant adverse predictive value for both
1086 Langenbecks Arch Surg (2011) 396:1083–1091
response to chemotherapy and survival [1, 8]. Livermetastases are apparently less chemosensitive than otherlesions [20], and the response of metastases from leiomyo-sarcoma is particularly poor [21].
Metastasectomy in contrast obviously prolongs survivalin selected patients with lung metastases originating fromsarcoma [2, 22].
Some authors have emphasised remarkable survival aftercomplete resection of sarcoma secondaries to the liver [5, 9,14, 15, 18, 23–25]. In a re-evaluation of the MemorialSloan Kettering Cancer Center series, median survival aftermicroscopically complete hepatic resection was 39 months[14]. Of the four patients in our study who had survivedhepatic surgery longer than 5 years, two had undergone R0resection. Three of them had more than one metastasis, withmaximum diameter of 90 to 200 mm. All patients withunknown primary tumour site survived longer than 3 years.
In concert with reports from other centres, one third ofour patients experienced postoperative complications. In aunivariate analysis, postoperative complication was asignificant predictor of shorter survival when we includedall patients (p=0.028) and showed a statistical trend afterexclusion of the patient with lethal outcome (p=0.057).Overall, the 90-day mortality rate after liver surgery fornon-colorectal metastasis is 4% in our hands, as reportedearlier [12]. Surgical mortality has declined from as muchas 20% in the 1970s and 1980s [10] to below 5% currentlyat specialised centres [14, 18].
Despite the comparatively high proportion of multiplemetastasis and bilobar manifestation, median overall sur-vival exceeded 33 months in our series. In 14 patients withcomplete follow-up of more than 5 years, survival was29%. This compares favourably with data for non-surgicalmanagement of sarcoma metastatic to the liver [1, 8].Pawlik and co-workers compared radiofrequency ablation(RFA) in a cohort of sarcoma liver metastases with andwithout liver resection with hepatectomy alone and found asignificant (p=0.002) negative influence of RFA in bothgroups compared to resection alone [18]. Mavligit and co-workers applied at least two chemo-embolisation proce-dures in 14 patients with liver metastasis originating fromleiomyosarcoma. They observed more than 50% tumourregression in 70% of patients with a median duration ofregression of 12 months, but there was only one 3-yearsurvivor [26].
While chemotherapy for sarcoma metastatic to the liveris rarely followed by remarkable regression, tyrosine kinaseinhibitor (TKI) showed sustained objective responses inmore than 50% of patients with GIST [27, 28]. DeMatteo etal. published a paper on TKI therapy after surgery formetastatic GIST including 17 out of 40 patients with partialliver resection and found a significant correlation of
survival in responders (n=20) with a preliminary 100% 2-year survival rate [29]. In our series, of two patients withGIST and local recurrence, one who is still receivingGlivec® postoperatively is alive 42 months after surgery.This raises the question of whether further studies shouldcompare sarcoma of other origin with GIST.
Largest diameter of metastatic lesion greater than 50 mmwas significantly associated with longer recurrence-freesurvival in a univariate analysis in our series. But it showedno statistical influence on overall survival. Local recurrencerate was higher in patients with lesions smaller than 50 mmafter complete resection. The only negative prognostic factorin our study associated with overall survival and recurrence-free survival was the Pringlemanoeuvre [17]. Patients operatedon with Pringle manoeuvre had a trend towards morepostoperative complications without showing statistical sig-nificance. The Pringle manoeuvre had no influence on thenumber of applied blood transfusions and the operation time.It is known that Pringle’s manoeuvre produces an ischemia–reperfusion injury in the short term [30]. However, since theintroduction of new blood-saving dissection devices, themanoeuvre has become less important. Unfortunately, ourdata lack conclusive comparable assessment of hepaticsteatosis because of inconsistent histological classification[31]. It remains unclear on the effect of the amount andcondition of residual liver parenchyma on outcome. Apostoperative complication showed a statistical trend regard-ing survival. Bias may be due to favouring poorer healthstatus. Nevertheless, these findings emphasise the role ofpatient selection in terms of comorbidities and the postoper-ative remnant of liver parenchyma. Only five out of 22reviewed papers with cohorts of at least six patientsundergoing liver surgery for metastatic sarcoma presentsignificant prognostic factors [5–9, 11, 14, 15, 18, 23–25,32–37] (see Tables 2 and 3). Two research groups mention atime span between surgery of the primary lesion andoccurrence of liver metastases of more than 2 years as asignificant prognostic factor [14, 25], and two other groupsfound complete resection (R0) significant for longer survival[5, 37]. Number and size of liver metastases and presence ofextrahepatic disease upon liver surgery were marginally non-significant prognostic factors according to multivariate anal-ysis of one of the largest series to date [14]. Two publishedstudies definitely revealed no significant prognostic factors [8,9] and the rest of the papers reviewed did not provide anyfurther information [6, 7, 11, 15, 23, 24, 32–36, 38].
Conclusion
We share the impression that number and intrahepaticdistribution of liver lesions appear to play a minor role
Langenbecks Arch Surg (2011) 396:1083–1091 1087
regarding outcome when complete resection with a sufficientfunctional liver remnant is possible. Size of liver lesions mayhave an impact on local and systemic recurrence rate. Inagreement with recent reports, we conclude that radical
surgery for isolated liver metastasis arising synchronously ormetachronously from sarcoma may have a survival benefit forpatients with liver metastasis only and whose physicalcondition does not preclude major surgery.
Table 2 Prognostic factors of study population
n Median survival, months (SD) p value n Median recurrence-free survival,months (SD)
p value
Resection margin 0.354 0.090R0 8 24.0 (2.0–79.6) 9 7.7 (2.0–64.1)
R1, 2 5 33.6 (31.3–103.7) 3a 25.2 (14.7–103.7)
Adjuvant systemic therapy 0.724 1.000Yes 4 36.1 (2.0–79.6) 4 7.7 (2.0–64.1)
No 8 21.0 (31.9–41.8) 7 14.7 (2.4–31.3)
No data 1 1
Postoperative complication 0.073 0.066Yes 5 8.2 (2.0–75.3) 3 5.2 (2.0–5.2)
No 6 53.1 (11.8–103.7) 7 22.9 (2.4–103.7)
No data 2 2
Type of resection 0.731 0.522Major 7 33.6 (2.0–79.6) 6 11.2 (2.0–64.1)
Minor 6 38.5 (11.8–103.7) 6 23.0 (2.4–103.7)
Largest diameter 0.165 0.042≥5 cm 6 71.5 (8.2–103.7) 5 31.3 (7.7–103.7)
<5 cm 6 32.6 (2.0–41.8) 7 6.6 (2.0–32.6)
No data 1 0
Number of metastases 0.503 0.497Single 4 53.1 (8.2–79.6) 8 22.9 (7.7–64.1)
Multiple 9 32.6 (2.0–103.7) 4 10.7 (2.0–103.7)
Operating time 0.329 0.071≥250 min 5 31.9 (2.0–75.3) 7 5.0 (2.0–15.0)
<250 min 6 41.0 (8.2–79.6) 3 14.6 (2.4–64.0)
No data 2 2
Resection of primary lesion 0.284 0.610Synchronous 5 67.6 (2.0–79.6) 8 31.2 (2.0–64.1)
Metachronous 8 32.6 (7.1–103.7) 4 11.3 (2.4–103.7)
Histology 0.284 0.705Leiomyosarcoma 8 32.2 (2.0–79.6) 7 14.6 (2.0–64.1)
Non-leiomyosarcoma 5 67.6 (7.1–103.7) 5 22.9 (5.2–103.7)
Pringle manoeuvre 0.014 0.012Yes 7 21.8 (2.0–41.8) 7 6.6 (2.0–31.3)
No 6 71.5 (32.6–103.7) 5 32.6 (14.7–103.7)
Primary lesion 0.112 0.115Known 10 32.6 (2.0–103.7) 9 8.0 (2.0–103.7)
Unknown 3 67.6 (41.0–79.6) 3 31.0 (31.0–64.0)
Hepatic distribution 0.366 0.423Unilobular 6 22.7 (2.0–79.6) 6 11.2 (2.0–64.1)
Bilobular 7 41.4 (7.1–103.7) 6 31.2 (2.4–103.7)
Steatosis 0.432 0.059Yes 5 33.6 (31.9–79.6) 4 23.7 (14.6–64.1)
No 7 26.4 (2.0–75.3) 7 6.6 (2.0–31.3)
No data 1 1
a Excluding two patients undergoing R2 resection
1088 Langenbecks Arch Surg (2011) 396:1083–1091
Table
3Literature
review
:hepatic
resectionforsarcom
ametastasis
Reference
nMedian
follo
w-up
(months)
Study
period
(years)
Age
ofstudy
populatio
n(years)
R0(%
)R1(%
)R2(%
)Recurrence-free
survival
(months)
Medianoverall
survival
(months)
3-Year
survival
5-year-
survival
Leiom
yosarcom
aPrimary
lesion
located
atextrem
ity
Primary
lesion
located
atviscera
Foster[38]
12ND
ND
ND
ND
ND
ND
ND
11ND
11%
100%
0%84%
Jaques
etal.[8]
14ND
5ND
83%
ND
7%ND
3030%
0%ND
ND
71%
Harrisonet
al.[34]
27ND
15ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
Eliaset
al.[6]
13ND
12ND
ND
ND
ND
ND
ND
62%
18%
ND
ND
ND
Chenet
al.[5]
1153
1157
55%
27%
18%
ND
3927%
ND
ND
0%45%
Hem
minget
al.[7]
7ND
20ND
ND
ND
ND
ND
ND
ND
29%
ND
ND
ND
Langet
al.[9]
26ND
1354
65%
13%
22%
ND
ND
40%
20%
100%
0%72%
vanRuthet
al.[36]
6ND
10ND
100%
0%0%
ND
2733%
ND
33%
17%
66%
DeM
atteoet
al.[14]
5658
1853
c75%
25%
0%16
3950%
30%
36%
9%68%
Goering
etal.[33]
14ND
10ND
ND
ND
ND
ND
ND
44%
ND
45%
14%
21%
Yedibela
etal.[37]
15ND
23ND
60%
ND
ND
ND
ND
ND
ND
100%
ND
ND
Ercolaniet
al.[23]
10ND
13ND
ND
ND
ND
ND
4464%
36%
ND
ND
ND
Paw
liket
al.[18]
5336
954
100%
0%0%
ND
4765%
27%
27%
0%53%
Adam
etal.[15]
158
ND
34ND
79%
12%
9%ND
4048%
39%
ND
ND
ND
Earle
etal.[32]
19ND
15ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
Teoet
al.[39]
728
647
100%
0%0%
ND
28ND
ND
57%
0%86%
Lendoireet
al.[35]
23ND
1757
83%
17%
0%ND
1918%
9%ND
ND
ND
Reddy
etal.[24]
31ND
ND
ND
ND
ND
ND
ND
38ND
ND
ND
ND
ND
O’Rourkeet
al.[11]
21ND
20ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
Rehders
etal.[25]
2784
10ND
78%
22%
0%67%
d44
ND
49%
30%
18%
52%
Owndata
1534
1965
67%
20%
13%
1534
47%
27%
70%
0%33%
Total
565
Mean
4915
5679%
14%
6%34
44%
25%
60%
6%59%
Reference
Primarylesion
locatedat
retroperito
neum
Other
locatio
nof
prim
ary
lesion
Interval
(months)
Metachronous
incidence
Solitary
liver
lesion
Major
complication
Operativ
emortality
30-D
aymortality
Anatomical
resection
PCT
adjuvant
PCT
neoadjuvant
Intra-arterial
chem
o/em
bolisation
Local
recurrence
rate
Lung
metastases
Significant
prognostic
factors
Foster[38]
8%8%
ND
ND
ND
0%0%
8%ND
ND
ND
0%7%
ND
ND
Jaques
etal.[8]
ND
ND
30ND
ND
ND
0%0%
71%
ND
ND
ND
79%
ND
Nosignificant
prognostic
factorsdetected
Harrisonet
al.[34]
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
Eliaset
al.[6]
ND
ND
ND
ND
ND
ND
ND
ND
54%
ND
ND
ND
ND
ND
ND
Chenet
al.[5]
42%
8%16
100%
0%ND
0%0%
8%27%
8%0%
ND
ND
Com
pleteresection
(R0)
p=0.03
Hem
minget
al.[7]
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
Langet
al.[9]
28%
0%ND
65%
35%
29%
e0%
6%30%
ND
ND
ND
ND
ND
Nosignificant
prognostic
factorsdetected
vanRuthet
al.[36]
17%
0%ND
ND
ND
ND
0%ND
ND
ND
ND
ND
ND
ND
ND
DeM
atteoet
al.[14]
14%
9%38
80%
20%
ND
0%0%
73%
41%
ND
20%
56%
18%
Tim
eto
liver
metastases
>2years
(p=0.002)
Goering
etal.[33]
7%58%
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
Langenbecks Arch Surg (2011) 396:1083–1091 1089
Table
3(con
tinued)
Reference
Primarylesion
locatedat
retroperito
neum
Other
locatio
nof
prim
ary
lesion
Interval
(months)
Metachronous
incidence
Solitary
liver
lesion
Major
complication
Operativ
emortality
30-D
aymortality
Anatomical
resection
PCT
adjuvant
PCT
neoadjuvant
Intra-arterial
chem
o/em
bolisation
Local
recurrence
rate
Lung
metastases
Significant
prognostic
factors
Yedibela
etal.[37]
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
Com
plete
resection(R0)
a
Ercolaniet
al.[23]
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
Paw
liket
al.[18]
33%
14%
ND
ND
ND
15%
0%0%
72%
79%
58%
7%50%
34%
Adjuvanttherapy
with
imatinib
mesylatein
GIST(p=0.03),
adjuvant
therapy
with
additio
nal
radiofrequency
ablatio
nor
RFA
alone(including
13patientswith
RFA
alone)
p=0.002
Adam
etal.[15]
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
25%
ND
ND
Earle
etal.[32]
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
Teoet
al.[39]
14%
0%11
57%
43%
0%0%
0%ND
29%
0%0%
43%
29%
ND
Lendoireet
al.[35]
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
61%
ND
ND
Reddy
etal.[24]
ND
ND
ND
ND
ND
ND
ND
ND
ND
52%
26%
ND
ND
ND
ND
O’Rourkeet
al.[11]
ND
ND
ND
ND
ND
ND
0%ND
ND
ND
ND
ND
ND
ND
ND
Rehders
etal.[25]
30%
0%44
85%
15%
18%
7%ND
70%
15%
0%0%
26%
26%
Tim
eto
liver
metastases
>2years
(p=0.0134),
repeat
liver
surgery
(p=0.0007)
Owndata
27%
40%
1670%
33%
20%
0%7%
80%
27%
0%0%
60%
13%
Pringle
manoeuvre
(p=0.013),
largestdiam
eter
ofmetastatic
lesion
(p=0.042)
b
Total
22%
14%
2676%
24%
11%
1%3%
57%
39%
15%
4%45%
24%
ND
nodata,GISTgastrointestinal
stromatumou
raOnlyforleiomyo
sarcom
abOnlyforrecurrence-freesurvival
cInclud
ing27
6patientswith
outliv
ersurgery
dTw
o-year
recurrence-freesurvival
eInclud
ingpatientsun
dergoing
second
andthirdliv
erresection
1090 Langenbecks Arch Surg (2011) 396:1083–1091
Acknowledgements The authors thank Rene Adam, M.D. andJavier C Lendoire, M.D. for their review of Table 3 and EugeniaLamont for proofreading the manuscript.
Conflicts of interest None.
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