Results of Surgery and Multimodal
Therapy for Patients with Soft Tissue Sarcoma Invading to Vascular Structures
Taken from: Cancer 1999;85:396-408.
© 1999 American Cancer Society.
Presented at the third annual
meeting of the Connective Tissue Oncology Society (CTOS),
Milan, Italy, November 6-8,
Hohenberger, M.D., Ph.D. 1
Jens R. Allenberg, M.D.,
Peter M. Schlag, M.D.,
Peter Reichardt, M.D.3
Address for reprints:
Peter Hohenberger, M.D.,
Robert-Rossle Hospital and
Medizinische Fakultat Charite,
The Humboldt University
Lindenberger Weg 80, D-13125
of Surgery and Surgical Oncology, Robert Rossle Hospital and Tumor Institute,
Humboldt University of Berlin,
of Vascular Surgery, Department of Surgery, University of Heidelberg, Heidelberg,
of Hematology, Oncology and Tumorimmunology, Robert Rossle Hospital and
Tumor Institute, Charite, Humboldt University of Berlin, Berlin, Germany.
BACKGROUND. The aim
of this study was to analyze the impact of resection and reconstruction
of major vessels on the limb salvage rate, local disease free survival,
and overall survival for patients with soft tissue sarcomas invading to
METHODS. Twenty patients
were treated in a 7-year period by one surgical team. Preoperative therapy
consisted of isolated limb perfusion (n = 6), systemic chemotherapy (n
= 4), systemic chemotherapy combined with regional hyperthermia (n = 2),
and external beam irradiation (n = 1). All patients underwent resection
of the sarcoma monobloc together with the neurovascular bundle invaded.
Vessels were replaced by an autologous vein transplant or an allograft,
and, in six patients, a myocutaneous flap or skin graft had to be used
for soft tissue coverage.
examination revealed negative histologic margins (RO-resection) and infiltration
of the neurovascular bundle in all patients. In four patients, a local
recurrence was observed, and, in three of them, reresection with negative
margins was achieved. The mean local recurrence free survival was 54 months
(confidence interval [CI],
42-66 months), and the mean overall survival was 48 months (CI, 32-57 months).
Limb salvage was achieved in 19 of 20 patients. Eleven patients developed
distant metastases after a mean survival time of 30 months.
sarcoma resection, including vessel replacement after preoperative multimodal
therapy, provides long term local control and limb salvage. Amputation
of extremity sarcoma can hardly be justified, even in cases of tumor invasion
to neurovascular bundles. However, efforts to achieve better control over
systemic spread are required for long term disease free survival. Cancer
1999;85:396-408. © 1999 American Cancer Society.
neurovascular invasion, multimodal therapy, resection, ves-
Soft tissue carcinoma (STS)
is a very uncommon disease accounting for less than 1% of all newly diagnosed
adult cancers in Europe and the United States annually.1
The preservation of the limb has become increasingly possible in lesions
affecting the extremities due to improved surgical skill and multimodality
surgery was found to result in equal survival but higher rates of local
recurrence than amputation.3,4
A recent analysis of prognostic
factors obtained from prospec-tively collected data on more than 1000 patients
revealed microscopically positive margins and recurrent disease at presentation
as significant independent adverse prognostic factors for local recurrence.5
For distant recurrence and disease specific survival, independent adverse
factors were deep location of the sarcoma and high grade.5,6
High grade sarcomas are
characterized by an increased rate of infiltration to neurovascular bundles
and a high rate of distant metastases.7.8
The attachment of tumors to major vascular structures with adequate margins
of clearance difficult to achieve has to be regarded as a major limitation
of effective surgical therapy. Previously, amputation had been the adequate
treatment, but the problem of systemic spread could not be solved by this
procedure either. Vessel-invasive tumors often present as recurrent disease,
resulting in positive margins after tumor resection. Both adverse prognostic
factors further contribute to the poor outcome.
To save the limb despite
the vessel-invasive tumors, limited resections combined with brachyther-apy
to the tumor bed have been applied successfully,9,10
However, as a sole surgical treatment, radical resection, including removal
of the vessels infiltrated by tumor, with consecutive reconstruction using
an allograft or an autologous vein bypass was inaugurated more than 15
Twenty patients underwent
extended soft tissue sarcoma resection, including vascular surgical reconstruction,
by one surgical team during a 7-year period. Preoperatively, the majority
of the patients were treated by combined modality therapy intended to down-stage
the tumor and facilitate resection. We analyzed the further course of our
patients with respect to limb-salvage rate, local disease free survival,
and overall survival.
PATIENTS AND METHODS
Twenty patients (14 males
and 6 females; median age, 47 years; range, 22- 65 years; see Table 1)
underwent resection of soft tissue sarcoma of the extremities with curative
intent, including vascular reconstructions of the arteries and/or veins
resected due to tumor infiltration of the neurovascular bundle. Five patients
were treated consecutively from 1989 to 1992 at the Department of Surgery,
University of Heidelberg. Subsequently, another 15 patients were operated
on at the Division of Surgery and Surgical Oncology, Robert-Rossle Hospital,
Humboldt University of Berlin.
Ten patients were treated
for the primary tumor, and five patients were referred to for recurrent
disease (patients 6, 9, 14, 15, and 18; see Table 2). Of these, three patients
had been treated previously by radiotherapy (54-78 grays [Gy]; patients
14, 15, and 18) and presented with an in-field recurrence. Another five
patients were referred for residual disease after an attempt to resect
the primary tumor (patients 1, 4, 5, 11, and 16). Fifteen tumors were located
Angiogram detected stenosis
of the artery in five patients, with subtotal occlusion in another patient.
The artery was displaced by the tumor in eight patients and was encased
in another patient (Fig. 1). Thrombosis or occlusion of a major vein in
close vicinity to the tumor was observed in seven patients. Three patients
showed stenosis, another patient showed direct invasion to the vein wall,
and, in two patients, the vein was displaced by the tumor.
Ten patients were treated
by surgical resection alone, and another ten patients underwent multimodal
treatment. Isolated hyperthermic limb perfusion (ILP) with rh tumor necrosis
factor a (rhTNFa) and melphalan12 was performed in five patients. Of these,
two patients had systemic chemotherapy13, 14
with a complete remission of lung metastases but only partial remission
of the primary tumor. Two patients (9 and 20) had systemic neoadjuvant
chemotherapy for their tumors combined with regional hyperthermia15 in
a third patient (18). Another patient (17) received preoperative radiotherapy
of 66 Gy. Another patient (13) underwent postoperative radiotherapy (64
Gy) combined with five cycles of doxorubicin plus ifosfamide participating
in a multicenter trial (CWS-E protocol; coordinator, W. Hartlapp, M.D.,
Osnabriick, Germany). All studies in which the patients participated were
approved by the local ethics committee of the Humboldt University of Berlin,
and the patients provided written informed consent.
The indication to resect
the vessels was due either to the angiographic findings, the location of
the sarcoma (e.g., Hunter's canal), or fixation of the tumor to the neurovascular
bundle. Infiltration to nerves was present in five patients (femoral or
tibial nerve), and the nerve had to be sacrificed totally or partly. In
another five patients, predominantly those with lipo-sarcomas, tumor growth
was adjacent to major nerves that could be salvaged by using the epineurium
as a dissection plane (epineurectomy). Intracompartmen-tal lesions were
resected by compartmental excision. In extracompartmental lesions, a "wide
-excision" that included the surrounding muscle group was performed. Vascular
resection was performed within the anatomical segments of the vessels as
far as possible from the point of infiltration by the sarcoma (Table 1).
Resection specimens were delivered to the pathologist immediately without
malignant fibrous histiocytoma surrounding the common femoral artery with
invasion to artery and vein on magnetic resonance imaging (MRI; case 13).
(b) Corresponding angiogram shows the impression of the superficial femoral
artery and vein en bloc with that segment of the common, superficial, and
deep femoral artery and vein. (c) Reconstruction of the arterial supply
to the leg by interposing an autologous contralateral saphenous vein graft
from the external iliac to the superficial femoral artery with reimplantation
of the main stem of the deep femoral artery to the vein graft after muscle
group resection. Due to maintenance of the greater saphenous vein, no venous
reconstruction was required, (d) Histology section demonstrates invasion
of the arterial wall by sarcoma.
(Please click on images
Course, and Current Status of Patients
revision for hematoma day 1, wound necrosis
mo, lung metastases
and graft infection, omentoplasty, venous graft occluded at 6 mo with persistent
infection, explantation of both prostheses, iliacopopliteal bypass
66 mo, lung and soft tissue metastases
vein thrombosis, revision for hematoma at 2 mo
14 mo, lung, bone, brain metastases
for bleeding day 1, delayed wound healing
27 mo, lung metastases, tuberculosis
39 mo, lung metastases, systemic chemotherapy
day 1, myocardial infarction
of arterial graft resulting in amputation day 19
10 mo, lung metastases
35 mo, recurrent lung metastases,
vein replacement occluded at 3 mo without symptoms
27 mo, lung metastasectomy at 22 mo after systemic chemotherapy
34 mo, lung metastasectomy at 24 mo after systemic chemotherapy
lymphedema Grade I-II
27 mo, lung metastasectomy at 23 mo after systemic chemotherapy
thrombectomy arterial and venous graft day 6
21 mo, lung metastases with systemic chemotherapy
fistula closure at 10 weeks
lymphedema Grade I, stent for arterial graft stenosis at 15 mo
for resected arterial segments had to be performed (Table 2). Femoropopliteal
reconstruction was the most common single type (n = 9: contralateral saphenous
vein, n = 4; ePTFE 6 mm or 8 mm [Goretex], n = 5). In three patients, the
reconstruction ended up above-knee; in six patients, the distal anastomosis
was at the below-knee level. In six patients, the reconstruction started
from the external iliac artery to the femoral or popliteal artery (ring-walled
ePTFE, 8 mm, Gore-tex) positioned through the obturator foramen in two
cases. One reconstruction required a vein graft to reimplant the major
branch of the deep femoral artery (Fig. 1). In another patient (9), a bypass
was inserted from the common iliac crossing over to the common femoral
artery. In three patients with primary tumors of the popliteal fossa, saphenous
vein grafts from the supragenual to the infragenual popliteal artery were^the
method of choice.
In 11 patients a reconstruction
of resected vein segments also was required. This was achieved by using
an allograft in four patients, by using of an autologous contralateral
saphenous vein graft in six patients, and by direct suturing in another
patient. Nine reconstructions started at the below-knee level and ended
up either above the knee (n = 4) or at the femoral level (n = 5). In another
patient, a bypass from the femoral to the external iliac vein was implanted
through the obturator foramen.
Soft tissue coverage
Four patients required myocutaneous
flaps to cover the area of vascular reconstruction due the extent of resection
and to provide sufficient nutrient blood supply (patients 6, 14, 15, and
18). We used the rectus abdominis, latissimus dorsi, and parascapular flap.
Two patients required a split thickness skin graft.
All patients were followed
routinely by computed tomography scan or magnetic resonance imaging (MRI)
of the area of the primary tumor and by bidimensional X-ray of the chest
every 3 months in the first and second postoperative years and at 6 months
intervals thereafter. All data were collected prospectively.
Survival analysis was performed
with the method of Kaplan and Maier16
by using the SPSS program (Mi-croSoft Windows release 6.1; SPSS Inc., Chicago,
IL). Survival data were calculated from the start of treatment. Operative
mortality was included in the analysis of survival and was excluded from
calculating survival rates for patients who were free from local or distant
Tumor Type and Grade, Location
and Previous Therapy, Extent of Tumor Resection, and Vascular Reconstruction
malignant fibrous histiocytoma; TNF-ILP: isolated, hyperthemic limb perfusion
with rhu tumor necrosis factor alpha; HT: regional radiofrequence hyperthermia;
m: muscle; VG: vein graft, autologous, contralateral saphenous vein; AG:
aliograft (Goretex, 6 mm or 8 mm); RT: radiotherapy.
and history of prior treatment
treatment, surgical procedure (muscles and nerves resected), vessel repair,
and plastic reconstructive measures
canal, residual tumor after R2 resection
group and vastus intermedius m., superficial femoral artery and vein (AG)
and adductor m.
and adductor compartment, femoral nerve, superficial femoral artery and
thigh, femoral vein occlusion
group and quadriceps, external iliac and superficial femoral artery and
and adductor group, residual after R2 resection
group resection, external iliac artery plus common femoral vein (direct
residual after Rl resection
wall and groin, external iliac and common femoral artery (AG), rectus abdominis
fossa, third recurrence
gastrocnemius m., tibial nerve, popliteal artery and vein (VG), myocutaneous
canal, popliteal artery occlusion
group, epineurectomy sciatic nerve, superficial femoral artery and vein
group, vastus, sartorius, and gracilis m., superficial femoral artery and
pelvis and groin, recurrence iliac vein occlusion, systemic chemotherapy
resection plus vessels, common iliac to common femoral artery and vein
canal/popliteal fossa, systemic chemotherapy for lung metastasis, lung
adductor and flexor group, superficial femoral artery and vein (VG)
canal residual after R2 resection
group, superficial femoral artery and vein (VG)
group lower limb
chemotherapy, TNF-ILP; soleus/gastrocnemius m., popliteal and anterior
tibial artery and vein (vein patch)
common femoral artery and vein, extracompartmental
rectus, gracilis and adductor group, external iliac to superficial femoral
artery and vein (VG), reimplantation deep femoral artery
fossa second recurrence fast neutron RT
gastrocnemius m., epineurectomy tibial and peroneal nerve, popliteal artery
and vein (VG), myocutaneous latissimus dorsi flap
second recurrence, fast neutron RT
wall, groin dissection, femoral nerve, external iliac and common femoral
artery and vein (AG), myocutaneous rectus abdominis flap
and Hunter's canal, residual after R2 resection
compartmentectomy, superficial femoral artery and vein (VG)
RT (66 Gy), quadriceps compartmentectomy, superficial femoral artery and
third recurrence, neutron RT, iliac vein occlusion
chemotherapy and HT; abdominal wall resection and groin dissection, femoral
nerve, external iliac to superficial femoral artery and vein (VG), myocutaneous
rectus abdominis flap
and Hunter's canal
flexor and adductor group thigh, superficial femoral artery and vein (VG)
fossa, infiltration to bone
flexor muscles, proximal tibia, peroneal nerve, endoprosthesis, popliteal
artery and vein (VG)
Histologic typing of the
tumors identified malignant fibrous histiocytoma in six patients, leiomyosarcoma
in five patients, and liposarcoma in four patients, whereas alveolar type,
synovial sarcoma, mesenchymoma, and embryonic type accounted for the tumors
in the remaining five patients (Table 2). The degree of tumor differentiation
was determined according to Trojani et al.17
and was classified as well differentiated in 2 patients, moderately differentiated
in 3 patients, and poorly differentiated in another 15 patients.
In all patients, resection
resulted in a radical procedure with negative margins (RO-resection) that
were confirmed by the pathologist's report. Three resection specimens showed
no viable tumor cells after multi-modality therapy.
Invasion of the neurovascular
bundle was confirmed histologically in all patients. Invasion of the wall
of the resected vein was detected histologically in nine patients, and
specimens from two other patients showed that the vein was surrounded by
tumor without invasion. A vein thrombosis was documented in four patients.
Infiltration to the arterial wall was observed in resection specimens from
nine patients: at the adventitial level in four patients, at the muscular
layer in another four patients, and to the intima in one patient. Three
other patients showed tumor infiltration to a perivascular scar following
previous operations. The tumor in one patient was classified according
to its origin from the vessel wall (vascular leiomyosarcoma; patient 1).
A tumorous infiltration to nerves was confirmed in seven patients.
Mortality and Morbidity
One patient (7) died postoperatively
due to occlusion of the anterior branch of the left coronary artery (autopsy
finding). Three patients suffered from major complications (see Table 1).
Amputation as a result of graft failure was required for patient 8. She
presented with occlusion of an autologous femoropopliteal venous graft
6 hours postoperatively that was managed successfully by thrombectomy and
intraarterial rh-TPA lysis. Reocclusion occurred on postoperative day 17.
She had started with her contraceptive pill without informing the nursing
staff. Thrombectomy and intraarterial lysis could not reverse ischemia
of the lower limb and forced above-knee amputation. In patient 2, wound
infection led to occlusion of the prosthesis replacing the femoral vein.
After explantation of the prostheses, arterial blood supply to the lower
leg was maintained by an extraanatomical iliacopopliteal (be-low-knee)
bypass. Thrombectomy of both arterial and venous grafts was required for
patient 15, but his further course was uneventful.
Minor revisions for complications
such as postoperative bleeding or lymphatic fistula were required in Jour
patients. The overall wound complication rate was 4 of 19 patients (21%).
Overall and Disease Free
The overall median survival
of our patients was 48 months (range, 7+ to 69 months; 95% confidence interval
[CI], 24-72 months), with a mean survival of 45 months (95% CI, 32-57 months;
Fig. 2). Seven patients remained completely free from recurrence with
a median follow-up of 29
months (7-69 months). Currently, another two patients are free from disease
at 31 and 34 months postoperatively. Both have undergone resection of recurrent
tumor with curative intent and have been free from disease for more than
12 months. In one of them, a solitary lung metastasis was resected 24 months
after operation, whereas another patient had resection of a local recurrence
that was detected 15 months postoperatively.
Eight patients died 10-66
months after onset of treatment. Reasons for death were progressive lung
metastases in seven patients and a caverna from tuberculosis following
systemic chemotherapy for lung metastases in another patient.
Local Tumor Relapse
Four patients (4, 10, 11,
and 14) developed a local recurrence at 15, 18, 20, and 27 months postoperatively.
The mean survival time free from locoregional recurrence was 54 months
(95% CI, 42-66 months;
Fig. 3), the median survival
has not yet been reached. The 5-year local relapse free survival rate was
68.3%. In three patients (10, 11, and 14), the recurrence was amenable
to a second RO-resection with no further local recurrence. However, two
patients developed systemic metastases prior to their local relapse (patients
10 and 11). Two patients of those who developed locally recurrent disease
had been treated previously for a recurrent (patient 14) or an incompletely
resected (patient 4) primary tumor.
Eight patients are free
from distant metastases 7-69 months after surgery. Another 11 patients
developed distant metastases, and seven of them have died. The median survival
time free from distant recurrence is 24 months (95% CI, 13-34 months),
and the mean survival time is 30 months (95% CI, 18-43 months;
In all patients who developed
distant recurrences, the lung was the site of metastases. The patients
were treated by systemic chemotherapy, and four of them underwent resection
of their lung lesions. Other sites that were involved by metastatic spread
were bone (n = 1), skin (n = 2), and brain (n = 1).
Limb-saving surgery is the
treatment of choice for soft tissue sarcoma of the extremities.18
Amputation as an initial treatment can be justified only in cases of infiltration
of joints or intractable exulceration and pain. In locally advanced tumors,
combined modality approaches, such as pre- or postresection radiotherapy
and preoperative systemic or regional chemotherapy, are recommended for
Hyperthermic ILP provides another effective treatment to induce regression
of initially irresectable sarcomas.24,25
However, even if tumor shrinkage by preoperative therapy can be achieved
surgically, adequate resection with clear margins remains a challenging
The patient's prognosis
is influenced predominantly by the degree of differentiation of the primary
tumor and an adequate surgical resection margin. Microscopic residual disease
induces local recurrence and impairs overall survival.26-30
Especially in recurrent disease, the extent of tumor infiltration into
surrounding tissue often cannot be determined definitely. Thus, decisions
about adequate surgical margins seem particularly difficult in tumors close
to or invading major vessels and nerves. Even within the past few years,
such a condition was regarded as cause for amputation.31
However, resection and reconstruction of these vessels is feasible and
may allow limb salvage without compromise in surgical radicality.
Our policy during the past
years was to extend resections for locally advanced sarcomas into neighboring
structures to obtain safe margins of clearance. We used preoperative combined-modality
therapies, like hyperthermic ILP with rhTNFa and melphalan,32
or systemic chemotherapy combined with regional radiofrequency hyperthermia,14,15
or hyperfraction-ated radiotherapy to down-stage the tumor in order to
facilitate resection. In this setting, vascular surgical techniques are
aimed at the en bloc resection of the neurovascular bundle involved. A
violation of the tumor border can be avoided, and safe resection margins
can be obtained. The necessity to resect arterial and venous vessels is
obvious due to tumor involvement of their common fascial sheath; thus,
subadven-titial dissection during tumor excision may be inadequate.
In 1977, Fortner et al.11
were the first to describe monobloc soft tissue and vascular resection
with arterial and venous reconstruction for soft tissue sarcoma of the
thigh in six patients as a measure to avoid lymphedema or postthrombotic
syndrome in contrast to earlier patients in whom no reconstruction had
been performed. Later, Impararato et al.33
treated 13 patients for soft tissue and bone sarcomas with en bloc resection
of the tumor with surrounding muscle groups, including major vessels and
nerves. In all patients, the artery was replaced by an autologous sa-phenous
vein graft from uninvolved extremities. Venous reconstructions were performed
in three patients in whom the deep femoral vein had to be resected. Another
study24 reported on
21 patients with soft tissue sarcoma of the lower limb invading major vessels,
which were resected along with surrounding muscles and replaced with vascular
grafts. With the exception of one patient, all patients were resected without
We achieved a radical resection
(negative margins, RO) in all patients. Consequently, only one patient
(13; Fig. 1) underwent postoperative radiotherapy, because he took part
in a study combining adjuvant chemotherapy for high grade lesions with
radiotherapy for all extracompartmental tumors greater than 5 cm. Four
patients had local recurrences. Two of them were noted among the group
of patients who were referred initially for recurrent or residual tumor.
Three recurrent tumors could be excised with curative intention by minor
resections. Another patient did not require any treatment of the local
relapse due to disseminated systemic tumor spread. In the series by Karakousis
et al.,34 a single
local recurrence occurred in 12 patients with histologically uninvolved
margins who receiving no adjuvant irradiation. Of the nine patients who
received adjuvant irradiation, two developed local recurrence, and one
required amputation. In another study of seven patients who were treated
with monobloc sarcoma and vessel resection, local recurrence was observed
in two patients, requiring disarticulation.11
The low recurrence rate in our study with no amputation required for local
relapse may have been due to the intensive multimodality treatment concept,
which resulted in a histologically complete remission in resected specimens
from three patients.
Overall survival following
surgical treatment of soft tissue sarcoma invading to neurovascular bundles
Local recurrence free survival
following surgical treatment of soft tissue sarcoma invading to neurovascular
bundles (Kaplan-Meier estimates).
FIGURE 4. Survival free from
distant metastases after treatment of soft tissue sarcoma invading to neurovascular
bundles (Kaplan-Meier estimates).
Wound healing problems and
postoperative bleeding occurred during our initial experience, probably
due to excessive anticoagulation in view of the vessel grafts. Three of
the first four patients developed wound healing complications due to hematoma
formation and inadequate muscle coverage of the reconstruction. In our
series, the wound infection rate was 21%, whereas other authors reported
a rate of 24%.34 In
patients who have been treated more recently, the use of free or pedicled
myocutaneous flaps has helped us to avoid these problems. The majority
of patients experienced a completely uneventful course.
It has been argued that,
after resection of the external iliac vein or superficial femoral vein,
a venous bypass would be mandatory to avoid lymphedema.11
From our experience, the capacity of the saphenous vein and its accompanying
lymphatics is sufficient to drain the venous system if it can be preserved
without compromising radicality. It should to be kept in mind that harvesting
of the contralateral saphenous vein also may damage the lymphatic bundle,
contributing to edema formation. With the exception of two patients, there
was no incapacitating edema in any of the extremities. Mild edema could
be treated very successfully with elastic support. Two patients suffered
from lymphedema at 24 months and 16 months post-operatively (cases 13 and
18), with a circumference discrepancy of 3 cm that might have been due
to postoperative irradiation in patient 13. The rate of postoperative lymphedema
formation in our series seems to be lower than that reported after combined
modality that included high dose radiotherapy despite resection of the
If the saphenous vein is
absent or must be resected for radicality reasons together with the superficial
femoral vein, then it is mandatory to restore the venous drainage of the
limb. However, the use of allografts to replace the vein is hampered by
a patency rate at 6 months of less than 50%.36
One series on venous grafts reported that only two grafts stayed open for
3 and 4 months, and there were two infections, one of which necessitated
amputation.33 On the
other hand, the formation of collateral vessels develops rapidly. Once
occlusion of the venous bypass occurs more than 4 weeks after the operation,
no attempt for salvage is required.
Two patients with major
complications required multiple surgeries (patients 2 and 8). In one patient,
occlusion of the arterial reconstruction resulted in amputation-a course
that also has been reported in other series.33
Autologous vein grafts in reversed position always should be preferred
to allografts due to a decreased risk of wound infection, less risk in
case of hematoma development, and less interference of an-ticoagulation
policy with additional oncologic treatment. Muscle coverage of the entire
vascular reconstruction is considered critical for maintaining their integrity.
Soft tissue defects in the groin or thigh can be covered by local muscle
flaps. Free microvascular flaps may be advisable if large popliteal resections
expose vessel grafts.37,38
We used the latissimus dorsi
and parascapular flap in
a second procedure about 1 week after initial resection and vascular replacement.
A two-step procedure was chosen so that there would be no risk of a free
myocutaneous flap due to an occlusion of the arterial or venous implant.
However, an immediate free tissue transfer may lead to a shorter hospital
Thus, the perioperative
morbidity accompanying vessel resection and reconstruction seems to be
acceptable in relation to the underlying disease, to the extent of the
operative procedure, and to the operative procedure itself. The competitive
approach combines vessel-preserving surgery with high dose radiotherapy.
The wound infection rate of patients undergoing mul-timodality treatment
of sarcoma including intraoper-ative or postoperative brachytherapy or
external beam radiation seems to be slightly greater (38-48%).35,40-43
Furthermore, a rate of 9% of radiation neuritis was reported.21
However, brachytherapy provided
excellent local control of advanced soft tissue sarcomas. Randomized trials
reported that brachytherapy significantly improved local control in high
grade lesions but demonstrated no impact in patients with low grade tumors.44
This is particularly helpful in the group of vessel-invasive tumors. In
a study of soft tissue sarcomas invading to neurovascular bundles, the
in-field local relapse rate was 21%.21
The local recurrence rate in series with vessel resection ranged from 14%
to 20%,11,33,34 which
also was true in this series. Thus, the local control rates of aggressive
surgery or "limited" surgery combined with extensive radiotherapy seem
to be comparable. Preoperative down-staging by, e.g., systemic chemotherapy
or ILP followed by extended surgery versus limited surgery with intra-
and postoperative radiotherapy are competitive approaches in patients with
sarcomas invading to neurovascular bundles.
The decision whether or
not to resect vessels in close proximity to soft tissue sarcoma depends
on how exactly a true invasion by tumor can be assessed pre-or intraoperatively.
Recent developments in MRI techniques seem to be promising for providing
more accurate information on the distance between the border of the tumor
and vessels or nerves.45
However, until such reliable data are available, vessel resection is recommended
if there remains doubt whether a safe margin of clearance can be obtained
by dissecting perivascular or perineural tissue.
Nerve involvement in vessel-invasive
tumors often creates a problem due to infiltration of the common fascial
sheath. In five patients, we had to sacrifice major nerves (femoral, tibial,
and peroneal). Nerve preservation often is not a feasible option for radicality
reasons. However, an insensate foreleg, e.g., after resection of the sciatic
nerve, creates a significant problem if the saphenous nerve does not contribute
enough to the sensibility of the foot. Limb salvage by resection of vessels
and major nerves that leaves behind an extremity without tactile sensations
is not advisable. In these cases, amputation still may be the treatment
During the further course
of their disease, in none of our patients was local tumor relapse a major
problem. However, distant metastases developed in 11 patients (55%), and
another two patients already had lung metastases preoperatively. This high
incidence is interrelated to the proportion of high grade tumors, their
deep location, and often their size.6,46
The rate of distant metastases in high grade soft tissue sarcoma was reported
up to 45%.5,7,8,47
In another report on tumors invading to neurovascular bundles, it was 30%.21
Lung metastases developed predominantly, but there were also other distant
metastases to the pelvis, brain, and spine.
Consequently, the major
cause of death in this group of patients remained metastatic disease but
not local recurrence.48
The median survival in this series was 48 months, which is a marked improvement
compared with previous data reporting 26 months33
that have been confirmed by other authors.34
The survival rate of the extended surgery approach also seems to be higher
than the 32% reported for patients undergoing tumor resection alone without
preoperative multimodal therapy.8
Thus, our greatest challenge is to improve control of distant disease.
Despite excellent local control rates following limb-sparing procedures,
greater than 50% of patients ultimately will die of their disease.49
In many instances, only
the availability of vascular surgical techniques allows radical surgery
for primary or recurrent sarcoma. The limits of resectability, however,
are extended in such a way that they necessitate plastic reconstruction
of large soft tissue defects. There is a growing need for a plastic surgeons
to join the medical team in order to treat soft tissue sarcoma successfully.
In conclusion, this study
has demonstrated that the involvement of major vessels by soft tissue sarcomas
of the extremities is not an indication for amputation by itself. After
en bloc resection of major vessels, the local recurrence and 5-year survival
rates parallel those of patients with soft tissue sarcomas that do not
require vessel resection. Long term local relapse free survival could be
provided after preoperative combined modality therapy followed by extended
surgery. Vascular resection and reconstruction as well as plastic reconstructive
measures enabled radical resections with negative margins in all patients
and confirmed three histologically complete tumor remissions.
This aggressive surgical
approach is in competition with more limited resections combined with in-tra-
and postoperative radiotherapy. The morbidity data of the more surgical
approach seem to be favorable and make irradiation techniques available
in cases of local recurrence. The limitation for long term disease free
survival, however, is distant metastases. Therefore, new systemic therapies
must be developed to control disseminated tumor growth.
Boring CC, Squires TS, Tong
T, Montgomery S. Cancer statistics, 1994. CA Cancer J din 1994;44:7-26.
Karakousis CP, Emrich LJ, Rao
U, Khalil M. Limb salvage in soft tissue sarcomas with selective combination
of modalities. EurJ Surg Oncol 1991;17:71-80.
Williard WC, Hajdu SI, Casper
ES, Brennan MF. Comparison of amputation with limb-sparing operations for
adult soft tissue sarcoma of the extremity. Ann Surg 1992;215:269-75.
Rosenberg SA, Tepper J, Glatstein
E, Costa J, Baker A, Brennan MF, et al. The treatment of soft-tissue sarcoma
of the extremities. Prospective randomized evaluation of limb-sparing surgery
plus radiation therapy compared with amputation and the role of adjuvant
chemotherapy. Ann Surg 1982:305
Pisters PW, Leung DH, Woodruff
J, Shi W, Brennan MF. Analysis of prognostic factors in 1,041 patients
with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996;14:1679-89.
Coindre JM, Terrier P, Bui NB,
Bonichon F, Collin F, Le Doussal V, et al. Prognostic factors in adult
patients with locally controlled soft tissue sarcoma. A study of 546 patients
from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol
Rooser B, Berg NO, Ranstam J,
Rydholm A, Willen H. Prediction of survival in patients with high-grade
soft tissue sarcoma. Int Orthop 1990; 14:199-204.
Ruka W, Emrich LJ, Driscoll
DL, Karakousis CP. Prognostic significance of lymph node metastasis and
bone, major wessel, or nerve involvement in adults with high-grade soft
tissue sarcomas. Cancer 1988:62:999-1006.
Shiu MH, Hilaris BS, Harrison
LB, Brennan MF. Brachyther-apy and function-saving resection of soft tissue
sarcoma arising in the limb. Int J Radiat Oncol Biol Phys 1991;21:1485-92.
Hug EB, Spiro IJ, Cole DJ, Suit
HD. Combined surgery and radiotherapy for conservative management of soft
tissue sarcomas. Rec Res Cancer Res 1995; 138:47-55.
Fortner JG, Kim DK, Shiu MH.
Limb-preserving vascular surgery for malignant tumors of the extremities.
Arch Surg 1977; 112:391-4.
Eggermont AM, Schraffordt Koops
H, Klausner JM, Kroon BB, Schlag PM, Lienard D, et al. Isolated limb perfusion
with tumor necrosis factor and melphalan for limb salvage in 186 patients
with locally advanced soft tissue extremity sarcomas. Ann Surg 1996;224:756-65.
Reichardt P, Lentzsch S, Hohenberger
P, Dorken B. Dose intensive treatment with ifosfamide, epirubicin, and
filgras-tim for patients with metastatic or locally advanced soft tissue
sarcoma. ] Clin Oncol 1998;16:1438-43
Reichardt P, Tilgner J, Mapara
MY, Hohenberger P, Dorken B. Dose-intensive chemotherapy with or without
stem cell support for adult patients with advanced soft tissue sarcoma.
Issels RD, Bosse D, Abdel Rahman
S, Starck M, Panzer M, Jauch KW, et al. Preoperative systemic etoposide/ifosfamide/doxorubicin
chemotherapy combined with regional hyperthermia in high-risk sarcoma:
a pilot study. Cancer Chemother Pharmacol 1993;31(Suppl 2):S233-7.
Kaplan EL, Maier P. Nonparametric
estimation from incomplete observations. } Med Statist Assoc 1958;53:457-81.
Trojani M, Contesso G, Coindre
JM, et al. Soft tissue sarcoma of adults; study of pathological prognostic
variables and definition of a histopathological grading system. Int J Cancer
Williard WC, Collin C, Casper
ES, Hajdu SI, Brennan MF. The changing role of amputation for soft tissue
sarcoma of the extremity in adults. Surg Gynecol Obstet 1992;175:389-96.
Engel CJ, Eilber FR, Rosen G,
Selch MT, Fu YS. Preoperative chemotherapy for soft tissue sarcomas of
the extremities: the experience at the University of California, Los Angeles.
Cancer Treat Res 1993;67:135-41.
Suit HD, Spiro I. Role of radiation
in the management of adult patients with sarcoma of soft tissue. Semin
Surg Oncol 1994; 10:347-56.
Zeiefsky MJ, Nori D, Shiu MH,
Brennan MF. Limb salvage in soft tissue sarcomas involving neurovascular
structures using combined surgical resection and brachytherapy. Int J Radiat
Oncol Biol Phys 1990;19:913-8.
Fein DA, Lee WR, Lanciano RM,
Corn BW, Herbert SH, Hanlon AL, et al. Management of extremity soft tissue
sarcomas with limb-sparing surgery and postoperative irradiation: do total
dose, overall treatment time, and the surgery-radiotherapy interval impact
on local control? Int J Radiat Oncol Biol Phys 1995:32:969-76.
Wanebo HJ, Temple WJ, Popp MB,
Constable W, Aron B, Cunningham SL. Preoperative regional therapy for extremity
sarcoma. A tricenter update. Cancer 1995;75:2299-306.
Lienard D, Ewalenko P, Delmotte
JJ, Renard N, Lejeune FJ. High-dose recombinant tumor necrosis factor alpha
in combination with interferon gamma and melphalan in isolation perfusion
of the limbs for melanoma and sarcoma. J Clin Oncol 1992;10:52-60.
Rossi CR, Vecchiato A, Foletto
M, Nitti D, Ninfo V, Fornasi-ero A, et al. Phase II study on neoadjuvant
hyperthermic-antiblastic perfusion with doxorubicin in patients with intermediate
or high grade limb sarcomas. Cancer 1994;73:2140-6.
Choong PF, Gustafson P, Rydholm
A. Size and timing of local recurrence predicts metastasis in soft tissue.
Acta Or-thop Scand 1995;66:147-52.
Emrich LJ, Ruka W, Driscoll
DL, Karakousis CP. The effect of local recurrence on survival time in adult
high-grade soft tissue sarcomas. / Clin Epidemiol 1989:42:105-10.
Heslin MJ, Gaynor JJ, Newman
E, Wolf RF, Woodruff J, Casper ES, et al. Effect of perioperative blood
transfusion on recurrence and survival in 232 primary high-grade extremity
sarcoma patients. Ann Surg Oncol 1994; 1:189-97.
Herbert SH, Corn BW, Solin LJ,
Lanciano RM, Schultz DJ, McKenna WG, et al. Limb-preserving treatment for
soft tissue sarcomas of the extremities. The significance of surgical margins.
Lewis JJ, Leung D, Heslin M,
Woodruff JM, Brennan MF. Association of local recurrence with subsequent
survival in extremity soft tissue sarcoma. J Clin Oncol 1997; 15:646-52.
Lawrence WD, Donegan W, Natarajan
N, Mettlin C, Beart R, Winchester DP. Adult soft tissue sarcoma. Ann Surg
Eggermont AM, Schraffordt Koops
H, Lienard D, Kroon BB, van Geel AN, Hoekstra HJ, et al. Isolated limb
perfusion with high dose tumor necrosis factor alpha in combination with
interferon gamma and melphalan for irresectable extremity soft tissue sarcomas:
a multicenter trial. J Clin Oncol 1996;14:2653-65.
Imparato A, Roses D, Francis
K, Lewis M. Major vascular reconstructions for limb salvage in patients
with soft tissue and skeletal sarcomas of the extremities. Surg Gynecol
Karakousis CP, Karmpaliotis
C, Driscoll DL. Major vessel resection during limb-preserving surgery for
soft tissue sarcoma. World J Surg 1996:20:345-50.
Stinson SF, DeLaney TF, Greenberg
], Yang JC, Lamport MH, Hicks JE, et al. Acute and long-term effects on
limb function of combined modality limb sparing therapy for extremity soft
tissue sarcoma. Int J Radiat Oncol Biol Phys 1991;21:1493-9.
Okadome K, Muto Y, Eguchi H,
Kusaba A, Sugimachi K. Venous reconstruction for iliofemoral venous occlusion
facilitated by temporary arteriovenous shunt. Long-term results in nine
patients. Arch Surg 1989; 124:957-60.
Steinau HU, Hussmann J, Hebebrand
D. Rekonstruktion-smoglichkeiten nach erweiterter Resektion maligner Weich-teilgeschwulste
[Reconstructive possibilities after extensive resection of malignant soft
tissue tumors]. Chirurg 1993;64:517-26.
Evans GR, Black JJ, Robb GL,
Baldwin BJ, Kroll SS, Miller MJ, et al. Adjuvant therapy: the effects on
microvascular lower extremity reconstruction. Ann Plast Surg 1997;39:141-4.
Reece GP, Schusterman MA, Pollock
RE, Kroll SS, Miller MJ, Baldwin BJ, et al. Immediate versus delayed free-tissue
transfer salvage of the lower extremity in soft tissue sarcoma patients.
Ann Surg Oncol 1994; 1:11-7.
Engin K, Leeper DB, Cater JR,
Thistlethwaite AJ, Tupchong L, McFarlane JD. Extracellular pH distribution
in human tumours. Int} Hyperthermia 1995;11:211-6.
Dalton RR, Lanciano RM, Hoffman
JP, Eisenberg BL. Wound complications after resection and immediate postoperative
brachytherapy in the management of soft-tissue sarcomas. Ann Surg Oncol
Arbeit JM, Hilaris BS, Brennan
MF. Wound complications in the multimodality treatment of extremity and
superficial truncal sarcomas. / Clin Oncol 1987;5:480-8.
Alekhteyar KM, Leung DH, Brennan
MF, Harrison LB. The effect of combined external beam radiotherapy and
brachytherapy on local control and wound complications in patients with
high-grade soft tissue sarcomas of the extremity with positive microscopic
margin. Int J Radiat Biol 1996:36:321-4.
Pisters PW, Harrison LB, Leung
DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective
randomized trial of adjuvant brachytherapy in soft tissue sarcoma. / Clin
Panicek DM, Go SD, Healey JH,
Leung DH, Brennan MF, Lewis JJ. Soft tissue sarcoma involving bone or neurovascu-lar
structures: MR imaging prognositc factors. Radiology 1997;205:871-5
Heise HW, Myers MH, Russell
WO, Suit HD, Enzinger FM, Ed-mondson JH, et al. Recurrence-free survival
time for surgically treated soft tissue sarcoma patients. Cancer 1986;57:172-7.
Potter DA, Kinsella T, Glatstein
E, Wesley R, White D, Seipp C, et al. High-grade soft tissue sarcomas of
the extremities. Cancer 1986:58:190-205.
Heslin MJ, Woodruff J, Brennan
MF. Prognostic significance of a positive microscopic margin in high-risk
extremity soft tissue sarcoma: implications for management. / Clin Oncol
Spiro IJ, Rosenberg AE, Springfield
D, Suit H. Combined surgery and radiation therapy for limb preservation
in soft tissue sarcoma of the extremity. Cancer Invest 1995; 13:86-95.