Laparoscopic Adrenalectomy for Metachronous Metastasis fromRenal Cell Carcinoma
Stephane Bonnet Æ Sebastien Gaujoux Æ Mahaut Leconte ÆJean-Marc Thillois Æ Frederique Tissier Æ Bertrand Dousset
Published online: 12 March 2008
� Societe Internationale de Chirurgie 2008
Abstract
Background Metachronous adrenal metastases (AM)
from renal cell carcinoma (RCC) are rare. We report our
experience of surgical resection in this setting, with par-
ticular respect to laparoscopic approach and long-term
outcome.
Methods A retrospective review of 11 patients who
underwent adrenalectomy for metachronous AM from
RCC was conducted between 2002 and 2005 in a tertiary
referral center.
Results CT scan findings were those of an adrenal mass
ranging from 2 to 13 cm in diameter with a basal density of
12 to 28 Hounsfield Units and strong heterogeneous
enhancement following contrast injection. The surgical
procedure consisted of controlateral (n = 5), ipsilateral
(n = 2), and bilateral (n = 1) laparoscopic adrenalectomy,
whereas three patients underwent controlateral open adre-
nalectomy for adrenal mass [10 cm. Nine patients were
recurrence-free with a median follow-up of 34 months. In
the remaining two patients, lung metastases were discov-
ered at postoperative months 28 and 11, respectively. The
former patient is alive and free of disease recurrence
32 months after lung metastasis resection, whereas the
latter is currently being treated with sunitinib.
Conclusions This study confirms that prolonged overall
and disease free-survival can be achieved in selected
patient after laparosocpic adrenalectomy for AM from
RCC
Introduction
Renal cell carcinoma (RCC) accounts for 90–95% of renal
tumors and represents 2% of all adult malignant tumors [1].
The majority of patients are diagnosed at an early stage [2]
(I-II of the American Joint Committee on Cancer classifi-
cation) and come under radical nephrectomy with or
without adrenal-sparing surgery [3]. After primary tumor
resection, approximately 25% of patients develop
metachronous metastasis [4, 5], and among these\2% will
present with metastasis confined to the adrenal gland [6, 7].
Although recent series have reported prolonged survival
after open adrenalectomy for adrenal metastasis (AM) [6,
8], there has been no previous report specifically focusing
on the laparoscopic approach for AM from RCC.
In the present study, we analyzed 11 consecutive
patients who underwent surgical resection of metachronous
AM from RCC, with particular respect to laparoscopic
approach and the long-term outcome.
Patients and methods
From February 2002 to September 2005, 134 adrenalec-
tomies (113 laparoscopic and 21 open procedures) were
performed at Cochin University hospital. Eleven patients
who underwent adrenal surgery for metachronous AM
from RCC were the basis of this study. Metachronous
S. Bonnet � S. Gaujoux � M. Leconte � J.-M. Thillois �B. Dousset (&)
Department of Digestive and Endocrine Surgery, Hopital
Cochin, AP-HP, Universite Paris Descartes, 27, rue du Faubourg
Saint-Jacques, 75014 Paris, France
e-mail: [email protected]
F. Tissier
Department of Pathology, Hopital Cochin, AP-HP, Universite
Paris Descartes, Paris, France
123
World J Surg (2008) 32:1809–1814
DOI 10.1007/s00268-008-9539-3
metastases were defined as AM diagnosed with a 6-month
delay after primary RCC resection, and ‘‘time to diagnosis’’
was defined as the time interval between nephrectomy and
AM diagnosis. Time to surgery was defined as the time
elapsed between the diagnosis of AM and adrenal surgery.
Follow-up after renal surgery included physical examina-
tion, thoracic and abdominal CT scan every 6 months, and
bone scintigraphy every year. Patients’ data and charac-
teristics of primary surgery for RCC are reported in
Table 1. All initial CT were available to assess adrenal
glands at the time of renal surgery and disclosed no evi-
dence of adrenal abnormalities. The diagnosis of AM from
RCC was suspected in any case of newly diagnosed adrenal
mass, characterized by basal CT density superior to 10
Hounsfield Units (HU), strong or heterogeneous vascular
enhancement following contrast injection, and/or growing
size on sequential imaging studies. Percutaneous adrenal
biopsy was ruled out for prevention of tumor seeding. All
patients underwent preoperative staging with conventional
technetium-99 m methylene diphosphate whole body bone
scan and 18F-fluorodeoxyglucose (18F-FDG) positron
emission tomography/computed tomography (PET/CT)
imaging, and none of them had evidence of extra-adrenal
disease. The following hormonal determinations were
performed in all patients: plasma ACTH and serum corti-
sol, 17-OHP, DHEA-S, testosterone, plasma renin activity
and aldosterone in supine and upright positions, 24-h uri-
nary-free cortisol, and catecholamine excretion. Lateral
transperitoneal laparoscopic adrenalectomy was decided
for the eight patients with adrenal mass inferior to 10 cm
and confined within the enlarged adrenal gland. All of them
were placed in lateral decubitus position. Four trocars were
used. The laparoscopic adrenalectomy was performed as
previously described [9] with the greatest care for pre-
vention of tumor disruption and total clearance of
periadrenal fat tissue. All specimens were extracted intact
within a bag. In return, the laparoscopic approach was
judged unreasonable and conventional open adrenalectomy
more adequate for the three patients with AM [10 cm.
Each patient in whom adrenalectomy induced Addison’s
disease (bilateral adrenalectomy or unilateral adrenalec-
tomy after adrenal nonsparing nephrectomy) was placed on
life-long adrenal glucocorticoid and mineralocorticoid
replacement therapy after surgery. All patients were
reviewed every 6 months with physical examination, tho-
racic and abdominal CT scan, and yearly bone
scintigraphy.
Results
All 11 patients had normal adrenal glands on preoperative
CT scan before renal surgery and adrenal metastases were
diagnosed 6 to 42 months after renal surgery. All these
lesions had a basal density ranging from 12 to 28 (median,
24) HU and strong heterogeneous enhancement following
contrast injection on CT scan.
Three patients had newly diagnosed incidentaloma
\2 cm, characterized by negative 18F-FDG PET/CT
uptake and spontaneous density inferior to 20 HU on initial
Table 1 Operative and pathological data of original renal tumor
Patient Age at
surgery (yr)
Sex Surgical
approach
Location Side Tumor
size (cm)
Ipsilateral
adrenalectomy
Locoregional extent TNM Furhman
grade
1 58 M Transperitoneal
laparotomy
Middle Right 5 Yes Renal vein invasion pT3bN0M0 Grade 3
2 71 F Retroperitoneal Upper Right 6.5 Yes – pT1N0M0 Grade 3
3 78 M Retroperitoneal Lower Right 6 No – pT1N0M0 Grade 2
4 67 M Retroperitoneal Middle Right 7 No Renal vein invasion
Perirenal fat invasion
pT3bN0M0 Grade 3
5 59 M Retroperitoneal Lower Left 9 No Perirenal fat invasion pT3aN0M0 Grade 4
6 73 M Transperitoneal
laparoscopy
Lower Right 7 Yes – pT1N0M0 Grade 3
7 70 M Retroperitoneal Upper Right 5 No Renal vein invasion
Perirenal fat invasion
pT3bN0M0 Grade 2
8 59 M Transperitoneal
laparotomy
Middle Right 8 No Renal vein invasion pT3bN0M0 Grade 2
9 61 M Transperitoneal
laparotomy
Middle Right 5 Yes Renal vein invasion pT3bN0M0 Grade 3
10 74 M Transperitoneal
laparoscopy
Lower Left 5 No – pT1N0M0 Grade 2
11 57 M Transperitoneal
laparoscopy
Upper Right 5 No Renal vein invasion
Perirenal fat invasion
pT3bN0M0 Grade 3
1810 World J Surg (2008) 32:1809–1814
123
CT scan for two of them. Therefore, these three patients
were followed 10 to 13 months before adrenal surgery,
until increasing size on sequential CT scan led to surgical
decision. Five patients had evidence of an adrenal mass
ranging from 2.5 to 8 cm in diameter, four of which had
increased uptake on 18F-FDG PET/CT imaging. These
eight patients underwent laparoscopic controlateral
(n = 5), ipsilateral (n = 2), and bilateral (n = 1) (see
patient 8, Fig. 1) adrenalectomy. Three patients lost for
follow-up after RCC surgery presented with an adrenal
mass ranging between 12 and 13 cm, with typical features
of malignancy, including large size, irregular mass delin-
eation, necrotic areas, strong heterogeneous enhancement
following contrast injection, and strong 18F-FDG PET/CT
uptake. AM characteristics including operative and patho-
logical data are summarized in Table 2.
The duration of the laparoscopic procedure ranged from
70 to 110 minutes for controlateral lesions and was longer
for ipsilateral (90–180 min) or bilateral (170 min) laparo-
scopic adrenalectomy, in view of surgical constraints due
to previous nephrectomy. Three patients underwent open
controlateral adrenalectomy for metastases of 12 and
13 cm (see patient 9, Fig. 2). One of these patients required
en bloc resection of left adrenal gland, left pancreas, and
spleen because of local invasion. He had compensated
HBV liver cirrhosis and developed postoperative ascites
and, furthermore, needed blood transfusion. There were
otherwise no postoperative complications, and none of the
patients died after surgery. The median duration of hospital
stay after laparoscopic adrenalectomy was 3.4 (range, 3–4)
days and was longer (8, 10 and 18 days) after open surgery.
In all cases, pathological examination confirmed the diag-
nosis of metastasis related to RCC. All patients had a
complete macroscopic resection, without capsular disrup-
tion, and negative margin (R0 resection). All patients are
alive after a median follow-up of 34 (range, 15–60)
months, and none of them have had a local relapse or port-
site metastasis. Nine patients remained free of disease
recurrence. Two are alive with lung metastases discovered
at postoperative months 28 (patient 1) and 11 (patient 9).
The former patient underwent elective resection of lung
metastases and is alive 32 months after thoracic surgery
Fig. 1 CT scan of patient 8
reveals a 2-cm enhanced nodule
(white arrow) in the left adrenal
gland and a 3.5-cm enhanced
nodule (black arrow) in the right
adrenal gland. On the right side,
macroscopic view of the opened
surgical specimen
World J Surg (2008) 32:1809–1814 1811
123
Ta
ble
2O
per
ativ
ed
ata,
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ho
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a,an
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sis
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erit
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llo
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(rig
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AN
ED
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terv
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om
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sis
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terv
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om
dia
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alm
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ith
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evid
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dis
ease
1812 World J Surg (2008) 32:1809–1814
123
with no evidence of recurrent disease. The latter is cur-
rently being treated with sunitinib with objective response
after five cycles.
Discussion
Adrenal metastases are among the least frequent sites of
metastatic disease with a global incidence rate of 2–10%
[6, 7] in patients with metastatic RCC. In a recent series of
1179 patients treated for RCC, the global incidence of
adrenal metastasis was 3.7%, and they were ipsilateral in
1.9%, controlateral in 1.5%, bilateral in 0.3%, synchronous
with the renal tumor in 2.7%, and metachronous in only 1%
of patients [6].
The reported prognosis for patients with metastatic RCC
is very low with a median survival of 6 to 12 months and a 2-
year survival rate of 10–20% [3]. Recent advances in newly
targeted therapeutic agents, such as sunitinib, have paved the
way to encouraging response rate and progression-free sur-
vival for metastatic RCC [10, 11]. Nevertheless, surgical
resection of metastases from RCC is the only potential
curative treatment in selected patients [6, 12–14], with 5-
year disease-free survival reported after open adrenalectomy
for metachronous AM from RCC [6, 12]. Several series [15–
20] of 12 to 33 patients have reported encouraging results
after laparoscopic resection of AM from various origin,
including 1 to 13 patients from RCC. To our knowledge, the
present study is the first to specifically focus on AM from
RCC. Thus, among the 11 selected patients with metachro-
nous AM, laparoscopy surgery was judged feasible in 8
patients (72%) with excellent disease-free survival of 87%
after a 39-month follow-up.
The diagnosis and accurate management of AM from
RCC raises several questions. The first issue is to accu-
rately differentiate metastasis from primary adrenal tumor
in patients with a past history of RCC. Thanks to recent
advances in noninvasive imaging techniques, the diagnosis
of AM has become easier on thin-slice multidetector CT:
basal CT density superior to 10 HU, strong vascular
enhancement following contrast injection and growth with
time on sequential imaging studies [6]. In ours series, the
basal density for AM from RCC ranged from 12 to 28 HU
with a median value of 24 HU, which is on the lower side
for a malignant process. To our knowledge, there are no
published data on basal density of AM from RCC on CT
scan, even though a recent series reported a relatively low
median basal density (35 HU) of primary RCC [21].
It has been our policy to consider laparoscopic adrenal-
ectomy for any newly diagnosed incidentaloma of[2 cm, or
adrenal mass growing in size, in patients with previous RCC,
regardless of the basal density of adrenal lesion on CT scan,
even in the setting of previous adrenal nonsparing nephrec-
tomy for AM\10 cm. Although radiologically guided fine-
needle aspiration cytology is nearly 100% specific for the
diagnosis of adrenal metastases [22, 23], we were reluctant to
consider this procedure before potential curative surgery, in
return to the high risk for tumor disruption, and tumor
seeding [19] along the needle tract.
The second issue for the management of AM from RCC
is to assess the safety of laparoscopic resection, in view of
the strong reluctance to consider this approach for primary
Fig. 2 CT scan of patient 9
with asymptomatic polycystic
liver disease reveals a 13-cm
enhanced adrenal mass with
irregular demarcation, strong
heterogeneous enhancement
following contrast injection
(black arrow). On the right side,
macroscopic view of the opened
surgical specimen
World J Surg (2008) 32:1809–1814 1813
123
adrenal cancer [10]. Laparoscopic adrenalectomy has
become the technique of choice for surgical resection of
benign adrenal lesions, even for tumors up to 10 cm in size
[16, 24]. In our experience, all patients with small lesions
underwent laparoscopic resection of AM, with free-surgi-
cal margins, no conversion to laparotomy, and no tumor
disruption. Laparoscopic ipsilateral adrenalectomy for AM
from RCC (3/8 patients) was technically more difficult but
appeared feasible. In contrast, three patients with bulky
adrenal metastases underwent open surgery to ensure
adequate curative (R0) resection. None of our eight patients
experienced port site or local recurrence, highlighting the
safety of laparoscopic surgery, although one patient
developed lung metastases. In a recent review of the lit-
erature [16], the reported incidence of local recurrence
after laparoscopic resection of adrenal metastases from
various primaries was anecdotal for port site recurrence
(only one case reported) and ranged from 0% to 20% for
local recurrence. In our experience, laparoscopic adrenal-
ectomy for adrenal metastases seems to provide
oncological benefits compared with results reported after
open procedure [16–18, 25].
Conclusions
All newly diagnosed incidentalomas following RCC
[2 cm, or that will grow in size with time, should be
considered for laparoscopic surgical resection. Even in the
setting of ipsilateral AM, laparoscopic adrenalectomy
provides faster recovery with good oncological outcome, at
least similar to that observed after open surgery. In return,
we believe that bulky AM [10 cm in size should be
resected by conventional surgery to ensure safe R0 resec-
tion. Nevertheless, the question still remains whether
targeted therapy with sunitinib should be proposed before
or after resection for metachronous metastatic disease as it
has been shown with high-risk GIST with favorable out-
come after adjuvant imatinib [26].
Acknowledgments Thanks to Pierre RATIER for help in preparing
the manuscript and Mrs. Christine FORTIER for technical assistance
and patient follow-up.
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