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Key words:
Neuroblastoma;
Adrenal tumor;
Laparoscopy
Abstract
Background: Laparoscopic resection of adrenal neuroblastoma has become a common alternative to open
surgery. Prior reports have largely focused on short-term operative complications. This study compares longterm oncologic outcomes in children undergoing laparoscopic or open adrenalectomy for neuroblastoma.
Methods: Seventy-nine patients at a single center met inclusion criteria for having adrenal neuroblastoma
and undergoing operative resection. Patients were assigned to high or low/intermediate (L/I) risk groups
based upon Childrens Oncology Group (COG) trial enrollment. Criteria for laparoscopic resection were
absence of vascular encasement and size 5 cm in greatest dimension. Comparison between open versus
laparoscopic groups was performed by Wilcoxon ranked-sum and Fishers exact test. Multivariate Cox
proportional hazard models analyzed the primary outcomes of mortality and recurrence.
Results: In the L/I risk category (N = 30) there was one non-neuroblastoma related death in the open cohort.
Six of 7 patients in the High risk Group who underwent laparoscopic resection had favorable outcomes. Only
higher tumor stage (Hazard Ratio 8.455, P = 0.01) and earlier tumor recurrence were associated with
increased mortality (Hazards Ratio 0.932, P = 0.0002). Among patients who met selection criteria for
laparoscopic surgery there was no difference in mortality or recurrence rates between High risk and L/I risk.
Conclusions: Laparoscopic resection of adrenal neuroblastoma is feasible and can be performed with
equivalent recurrence and mortality rates in L/I risk patients and selected High risk patients. These data
suggest that laparoscopic resection of adrenal neuroblastoma should be considered in patients who meet
selection criteria, irrespective of risk group categorization.
2013 Elsevier Inc. All rights reserved.
1728
that equivalent or superior oncologic outcomes be demonstrated when compared to the gold standard operative
approach. Although no such evidence exists for laparoscopic
resection of adrenal neuroblastomas, this procedure has
increased in popularity over the last decade. With this
study we sought to compare the oncologic outcomes in
patients undergoing laparoscopic resection of adrenal neuroblastoma with those undergoing the historical standard
treatment, open adrenalectomy.
Over the previous decade, a number of reports have been
published documenting the operative feasibility and safety of
laparoscopic adrenalectomy in children [110]. Many of
these studies included patients who had laparoscopic resections of adrenal neuroblastomas and other malignant
lesions. In these reports outcomes focused on operative
parameters such as operative time, length of stay and
complications and suggested that a laparoscopic approach
to adrenal neuroblastomas is feasible and safe in highly
selected patients. Although the literature supports the safety
and feasibility of the laparoscopic approach, few reports
comment on recurrence or overall survival [4,8,10]. Thus, it is
unclear whether the laparoscopic approach confers an
equivalent oncologic outcome to the open, gold standard
approach. Leclair and colleagues reported a predicted
disease-free survival of 84% at 5 years for 45 patients with
abdominal neuroblastoma undergoing laparoscopic resection
[11]. However, there are no studies that compare laparoscopic
to open adrenalectomy with respect to oncologic outcomes of
recurrence and mortality. Furthermore, there are no studies
that compare outcomes in open and laparoscopic surgery in
high versus L/I risk patient groups. The goal of this study was
to compare the clinical outcomes in patients undergoing
laparoscopic versus open adrenalectomy for neuroblastoma.
1. Methods
A retrospective chart review of patients operated on at
The Hospital for Sick Children, Toronto was conducted over
a ten-year period, 19982008, with Ethics Review Board
approval. Data were collected from electronic and paper
medical records. 128 patients were identified as having
neuroblastoma. The seventy-nine patients who had primary
adrenal neuroblastoma were included in this study. Tumor
size was reported as the largest dimension measured by the
radiologist on pre-operative imaging (CT, MRI or ultrasound). As per institutional guidelines, patients were deemed
candidates for laparoscopic resection if the pre-operative
imaging showed no vascular encasement and a tumor with
the greatest dimension 5 cm. For this review, vascular
encasement and size were evaluated on pre-operative
imaging and not prior to neoadjuvant therapy nor at the
time of operative intervention. The majority of the
laparoscopic procedures (83%) were performed in the last
5 years of the study period. Operative times listed were for
the entire operative procedure performed and in certain cases
2. Results
Of the seventy- nine patients eligible for inclusion, 49 were
in the high risk group and thirty in the L/I risk group. In the
Fig. 1
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Risk Group
High (n = 49)
Operative approach
Mean age (mo)
Surgery alone
Median stage [range]
Largest tumor dimension (cm) [range]
OR time (min)
Converted to Open (%)
Transfused (%)
LOS (days)
Average F/U (mo)
Open (n = 42)
41.3 #
n/a
4 [24]
6.8 [1.113.9]
332 #
n/a
18/48 (37%)
11.31
44
Open (n = 19)
22.5 #
4
2 [14,4S]
6.1 [1.414.8]
252 #
n/a
2/13 (26%)
9.47
69
Lap (n = 11)
17.0 #
9
1 [12]
2.4 [1.72.9]
157
1/11 (9%)
0
2.5 #
42
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Table 2
Risk Group
High (n = 49)
Operative approach
Recurrence
Time to recur [range]
Mean time to mortality [range]^
Mortality
Open (n = 42)
17/36 (47%)*#
20 mos [464]
28 mos [6d-104 mos]
21/48 (50%)#
Open (n = 19)
0#
n/a
6 days
1/19 (5%)#
Lap (n = 11)
0
n/a
n/a
0
* = p 0.05 lap v open approach within risk group , # = p 0.05 between High and Low/Intermediate Risk groups undergoing open or laparoscopic
adrenalectomy, ^ = only for patients with mortality, n/a=not applicable. Denominator n when data was unavailable for some patients.
Fig. 2 KaplanMeier Survival Curve. KaplanMeier survival curves for each group: High Open, High laparoscopic (High Lap), L/I Open
and L/I laparoscopic (L/I Lap). Circles represent censored patients.
3. Discussion
Over the past decade, laparoscopic resection of malignant
tumors has become more commonly performed. The
literature suggests that laparoscopic resection of adrenal
tumors, including some malignancies, in children can be
performed with similar early operative outcomes compared
to open resection. Some studies suggest that earlier time to
post-operative feeding and lengths of stay can be accomplished with a laparoscopic approach to adrenalectomy [6,7].
The outcomes pertaining to oncologic events including
neuroblastoma risk groups, recurrence and mortality rates
have been rarely reported in children undergoing laparoscopic adrenalectomy for neuroblastoma.
In this retrospective review, recurrence and mortality rates
in patients undergoing laparoscopic resection, regardless of
COG neuroblastoma risk category, were equivalent to L/I
Risk patients undergoing open resection. We do not believe
that the surgical approach improved the outcome for these
patients, but rather that there may be a subset of high risk
patients who have favorable clinical and biological features
that influence the size of the tumor, response to chemotherapy, and lack of vascular encasement at the time of resection.
Retrospective analyses of surgical data from the International
Neuroblastoma Risk Group (INRG), International Society of
Paediatric Oncology European Neuroblastoma (SIOPEN),
and the German Society for Paediatric Oncology and
Haematology (GPOH) suggest that patients without vascular
encasement on preoperative imaging may have an improved
event-free survival [1417]. Although we did not directly
correlate vascular encasement with events in this review, the
need for blood transfusion and longer operative times are
indicators of a difficult tumor resection that is often
secondary to vascular encasement. Our data similarly show
that these indicators, the need for blood transfusion and
longer operative times, correlated with an increased risk of
tumor recurrence but not with decreased survival. Additionally, we did not collect data on the size of the tumors prior to
neoadjuvant chemotherapy in the high risk laparoscopic
group and therefore cannot determine whether these patients
initially had smaller or more chemotherapy sensitive tumors
when compared to the high risk open group.
It is inherently difficult to compare outcomes between
these treatment groups because of variations in tumor size
and demographics between the cohorts undergoing open
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versus laparoscopic resections. However, the goal of this
study is to highlight the oncologic outcomes in patients with
neuroblastoma who are carefully selected to undergo
laparoscopic adrenalectomy. Currently there is a lack of
evidence to support equivalent or improved oncologic
outcomes for laparoscopic adrenalectomy for neuroblastoma, a procedure that many pediatric surgeons now perform
routinely. This retrospective review provides an evaluation
of survival and recurrence after laparoscopic resection for
adrenal neuroblastoma that includes high risk patients.
Limitations to this study include the small sample size in
the laparoscopic groups and shorter follow-up in the high
risk laparoscopic group. The shorter follow-up time in the
high risk group make predictions of long-term survival less
accurate. However, in the high risk open group, 52% of
deaths and 75% of recurrences occurred within 2 years of
follow up and the median time to relapse in neuroblastoma is
approximately 13 months [18]. Therefore, we would have
expected to observe recurrences and deaths in the high risk
laparoscopic group during a similar time period if laparoscopic resection was associated with an inferior outcome.
Although the small sample sizes limit our analyses, the
results are statistically significant. Further studies with larger
patient numbers are warranted to corroborate and extend the
results of this analysis.
4. Conclusion
Results from this study indicate that laparoscopic
adrenalectomy for neuroblastoma in patients who meet
surgical selection criteria, tumor size smaller than 5 cm and
absence of vascular encasement, is feasible and offers
equivalent progression-free survival and overall survival
regardless of other indicators of risk including age and stage.
These data suggest that laparoscopic resection of adrenal
neuroblastoma should be considered in patients who meet
selection criteria, irrespective of risk group categorization.
References
[1] Romano P, et al. Adrenal masses in children: the role of minimally
invasive surgery. Surg Laparosc Endosc Percutan Tech 2007;17(6):
504-7.
[2] Stanford A, et al. Surgical management of open versus laparoscopic
adrenalectomy: outcome analysis. J Pediatr Surg 2002;37(7):1027-9.
[3] Laje P, Mattei PA. Laparoscopic adrenalectomy for adrenal tumors in
children: a case series. J Laparoendosc Adv Surg Tech A 2009;
19(Suppl 1):S27-9.
[4] Al-Shanafey S, Habib Z. Feasibility and safety of laparoscopic
adrenalectomy in children: special emphasis on neoplastic lesions.
J Laparoendosc Adv Surg Tech A 2008;18(2):306-9.
[5] Castilho LN, et al. Laparoscopic adrenal surgery in children. J Urol
2002;168(1):221-4.
[6] Iwanaka T, et al. Surgical treatment for abdominal neuroblastoma in
the laparoscopic era. Surg Endosc 2001;15(7):751-4.
1732
[7] Iwanaka T, Kawashima H, Uchida H. The laparoscopic approach of
neuroblastoma. Semin Pediatr Surg 2007;16(4):259-65.
[8] de Lagausie P, et al. Laparoscopic adrenal surgery for neuroblastomas
in children. J Urol 2003;170(3):932-5.
[9] Saad DF, et al. Laparoscopic adrenalectomy for neuroblastoma in
children: a report of 6 cases. J Pediatr Surg 2005;40(12):1948-50.
[10] Kadamba P, Habib Z, Rossi L. Experience with laparoscopic
adrenalectomy in children. J Pediatr Surg 2004;39(5):764-7.
[11] Leclair MD, et al. Laparoscopic resection of abdominal neuroblastoma. Ann Surg Oncol 2008;15(1):117-24.
[12] Baker DL, et al. Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Engl J Med 2010;363(14):1313-23.
[13] Strother DR, et al. Outcome after surgery alone or with restricted use of
chemotherapy for patients with low-risk neuroblastoma: results of
Children's Oncology Group study P9641. J Clin Oncol 2012;30(15):
1842-8.