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Laparoscopic approach of pediatric adrenal tumors
Raquel Oesterreich1(D . Maria Florencia Varela1 . Juan Moldes1 . Pablo Lobos1
Accepted: 13 July 2022 / Published online: 25 July 2022 @ The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022
Abstract
Purpose To analyze the role of laparoscopic surgery for the management of pediatric adrenal tumors (AT).
Methods Retrospective analysis of children diagnosed with AT, operated laparoscopically during 2003-2020. The strategy differed according to tumor extension. AT <6 cm were resected. Locally advanced tumors (L2) or>6 cm were biopsied. Results N = 28. Complete tumor resection (R0) in 20 (71%), tumor biopsy in 8 (R2). Age (median): 28.8 months (2 months-18 years). 14/28 left-sided, 2 bilateral. Median operating time: 78 min (45-180). Mean tumor size (for resec- tions): 4 cm (2.5-6). Tumor pathology: neuroblastoma (n=17), Ganglioneuroma (n=7), Adrenocortical carcinoma (n=1), Osteosarcoma metastasis (n=1), Pheochromocytoma (n=1), Venous malformation (n=1). Mean hospital stay: 2.5 days (1-3). Mean follow up: 65.5 months (24-192). Overall survival and event-free survival were 86 and 75%, respectively (5 years event-free survival for neuroblastoma: 33% [intermediate risk], 16.6% [high risk]. No surgery-related mortality.
Conclusion Laparoscopic surgery for adrenal tumors is safe. Laparoscopic biopsy is useful for unresectable tumors when a percutaneous approach is not possible. With the proposed selection criteria, the laparoscopic approach should be the first option for resection of small and localized AT in pediatrics.
Keywords Adrenal tumor · Neuroblastoma . Pediatric . Laparoscopic . Minimally invasive surgery . Adrenalectomy
Introduction
Adrenal tumors can arise from both the cortical and the medullary portion of the gland. This origin is responsible for the clinical presentation in some patients. In other cases, an adrenal mass can be accidentally found on imaging tests. The treatment is directly influenced by the etiology of the tumor, ranging from observation only to surgical resection [1,2].
When initial resection is not indicated, an adequate biopsy must be done to obtain tissue for proper diagnosis and treat- ment. Although a less invasive biopsy procedure through a
percutaneous needle biopsy is often recommended, this is not always possible, for example, due to the inability to reach the tumor via a safe path, inadequate tissue sampling to yield an accurate diagnosis, or lack of a skilled interventional radi- ologist [3, 4]. For those clinical scenarios, a laparoscopic biopsy may be a good option [5].
Tumor resection often requires large incisions when an open approach is used. The laparoscopic approach offers minimally invasive access to the adrenal compartment with great in situ visibility. Currently, laparoscopic adrenalec- tomy is widely used as a first-choice approach in adults with benign tumors and some selected cases of malignant tumors [6, 7]. This approach offers a clear benefit by reducing post- operative pain, and shortening hospital stay, with earlier recovery and better long-term cosmetic results [7-9].
Expertise in laparoscopic adrenalectomy has not been widely reported in pediatrics as in adult surgery, because of the low incidence of adrenal tumors in this population, the variety of differential diagnoses, and the high rate of malig- nancy [10, 11]. Neuroblastoma is the most common adrenal tumor in children. Locally advanced tumors need an initial biopsy [12]. When resection is indicated, large tumor size and the frequent involvement of adjacent organs and vessels
☒ Raquel Oesterreich raquel.oesterreich@hiba.org.ar
Maria Florencia Varela maria.florencia.varela@cchmc.org Juan Moldes juan.moldes@hiba.org.ar Pablo Lobos pablo.lobos@hiba.org.ar
1 Pediatric Surgery Division, Hospital Italiano de Buenos Aires, Tte. Gral. J. D. Perón, 4190 Buenos Aires, Argentina
will warrant an open surgery in the vast majority of adrenal neuroblastomas [11, 13].
Reports on laparoscopic adrenalectomy in children have shown that this approach could be considered in a significant proportion of adrenal lesions, both for biopsy and for resec- tion of either benign or malignant tumors [14, 15]. Given the variety of possible diagnoses and extent of disease, the selection criteria for a laparoscopic approach need further discussion.
The present study aims to analyze and report our results with a minimally invasive approach for the diagnosis and treatment of children with adrenal tumors, with a focus on the patient selection criteria as the basis for the decision- making process.
Methods
A retrospective, descriptive study was performed. The data were extracted from the institutional electronic clinical records and the local pediatric surgical oncology database. All data were anonymized, to comply with the personal data institutional policy. The study population included all consecutive pediatric patients with adrenal tumors either biopsied or resected through a laparoscopic approach in the Department of Pediatric Surgery of a single tertiary center, from November 2003 to March 2020, with a minimum follow up of 24 months. Patients treated through an open approach were not included.
Initial management
Indications for surgery were decided in a multidisciplinary team.
- Observation only: since 2014, patients younger than 18 months with adrenal tumors were included in a con- servative “observation only” protocol, locally designed based on the previously published reports. An ultrasound evaluation was performed at diagnosis, monthly dur- ing the first year and every 3 months during the second year until the age of 18 months. Surgical resection was avoided unless the parents did not consent to the obser- vation-only protocol, growth during this period, or tumor persistence at 18 months of age [16].
- Biopsy: a laparoscopic approach was performed as the first option for tissue sampling for histological, immu- nohistochemical, and molecular biology studies when an image-guided percutaneous core needle biopsy was not possible. A biopsy was indicated according to preop- erative imaging-based staging, i.e., patients with image- defined risk factors (IDRFs) or metastasis (stage L2, M, and MS of the INRG Staging System) [17].
- Tumor resection: upfront tumor resection was indicated for localized tumors in absence of IDRFs at initial eval- uation (L1 of the INRG Staging System) [17], and in tumors with a diameter under 6 cm according to crite- ria previously reported [15, 18]. Neoadjuvant chemo- therapy followed by delayed resection was preferred in L2 tumors, L1 tumors larger than 6 cm in diameter, and patients with metastatic disease. Surgical resection of larger lesions or persistent L2 tumors was performed through a classic open approach and these patients were excluded from this study.
A proposed algorithm illustrating the decision-making process at the presentation of a pediatric patient with an adrenal mass is shown in (Fig. 1).
Surgical technique
A transperitoneal laparoscopic approach was used, estab- lishing a left/ right semi-lateral decubitus position, with the affected side up-raised around 60° through a patient posi- tioner [19]. The camera was placed through a periumbilical incision (5- or 12 mm port) and 2 to 3 working ports (3 or 5 mm) were placed in the epigastrium, flank, and hypochon- drium (Fig. 2A, B). In right-sided lesions, an extra port was used for liver retraction (Fig. 2B). The port size was chosen based on the age and weight of the patient. Bleeding control at the biopsy site was achieved using monopolar and argon beam coagulation, adding hemostatic agents like Surgicel® Original Hemostat (Ethicon, USA, Cod: 1953), if needed. The surgical specimen was removed in a custom-made surgi- cal bag through the periumbilical incision.
Analyzed variables were age, sex, presentation at diag- nosis, affected side, imaging methods for diagnosis, tumor pathology, surgical technique (biopsy or resection), opera- tive time, length of hospital stay, surgical complications, follow-up time, overall survival (OS), and event-free sur- vival (EFS).
Follow up and further multimodal therapies for patients with malignant tumors were carried out by the same multi- disciplinary team.
Statistical analysis
For the baseline features of the population, the quantitative variables were expressed as mean (standard deviation), and the qualitative variables as absolute numbers (percentages). For the survival analysis, the Kaplan-Meier method was performed using R version 3.6.3 [20] and RStudio 2019 “survival” package [21].
Ethical considerations: Institutional review board (IRB) was obtained for this research (Protocol Nº 3318), within
ADRENAL TUMOR
Preoperative Cross Sectional Imaging Studies (IDRFs)
Absent
Present
Upfront Tumor Resection
Tumor Biopsy
Image guided Core needle biopsy available
< 6 cm
> 6 cm
Yes
No
Signs of ACC *
OPEN APPROACH
Core needle Biopsy
LAPAROSCOPIC TUMOR BIOPSY
+
Evaluate Open or Laparoscopic Approach (Imaging and surgeon expertise)
LAPAROSCOPIC TUMOR RESECTION
Delayed Surgery needed
the framework of principles promulgated in the Declaration of Helsinki, determined by the World Medical Association.
Results
During the study period, 28 patients met the inclusion criteria. Male patients accounted for 64% (n=18) of the cases. The average and median age at surgery were 59 and 28.8 months respectively (range 2 month-18 years). The left adrenal gland was the most frequently affected (n=14) and 2 patients had bilateral lesions.
The clinical presentation was diverse. The patients pre- sented with different clinical symptoms like abdominal pain in 7 (27%), palpable mass in 4 (15%), hypertension and viri- lization (1 case each), and 3 (12%) patients had a prenatal presentation. In one case, prenatal ultrasound showed a left
adrenal mass coincidentally with a right multicystic kidney. The other patients presented an incidental finding during studies for other conditions (follow up for osteosarcoma, screening for urinary malformations, scoliosis, etc.)
Different imaging modalities were indicated for diagno- sis. Abdominal ultrasound was the initial method used in all patients, followed by a CT scan in 26 (93%). Other meth- ods were MRI (n=7, 27%) and MIBG scintigraphy (n=13, 46%).
From 2014, when the observation-only protocol started, 10 patients were eligible for the observation-only protocol, as they were younger than 18 months of age at diagnosis. In five cases tumor resection was performed during the follow up because parents refused conservative management (n= 1), tumor growth during the observation period (n=2), and persistence of tumor at 18 months of age (n=2).
SERIE CON CTE. EV.
mm
O2
O2
53.8 mm
26.7 mm
30.6 mm
A. Left tumor
18:06.27
29-Sep-2006
2
35.51 mm,
B. Right tumor
Two patients had bilateral adrenal masses. The first case was prenatally diagnosed and confirmed as neuro- blastic tumor by elevated urinary catecholamine metab- olites. After 18 months-observation period, complete regression of the right mass was observed, and laparo- scopic left adrenalectomy was performed due to tumor persistence confirming a ganglioneuroma. The second case was a 3-year-old boy in whom an upfront left lapa- roscopic adrenalectomy and right tumor biopsy was per- formed; after confirming high-risk neuroblastoma (N-myc amplification and bone marrow infiltration), induction chemotherapy was indicated, and a delayed laparoscopic right tumorectomy was performed, with preservation of normal gland tissue. This patient is alive with no evidence of disease at 160 months of follow up, and no signs of adrenal insufficiency.
Tumor biopsies
Laparoscopic biopsy was performed in eight patients (29%) (Table 1). The mean age was 38.6 months (range 9-72 months). The decision to biopsy was based on the
positive IDRFs and tumor diameter larger than 6 cm in all cases. Delayed tumor resection was performed after induc- tion chemotherapy, through an open approach in all of them. The median operative time for laparoscopic biopsy was 85 min (range 60-180 min) from induction to complete reversal of anesthesia.
All the biopsy procedures were completed laparoscopi- cally. Immediate and medium-long term postoperative com- plications, as well as intraoperative adverse events, were reg- istered in our series. A jejunal perforation was diagnosed on a high-risk neuroblastoma patient 24 h after a laparoscopic biopsy. Retrospectively, we could speculate that an acci- dental thermal lesion from monopolar coagulation was the cause of this perforation; further complications accounted for a dismal evolution, including multiple enterocutaneous fistulas, requiring the use of total parenteral nutrition for 6 months; extensive intestinal resection at the time of the delayed tumor resection was accomplished; this patient is currently asymptomatic, without parenteral nutrition, and disease-free at three years of postoperative follow up.
All tumor samples were adequate for diagnosis: neuro- blastoma (n=6; 75%), ganglioneuroma (n=2; 25%).
| 1. Age/Sex | 2. Tumor side | 3. Op. time | 4. Tumor pathology | 5. Tumor size | 6. Compl | 7. Follow up | 8. Status |
|---|---|---|---|---|---|---|---|
| 22/F | Right | 90 | Neuroblastoma | 6.7 cm | No | 61 | Alive |
| 60/M | Left | 75 | Ganglioneuroma | 6.2 cm | No | 40 | Alive |
| 72/M | Left | 150 | Neuroblastoma | 9.6 cm | No | 39 | Alive |
| 47/M | Right | 60 | Neuroblastoma | 8.2 cm | No | 24 | DOD |
| 15/M | Left | 60 | Neuroblastoma | 9.9 cm | No | 52 | Alive |
| 48/F | Left | 110 | Neuroblastoma | 6.8 cm | No | 118 | Alive |
| 9/M | Left | 80 | Neuroblastoma | 7.2 cm | No | 30 | Alive |
| 36/M | Right | 180 | Neuroblastoma | 13.1 cm | Yes (jejunal perfo- ration) | 28 | Alive |
All patients were Hispanic
(1) Age (months). (3) Operation time (minutes). (7) Follow up (months)
DOD: Death of disease
Further laparoscopic resection was not possible in any case because of the persistence of IDRFs, except the previ- ously mentioned bilateral neuroblastoma, where the right adrenal mass was resected laparoscopically after biopsy and chemotherapy.
Tumor resections
Laparoscopic tumor resection was performed in 20 patients (71%) (Table 2), with bilateral asynchronous resection in one case. Upfront resection was performed in all cases, except the second tumor in the bilateral case. The mean tumor diameter was 4 cm (range 2.5-6 cm). The median opera- tive time was 78 min (range 45-180 min) from induction to complete reversal of anesthesia.
In one case prenatally diagnosed with a left adrenal tumor and a right multicystic kidney, a right nephrectomy and left adrenalectomy were performed in a single transabdominal laparoscopic procedure.
A gross total resection was achieved in all cases. All sur- gical procedures were completed laparoscopically, except for the case of an adolescent with a right adrenal metastasis from osteosarcoma, with a tumor highly adhered to adjacent inferior vena cava (IVC). During dissection, a small tear in the IVC produced significant bleeding; immediate conver- sion to laparotomy allowed successful bleeding control. No other intraoperative complications were registered.
Pathology results of resected specimens showed the fol- lowing distribution: neuroblastoma (n=17; 61%), gangli- oneuroma (n=7; 27%), adrenocortical carcinoma (n=1), metastasis of osteosarcoma (n= 1), pheochromocytoma (n=1), and venous malformation (n=1). The mean hospi- tal stay was 2.5 days (range 1-3 days), except for the previ- ously mentioned patient that had a jejunal perforation with an unusually prolonged hospital course.
All operations were performed by a surgeon-in-training, such as a pediatric surgery resident, or a pediatric surgical oncology fellow, with direct supervision of an experienced pediatric surgical oncologist (P. L.). A few technical key points during minimally invasive surgery (MIS) for adre- nalectomies are worth mentioning: (1) one of the keys of a successful surgery is to achieve complete resection, regard- less of the approach, carrying out the dissection on a mac- roscopically disease-free tissue, and being as aggressive as needed while balancing related morbidity. If the tumor is adhered to vessels, we use the vascular wall as a surgical plane of dissection to ensure complete resection; (2) Ves- sel sealing energy devices (i.e., Harmonic® shears, EnSeal® tissue sealer, Ethicon Endosurgery, OH, USA or LigaSure®, Covidien, CO, USA) are usually employed to avoid or con- trol bleeding, while preventing thermal injury to contigu- ous structures. However, for larger vessels, clips or bipolar coagulation may be required. (3) Right adrenal resection can be challenging given the fact that the adrenal vein drains directly into the retro-hepatic vena cava on this side. For this scenario, a liver port is especially useful to provide opti- mal exposure and facilitates the first move, which should be incising the right triangular ligament located right above the tumor, to expose the inferior vena cava and have it readily available for clamping. Once the short right adrenal vein is identified, it can be divided between double 5 mm locking polymer clips; (4) Once the mass has been resected, a speci- men retrieval bag can be introduced through the camera port for tumor extraction, by enlarging the umbilical incision or via a Pfannenstiel incision, to avoid potential mass rupture and tumor spread. Using the same rationale, tumor mor- cellation to achieve extraction through small incisions was not performed in our patients to allow adequate histologic margin assessment and to avoid bag rupture; (5) In addi- tion to the preoperative staging, evaluation of the regional
| 1. Age/sex | 2. Tumor side | 3. Op. time | 4. Tumor pathology | 5. Tumor size | 6. Complica- tions | 7. Follow up | 8. Status |
|---|---|---|---|---|---|---|---|
| 3/M | Left | 60 | Neuroblastoma | 3 cm | No | 133 | Alive |
| 19/F | Left | 50 | Adrenal carcinoma | 4 cm | No | 176 | Alive |
| 42/M | Bilateralª | 120 | Neuroblastoma | 4 cm/ | No | 160 | Alive |
| 2 cm | |||||||
| 3/M | Left | 180b | Neuroblastoma | 4.5 cm | No | 152 | Alive |
| 216/F | Right | 180 | Osteosarcoma metas- tasis | 5.5 cm | Yes (bleeding) | 2 | DOD |
| 132/M | Left | 50 | Ganglioneuroma | 4 cm | No | 193 | Alive |
| 132/F | Right | 60 | Ganglioneuroma | 6 cm | No | 204 | Alive |
| 9/M | Left | 180 | Neuroblastoma | 4.7 cm | No | 7 | DOD |
| 168/F | Left | 120 | Ganglioneuroma | 6 cm | No | 89 | Alive |
| 21/M | Bilateral“ | 78 | Ganglioneuroma | 2.6 cm | No | 48 | Alive |
| 132/F | Left | 60 | Ganglioneuroma | 6 cm | No | 63 | Alive |
| 16/F | Right | 70 | Neuroblastoma | 3.5 cm | No | 18 | DOD |
| 168/F | Left | 68 | Ganglioneuroma | 4.5 cm | No | 77 | Alive |
| 36/F | Right | 58 | Neuroblastoma | 5 cm | No | 54 | Alive |
| 15/M | Left | 66 | Neuroblastoma | 4.7 cm | No | 47 | Alive |
| 192/M | Right | 70 | Pheochromocytoma | 4 cm | No | 47 | Alive |
| 12/M | Right | 45 | Neuroblastoma | 5 cm | No | 57 | Alive |
| 2/M | Right | 120 | Venous malformation | 4 cm | No | 22 | Alive |
| 4/M | Right | 150 | Neuroblastoma | 2 cm | No | 19 | Alive |
| 20/M | Right | 100 | Neuroblastoma | 3.5 cm | No | 18 | Alive |
All patients were Hispanic
(1) Age (months). (3) Operation time (minutes). (7) Follow up (months)
aLeft laparoscopic resection with right laparoscopic biopsy. Owing to high-risk neuroblastoma, the right tumor did chemotherapy and later lapa- roscopic resection
bContralateral nephrectomy for a multicystic kidney in the same operation
“Right tumor regressed spontaneously. Left tumor resected laparoscopically after 18 months of follow up
DOD: death of disease
nodes was always performed before completion of the proce- dure, but since our patients selected for laparoscopic resec- tion didn’t have enlarged nodes, none of them needed node biopsy, sampling or resection. This is probably related to the selected group of tumors resected laparoscopically that were <6 cm without IDRF.
All symptomatic patients have resolved their symptoms. All patients with benign lesions survived without recurrence. Both patients with bilateral lesions showed no evidence of adrenal insufficiency and are under close follow up.
Children with malignant lesions were treated and fol- lowed by the multidisciplinary team. The patient with meta- static osteosarcoma received rescue chemotherapy, at 8 days postoperative, when the pathology diagnosis was confirmed. The patient subsequently died due to disease progression. The adrenocortical carcinoma case was a female patient with onset of virilization symptoms at 19 months, with no associ- ated syndrome. The work-up showed a 4 cm tumor without metastases. After complete surgical resection of a stage I
localized mass, the patient did not receive further treatment. Altered hormone levels returned to normal values after sur- gery, as well as virilization clinical features. Molecular and genetic testing were not performed on this patient, primarily due to lack of availability over the study period.
Seventeen patients were diagnosed with neuroblastoma: six high-risk, three to intermediate-risk, and eight to low-risk groups. Intermediate-risk group patients received a chemo- therapy regimen according to COG-ANBL0531 protocol (Carboplatin, Etoposide, Doxorubicin, Cyclophosphamide) [22]. High-risk group patients were treated according to the protocol published by the Latinamerican Pediatric oncol- ogy group (“NBT2014 SAHOP/GALOP protocol”) and, in a similar way as COG protocol [23], they received local tumor irradiation and high-dose chemotherapy with autolo- gous bone marrow transplantation. Further treatment with anti-GD2 immunotherapy was performed in three patients [23]. Laparoscopic resection was performed in 10 neuro- blastoma patients, achieving gross total resection in all of
Full population
Neuroblastomas
Ganglioneuromas
Kaplan-Meier survival probability
1.00
Kaplan-Meier Survival probability
1.00
Kaplan-Meier survival probability
1.00
0.75
0.75
0.75
0.50
0.50
0.50
0.25
0.25
0.25
0.00
0.00
0.00
0
2
4
6
8
10
12
14
16
0
2
4
6
8
10
12
0
2
4
6
8
10
12
14
16
A
Time (years)
B
Time (years)
C
Time (years)
them with no local relapses documented so far. The average postoperative time to the initiation of adjuvant chemotherapy was 7 days, the time needed for the pathological analysis of the resected specimen.
The mean follow-up period was 65.5 months (range 7-192 months). Four patients died (14%, n=3) high-risk neuroblastoma, and n = 1 metastatic osteosarcoma). All deaths occurred within 2 years after tumor resection (Fig. 3). No surgery-related deaths occurred in the study. Four high- risk neuroblastoma patients presented tumor relapse (bone marrow, skull, and retroperitoneal lymph nodes), three of them dying for disease progression. No tumor relapse was observed in the adrenocortical carcinoma patient after a follow-up period of 176 months.
Five-year overall survival (OS) was 100% for interme- diate risk and 50% for high-risk neuroblastoma. Five-year event-free survival (EFS) was 33% for intermediate risk and 16.6% for high risk.
Discussion
The laparoscopic approach for surgical treatment of AT was first described in 1992 for adult patients [24]. Since then, it has been widely used and is currently considered the procedure of choice for adrenalectomy in that popula- tion [7]. In 1996 Yamamoto reported for the first time a laparoscopic operation in a pediatric patient with neuro- blastoma [25] and in 2001 Mirrallié et al. demonstrated in a small case series that laparoscopic adrenalectomy is a feasible and safe option for children. After them, various authors have proposed this approach for AT [26-28]. How- ever, probably due to the low incidence of AT in children, most of the case series reported in the literature have a relatively small number of patients [9]. This approach has been rarely reported by Latin American groups, and the
actual preference for the laparoscopic approach by pedi- atric surgeons in our continent is unknown.
The clinical presentation of AT in children is diverse [2, 27] and patients with advanced malignancies may present with overt clinical symptoms [28]. It is important to note that a thorough physical examination may raise the suspi- cion of a genetic disorder associated with a predisposition to certain tumors. A close clinical follow up and an ultrasound surveillance protocol can allow an early diagnosis of AT in this population [29-31].
The age distribution in our series is consistent with the literature. A relevant finding is the high proportion of malig- nant tumors, especially at very young ages, which is related to neuroblastomas typically affecting the adrenal glands [32, 33].
Some of the previously recognized advantages of lapa- roscopic adrenalectomy and tumor biopsy compared to the open traditional surgery are related to better intraoperative visualization, quick recovery to daily activities, early toler- ance to oral feedings, and less postoperative pain, which also results in a shorter hospital stay and better cosmetic results. These advantages become even more relevant when the patient requires adjuvant chemotherapy, as in the case of neuroblastoma [34, 35].
Indications of surgery for children with AT must be dis- cussed within the umbrella of a multidisciplinary specialized team [36]. The eligibility for laparoscopic surgery is deter- mined by the surgical team, in agreement with the oncolo- gists. In patients younger than 18 months, in whom low-risk tumors are almost the rule, observation only protocol with ultrasound surveillance is applied, as previously described to be safe [16, 37]. For older patients, the current recommenda- tion for adrenal tumors without image-defined risk factors is primary resection [11, 15, 32].
For patients with large lesions at the time of diagnosis, a laparoscopic biopsy is an option to obtain an adequate amount of tissue, when an image-guided percutaneous
biopsy is unavailable or unreliable. Although some authors report favorable results with percutaneous core needle biopsy for neuroblastic tumors [38], our experience with this method has not been satisfactory, because the biopsy specimen is often insufficient for histological, immunohis- tochemical, and molecular biology studies. Other authors have also reported this difficulty [4].
When concerning the tumor volume as a criterion for eli- gibility for laparoscopic resection, many authors have pro- posed that this approach should be chosen for tumors with a larger tumor dimension (LTD) under 5 to 7 cm [33]. In our series, all the patients had an LTD under 6 cm. In a recent paper, Gabra et al. have proposed future guidelines for lapa- roscopic resection of neuroblastoma, considering a tumor volume (TV) under 75 ml for patients without IDRF+ [18].
Minimally invasive adrenalectomy can be done using dif- ferent approaches: transperitoneal adrenalectomy (in a lat- eral/semi-lateral or in a supine position) and retroperitoneal adrenalectomy (in a lateral/semi-lateral or in a prone posi- tion). Transperitoneal approaches offer a spacious operative field allowing wider movements of the instruments and more precise dissection of the blood vessels and intra-abdominal organs [9, 19]. Retroperitoneal approaches give direct access to the gland, avoid the need for colon mobilization or liver retraction and reduce the risk of intra-abdominal organ dam- age and adhesions [33, 39]. However, this type of access gives a more limited working space, and for right tumors the vena cava lies behind the adrenal gland when using a right retroperitoneal approach [28, 40]. In any case, supine or prone procedures are useful to resect bilateral tumors avoiding changing the patient’s position during the surgery. Finally, the learning curve for retroperitoneal approaches is an issue for pediatric surgeons because the indications are rare, resulting in rather few reports of retroperitoneoscopy for pediatric adrenalectomies with small patient populations [14, 40-42]. Therefore, the technique should be chosen in accordance with anatomy and the surgeon’s experience [14, 39]. In our series, patients were approached using transperi- toneal access with semi-lateral position for single tumors, and supine position for bilateral interventions.
Our experience shows that the laparoscopic approach for pediatric adrenal tumors can be safely performed by a surgeon in training [43] Previously published reports have focused on the need for advanced laparoscopic expertise in minimally invasive adrenalectomies in children [7, 35, 44]. However, with the patient selection criteria proposed here, we have found the laparoscopic procedures to be easier than expected. Most of the tumors that do not have IDRFs have a well-defined separation from the adjacent organs, facili- tating their resection with blunt dissection. Furthermore, in neuroblastomas or ganglioneuromas, which account for the majority of cases in our study, it has been demon- strated that a microscopic residue does not have an impact
on the long-term results [26, 34]. In our experience, even in procedures in which a surgeon in training is involved, similar operation times to those reported in the literature are achieved [19, 27, 44, 45].
We have presented in our series a metastatic adrenal sar- coma. Only a few reports of laparoscopic management of sarcomatoid adrenal lesions in children have been published to date. Our previous experience with laparoscopic adrenal- ectomies encouraged us to use the same approach with this case, however, we found this tumor to be more adherent to adjacent structures than neuroblastic tumors, with a difficult surgical plane. We would not recommend this approach if a previous diagnosis of sarcoma is suspected, although we underscore that this recommendation should be carefully taken in light of the limited power of a case report [46].
Regarding adrenocortical carcinomas (ACC), previous reports recommend against minimally invasive surgery, because of the recurrence risk as a result of tumor rupture or local spillage, and their low response to chemotherapy [47]. Other authors have reported the safety of laparoscopic tumor resection in these patients. We report a single case of ACC which was successfully resected laparoscopically. The patient had a small mass, and no recurrence has occurred so far.
A wide variety of intraoperative and postoperative com- plications have been described, such as tumor rupture, dia- phragmatic lesions, renal vein thrombosis, inadequate tumor exposure, and bleeding, the most frequently reported event [9, 45]. We report two major complications in our series, one bowel perforation and significant bleeding in another case. Although not exempt from complications, the described approach presented acceptable morbidity, similar to that previously reported (Tables 1 and 2).
An average follow-up period of more than 5 years reported in this study allowed us to estimate the medium and long-term efficacy and safety of the laparoscopic approach in this selected group of patients. Although a high propor- tion of malignant tumors was observed, the mortality was relatively low (14%). Most patient deaths were associated with high-risk neuroblastoma, as reported in similar series [6, 13, 33].
In this study, the laparoscopic approach had no impact on the oncological long-term outcomes. There were no cases of local recurrence after resection of both benign and malignant lesions. Recurrence rates (0 to 2%) have been reported in other series. Overall and event-free outcomes of neuroblas- toma patients correlated well with the assigned risk group [48, 49].
Our study has several limitations that must be acknowl- edged. The small number of patients included does not allow for a deeper analysis and comparison of outcomes between different types of tumors. The retrospective analysis also precludes the comparison of outcomes between laparoscopy
and open or conservative approach. Despite this, in our opin- ion, the current study serves the purpose of further clarifying the pathway of diagnosis, patient selection for laparoscopic surgery, and outcomes of pediatric AT.
Conclusion
Children presenting with an adrenal mass may have differ- ent diagnoses, and several treatment strategies are involved. An adequate decision-making process based on an exhaus- tive preoperative imaging evaluation and a multidisciplinary discussion for each case allow the surgeon to choose the best surgical approach with the lowest morbidity and mor- tality rate. The laparoscopic approach, with all the benefits of a minimally invasive procedure, has shown no negative impact in the long-term results, being in our opinion the first option for the resection of small, not locally advanced adrenal tumors and also for obtaining a tissue sample in selected patients who should start chemotherapy immedi- ately. The proposed algorithm for the selection of patients who benefit from the laparoscopic approach may be useful to guide pediatric surgeons towards a favorable outcome. More collaborative research is required to boost the power of our data and validate the proposed algorithm, in the context of the increasing use of minimally invasive surgery for adrenal tumors in children as an infrequent condition. Multicenter studies, especially prospective, may have a special role in clarifying the role of laparoscopic surgery for adrenal tumors in children.
Acknowledgements The authors would like to thank Dr. Chan Hon Chui for his suggestions to improve the manuscript; Dr. Néstor Forenza for his contribution to the data collection; Dr. Roberto Vagni and Dr. Gastón Elmo for permitting the inclusion of their patients.
Declarations
Conflict of interest The authors declare that this study was conducted in absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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