Adrenal masses in children: Imaging, surgical treatment and outcome

ORIGINAL ARTICLE

Adrenal masses in children: Imaging, surgical

treatment and outcome

S‚enol Emre

*

_{, Rahs‚an O}

¨zcan

, Ayten Ceren Bakır

,

Sebuh Kurugoglu

, Nil C

¸omunoglu

_{, Hilal Susam S‚en}

,

Tiraje Celkan

, Gonca Topuzlu Tekant

a

Department of Pediatric Surgery, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Turkey

b_{Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Turkey} c

Department of Medical Pathology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Turkey

d

Division of Pediatric Oncology, Istanbul Okmeydanı Training and Research Hospital, Turkey

e

Department of Pediatrics, Division of Pediatric Haematology and Oncology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Turkey

Received 23 December 2018; received in revised form 6 February 2019; accepted 11 March 2019

Available online 6 April 2019

KEYWORDS

Adrenal mass; Image defined risk

factors; Adrenal cysts; Neuroblastoma; Pheochromocytoma

Abstract Background/objective: This study aims to evaluate the current surgical approach to adrenal masses in the pediatric age group.

Methods: We retrospectively analyzed cases that underwent surgery for adrenal masses be-tween 2007 and 2017. Patients were assessed regarding age, sex, primary diagnosis, image defined risk factors (IDRF), surgical treatment method, complications, duration of hospital stay, and follow-up.

Results: We examined 50 patients who underwent surgery for adrenal mass (mean age: 4.8 years; range: 5 days_{e14 years). For IDRF assessment, Ultrasonography was used in 42,} Computed Tomography in 36, and Magnetic Resonance Imaging in 36 patients. Lesions were present on the right in 25, left in 21, and bilateral in 4 patients. Histopathological findings were neuroblastoma (nZ 29), ganglioneuroma (n Z 6), adrenal cortex tumor (n Z 5), ganglioneur-oblastoma (nZ 4), pheochromocytoma (n Z 3), cyst (n Z 1), and adrenal hematoma (n Z 2). Laparotomy was performed on 37 patients, and laparoscopy on 13 patients. None of the cases had any operative complications.

Conclusion: The crucial factors determining the surgical approach to adrenal masses in pedi-atric cases are the histopathology of the mass, volume, and IDRF. Minimally invasive proced-ures could be reliably performed in appropriate cases.

ª 2019 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

* Corresponding author. Kartaltepe M. Kibris S, 12/8 Bakirko¨y, Istanbul, Turkey. E-mail addresses:senolemre@hotmail.com,senol.emre@istanbul.edu.tr(S‚. Emre).

https://doi.org/10.1016/j.asjsur.2019.03.012

1015-9584/ª 2019 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Available online atwww.sciencedirect.com

ScienceDirect

journal homepage:www.e -asi anjournalsurgery.com e212

1. Introduction

In most pediatric cases, adrenal gland diseases requiring surgery are masses of the adrenal medulla or cortex. While neoplastic masses constitute the most common type, in-fectious, cystic, or hemorrhagic masses could also be observed in the adrenal gland. The most commonly observed neoplastic mass of the adrenal gland in pediatric cases is neuroblastoma of the adrenal medulla, whereas adrenal carcinoma and adenomas, which are tumors of the adrenal cortex, are less frequent.1,2

Reportedly, the clinical status, size of the mass, radio-logical and histopathoradio-logical features affect the selection of the treatment modality in patients detected with adre-nal masses.3 In this regard the image-defined risk factors were developed for evaluation of resectability of neuro-blastoma and neuroblastic tumors. Accordingly in the last decade, some guidelines have been established because of recent advancements in the field of oncological surgery, changes in chemotherapy regimens, and enhancements of radiological techniques.4

Adrenal surgery unlike adults, surgical resection is rec-ommended in pediatric cases because of the higher prev-alence of malignancy of adrenal masses. While open surgery was the most prevalent treatment modality in all the cases initially, a minimally invasive method, laparo-scopic adrenal surgery, has gained favorable recognition recently. Regardless of whether it is an open or minimally invasive procedure, adrenal surgery warrants expertise and accrued knowledge.

This study aims to retrospectively evaluate the role of imaging, surgical treatment and outcome in pediatric cases with adrenal masses.

2. Materials and methods

2.1. Study design and subjects

In this study, we retrospectively reviewed the medical re-cords of patients who underwent surgery for adrenal mass from 2007 to 2017 in our institution. The Local Ethics Board approved the study protocol. As patients were reviewed for age, sex, symptoms on admission, primary diagnosis,

diagnostic methods, radiological characteristics of the mass, surgical method for treatment, complications, dura-tion of hospital stay, and follow-up. In addidura-tion, the diag-nosis and treatment processes were assessed by a consensus group comprising pediatric surgery, radiology, and pediatric oncology, and pathology teams. Furthermore, when required, pediatric endocrinology consultations were performed in some patients.

2.2. Radiological evaluation

At the first visit, ultrasonography was used to localize and characterize the mass. In addition, magnetic resonance and computed tomography were performed to detect the presence of the vascular invasion and local and distant metastases.

2.2.1. Image-defined risk factors evaluation

Since 2010, the tumor localization, its relationship with surrounding organs and structures, and the infiltration characteristics were assessed for each case individually by the image-defined risk factors (IDRF) pediatric radiology team (Table 1). In patients aged <6 months with a cystic adrenal mass, normal neuron-specific enolase (NSE) and urine vanillylmandelic acid (VMA) levels, unilateral mass, restricted to the adrenal gland, not passing the midline without vascular invasion, and<16 mL in size, performing monthly follow-ups was decided with the assessment of NSE and VMA levels and Ultrasonography (US) imaging if consent was provided by the family and approved by the Pediatric Oncology Council. Later, surgical interventions were per-formed in cases of an increase in the mass size or VMA and NSE levels. Furthermore, surgical intervention was per-formed following the IDRF evaluation on patients aged>6 months.

Primary surgery was performed on patients with pheo-chromocytoma after the radiological and scintigraphic evaluation followed by the measurement of catecholamines and their metabolites’ levels in the plasma and urine and after decreasing the high blood pressure into normal ranges with the 3-week oral treatment. In addition, surgical intervention was performed if the solid masses were<5 cm in diameter with no invasion of the surrounding vascular structures. Of note, IDRF-negative cases with masses>5 cm

Table 1 Image-defined risk factors (According to Brisse et al3_).

Image-Defined Risk Factors

Adrenal tumor infiltrating the porta hepatis

Adrenal tumor infiltrating the branches of the superior mesenteric artery at the mesenteric root Adrenal tumor surrounding the origin of the celiac axis and the superior mesenteric artery Tumor invading one or both renal pedicles

Fusiform tumor surrounding the infrarenal aorta Tumor encasing the iliac vessels

Pelvic tumor crossing the sciatic notch

Tumor invading the branches of hypogastric vessels Dumbbell-abdominal

Other: Encasing vena cava

Neighboring organ infiltration: Diaphragm, kidneys, liver, pancreaticoduodenal block, mesentery

in diameter underwent direct surgical intervention following the IDRF evaluation. However, trucut biopsies were performed on IDRF-positive cases. In addition, com-plete excision or near-total excision was performed in cases confirmed as benign following the biopsy. Furthermore, chemotherapy was performed by the Pediatric Oncology Department in cases with malignant masses considering the histopathological results, stage, and prognostic criteria. Patients who underwent chemotherapy were evaluated using IDRF following neoadjuvant chemotherapy. Surgery was performed in IDRF-negative cases, and surgical inter-vention was performed following chemotherapy in IDRF-positive results.

2.2.2. Metaiodobenzylguanidine scintigraphy

Metaiodobenzylguanidine (MIBG) scintigraphy was per-formed in selected cases when the masses were solid and in

accordance with the tumor diagnosis, localization, and presence of metastatic disease.

2.3. Surgical intervention

In all the cases, surgical procedures were initiated for total resection, and near-total resection was performed in IDRF-positive cases with benign histological masses to avoid surgical mortality and morbidity. A laparoscopic trans-peritoneal approach was preferred for localized unilateral IDRF-negative masses of the adrenal gland. Notably, a standard 3-port technique was used in laparoscopy. How-ever, laparotomy was preferred for IDRF-positive post-chemotherapy patients. Fig. 1 summarizes the algorithm followed in the diagnosis and treatment. Furthermore, postoperative follow-ups were performed in conjunction with the Pediatric Oncology Department.

Figure 1 The surgical follow-up and treatment algorithm in adrenal mass cases. IDRF, image-defined risk factors; NSE, neuron-specific enolase; US, Ultrasonography.

Table 2 Characteristics of patients with adrenal mass. Number of cases 50 (M:27, F:23)

Mean age 4.8 years (5 dayse14 years) Initial symptoms Asymptomatic 17 (34%) Abdominal pain 15 (30%) Prenatal diagnosis 6 (12%) Abdominal mass 3 (6%) Virilization 3 (6%) Leg pain 3 (6%) Sweating 1 (2%) Orbital tumor 1 (2%)

Hypertension 1 (2%) Figure 2 Radiological diagnostic methods applied on cases. MRI, CT, US.

2.4. Statistical analysis

In this study, we used the chi-square test, independent-sample t-test, and paired t-test to perform the statistical analyses. We considered P< 0.05 as statistically significant. The SPSS 22.0 package program was used to perform the statistical analyses.

3. Results

In this study, we assessed 50 patients (27 males and 23 females; mean age, 4.8 years; range: 5 dayse14 years) who underwent adrenal mass surgery. In all, 34% of patients were asymptomatic and detected incidentally with USG, whereas 12% (6 cases) were diagnosed during the prenatal period. However, other cases (54%) presented with, at least, one symptom.Table 2summarizes the characteristics of the study cohort.

For radiological evaluation, US, Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) were per-formed in 42, 36, and 36 patients, respectively; both CT and MRI were performed in 24 patients (Fig. 2). In 25 patients, the mass localization was on the right side, whereas it was on the left side in 21 patients and bilateral in 4 patients. In addition, IDRF was positive in 17 patients and negative in 33 patients. At the time of the initial diagnosis, the mean volume measured radiologically was 36.5 (range: 0.68e668.9) cm3_{(Table 3).}

The pathological involvement was present in 15 of 23 patients who underwent MIBG scintigraphy, and bone scintigraphy was performed on 12 patients. In addition,

the trucut biopsy was performed in 13 cases involvement in 9 of 35 patients who underwent the bone marrow bi-opsy. In this study, histopathological findings were neu-roblastoma (n Z 29), ganglioneuroma (n Z 6), adrenal cortex tumor (n Z 5), ganglioneuroblastoma (n Z 4), pheochromocytoma (n Z 3), cyst (n Z 1), and adrenal hematoma (n Z 2; Table 4). Of note, 2 patients with pheochromocytoma underwent preoperative preparation using orala-blocker because of hypertension before pro-cedures. In addition, chemotherapy was prescribed to 14 IDRF-positive patients with neuroblastoma. Furthermore, open surgery was performed in 37 (74%) and adrenalec-tomy using laparoscopic methods in 13 (26%) patients as a surgical approach.

In the study cohort, the mean age of surgery was 8.2 months (range: 5 dayse3 years) in 6 patients diagnosed during the prenatal period. Indicators for surgery were suspected malignancy, an increase in the size during the follow-up period, and an increase in the NSE level. Of these, while 5 patients underwent open surgery, 1 patient underwent laparoscopy. The histopathological diagnosis was neuroblastoma in 4, hematoma in 1, and cyst in 1 pa-tient. The mean duration of laparoscopic surgery was 90.30 (range: 60e150) min. In this study, none of the patients who underwent open and laparoscopic surgery exhibited com-plications or required a blood transfusion. When decreased sizes of the masses after chemotherapy was evaluated preoperatively, the mean volumes were 13.88 (range: 0.96e49.14) cm3

for laparoscopy cases and 55.66 (range: 0.97e668.9) cm3

for open surgery cases; this difference was statistically significant (P< 0.05).

The assessment of 14 patients with neuroblastoma receiving preoperative chemotherapy because of IDRF positivity revealed that the average tumor size measured before chemotherapy was 175.55 cm3 _{and after}

chemo-therapy was 33.19 cm3; these changes in the volume of the masses were statistically significant (P< 0.05). In addition, the open surgery rate was 86%, and the laparoscopy rate was 14% in patients who underwent chemotherapy, whereas this rate was 31% and 69% in cases that did not receive chemotherapy. No statistically significant differ-ence was observed between the surgical methods and preoperative chemotherapy. The mean duration of the hospital stay was 3 (range: 2e6) days in the laparoscopy and 4.43 (range: 3e8) days in open surgery groups, which was statistically significant (P< 0.05). The mean follow-up time was 3.85 years (range: 2 monthse10 years). Of these cases, 2 patients were lost to follow-up, and 7 died because

Table 3 Radiological characteristics of adrenal masses. Localization of the lesion

Right 25

Left 21

Bilateral 4

Mean mass volume (cm3_{) 36.5 (0.68e668.9 cm}3₎

Density Solid 41 Cystic 4 Solid/Cystic 5 Vascular invasion 8 Irregular margins 9 Distant metastasis 13

Table 4 Characteristics of adrenal masses and surgical technique. Histolopathology Number

(n/%)

Hormonal activity (n)

Mean initial mass volume (cm3) Preoperative Chemotherapy (n) Surgical Technique Open Laparoscopic Neuroblastoma 29 (58%) 18 100.9 14 25 5 Ganglioneuroma/ Ganglioneuroblastoma 10 (20%) e 94.68 e 7 3

Adrenal cortex tumor 5 (10%) 3 28.70 e 2 3

Pheochromocytoma 3 (6%) 3 23.34 e 3 e

Adrenal cyst 2 (4%) e 1.81 e e 2

of progressive disease. Of those who died, 5 were diagnosed as stage 4, whereas 2 had stage 3 neuroblastoma.

4. Discussion

The most common adrenal masses in pediatric cases are neuroblastoma and pheochromocytoma of the adrenal gland originating from the neural crest. Neuroblastoma constitutes the leading extracranial solid tumor in pediatric cases and is accountable for 15% of tumor-related deaths. Neuroblastoma originating from the adrenal gland might encase or invade neighboring organs, vascular structures, and nerves. Previously, risk classification had been per-formed according to surgical and histopathological features after tumor resection; however, recently, the risk groups are determined according to the radiological characteris-tics of the diagnosis (IDRF).5The presence of, at least, one of these risk factors amplifies the complication rate intra-operatively and may lead to incomplete resection. Hence, neoadjuvant chemotherapy is recommended in the pres-ence of IDRF. Avanzini et al6reported that 30% of neuro-blastoma cases considered ineligible for resection initially became eligible after changing the method of evaluation. In this study, 5 of 6 patients (83%) diagnosed with neuro-blastoma and positive IDRF underwent surgery for the resection following neoadjuvant chemotherapy and re-ported no complications since.

Pheochromocytoma, another type of adrenal mass, oc-curs sporadically in children; however, the rate of familial predisposition and bilateral involvement is higher than that of adults. Open or minimally invasive methods might be preferred surgical techniques. Compared with other adre-nal pathologies, the rate of open surgery during laparos-copy is reportedly high.7,8_{In this study, a transperitoneal} approach was preferred in 3 patients with pheochromocy-toma because of the presence of bilateral lesions; while one of these patients underwent bilateral adrenalectomy owing to suspected malignancy, 2 were treated with adrenal-sparing surgery. In addition, adenoma, carcinoma, and cysts of the adrenal gland are unlikely observed in pediatric cases. Reportedly, carcinoma of the adrenal cor-tex in children often constitutes hormone-active tu-mors,9,10_{warranting caution to avoid rupture and bleeding} during surgical excision. Thus, open surgery is usually preferred in such cases. In this study, 2 of 4 adrenocortical tumors were removed with open surgery, whereas 2 were removed with a laparoscopic approach, and no complica-tions have been reported since then.

To date, no consensus has been attained on the tech-nique to be applied for the removal of adrenal masses. Because The open/transperitoneal approach offers a large study area, facilitates access to the adrenal space and perioperative sites, and enables the easier lymph node sampling, it is preferred.4,11However, a large incision site causes postoperative pain and extends the hospital stay. Thus, minimally invasive surgery is reported to be safe in IDRF-negative patients with tumors<5 cm in size. However, some studies have reported that the tumor size is not essential when selecting the surgical procedure and that the presence of vascular invasion is the only contraindica-tion to minimally invasive techniques. In a multicenter

study, Fascetti-Leon et al12_{reported that draining masses} up to 6.5 cm (145.6 cm3) could be reliably removed by the laparoscopic approach.12Reportedly, laparoscopy could be performed safely if IDRFs are regressed in the reassessment after chemotherapy, even in patients who were initially eligible for surgical resection.13,14

In this study, a marked difference was observed in the tumor size between the laparoscopy and open surgery groups. However, the literature reveals the mean tumor size of laparoscopic surgery cases to be smaller than open surgery. Our approach is in the direction of open surgery for IDRF-positive cases, even if IDRFs following chemotherapy are declining, because the laparoscopic technique has been applied in a small number of cases in the last 10 years, and lymph node dissection, especially in high-stage tumors, is easier to apply in open surgery. Furthermore, the presence of bilateral pheochromocytoma in this study led us to pre-fer the open surgical approach in these cases. However, as clinical experience increases, laparoscopic techniques are anticipated to be applied in patients including risk groups such as those with adrenal cortex tumors.

Some studies have reported laparoscopic adrenalectomy to cause less postoperative pain, have shorter operative time as experience increases, and shorter hospital stay compared with open surgery.15 Similarly, the duration of hospitalization was found to be shorter in our cases with laparoscopic adrenalectomy, which supported these data with an increase in the number of cases. Previously, some studies investigated the follow-up and treatment of adrenal masses detected during the prenatal period. Neuroblas-toma undergoes spontaneous regression under 1 year of age. Thus, a closer, nonoperative follow-up is recom-mended in patients aged <3 months, with tumors not crossing the midline, limited to the adrenal gland, and without vascular invasion.11,16_{However, if there is a change} in the lesion size and an increase in NSE values during the follow-up, surgical excision is recommended. In this study, surgical excision was required during the follow-up period in 6 patients with prenatal diagnosis; while 4 (66%) of these had poorly differentiated neuroblastoma, the masses were in a benign stage in the remaining 2 patients. In our clinical approach, owing to the risk of malignancy, adrenal masses diagnosed prenatally should be carefully followed in accordance with the literature.

This study has some limitations. First, the number of patients who underwent laparoscopic adrenalectomy is low in this study. Thus, a complete comparison with open sur-gery was not possible. Additionally the use of IDRF’s have not been defined in non-neuroblastic tumors however our initial clinical impression is that it can be useful in preop-erative evaluation and surgical planning in adrenal masses of children.

5. Conclusion

The crucial factors determining the surgical approach to adrenal masses in pediatric cases are the histopathology of the mass, volume, and its relationship with neighboring vascular structures. In neuroblastic tumors the evolution of treatment strategies over the last decade has become dependent on meticulous assessment of IDRF’s. Thus, the

preoperative radiological evaluation should be performed carefully, and the treatment plan should be established using a multidisciplinary approach. Overall, this study sug-gests that minimally invasive procedures are reliable in pediatric cases with adrenal masses.

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this article.

Funding

The authors have no funding to report.

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