JPED Journal

Introduction

Pheochromocytoma is a rare tumor arising from the chromaffin neuroendrocine cells located in the adrenal gland’s medulla and in other sympathetic nervous system ganglia. According to the WHO classification, pheochromocytomas (80%) originate in the adrenal medulla, while extra-adrenal masses, that can be located in different parts of the body, like abdomen, thorax, pelvis, and neck, are defined paragangliomas (20%). Pheochromocytoma produces and secretes catecholamines (epinephrine, norepinephrine, dopamine) [1]. The annual incidence is reported to be about 1 in 300,000 worldwide, and 20% of all these tumors are diagnosed in childhood and adolescence. . In children diagnosed with blood hypertension up to 1.7% have a catecholamine secreting neoplasm [2]. Pheochromocytoma and paragangliomas may be sporadic masses or involved in the context of an hereditary syndrome. Therefore, all patients diagnosticated with a pheochromocytoma should undergo genetic testing, that guarantee useful informations that can be valuable in screening, diagnosis, and prognostication of hereditary pheochromocytoma [3]. In children, the mean age of onset is among 11 and 13 years with a male preponderance of 2:1 [4-5]. The symptoms can be caused either by catecholamines overproduction, local pressure of the mass or metastasis presence [6]. Typical symptoms of catecholamine excess include diaphoresis, headaches, and palpitations. A long-standing hypertension may precipitate organs damage in heart, kidney, eyes, and central nervous system and deregulate glucose metabolism causing diabetes [7]. Therefore, prompt diagnosis is required, through clinical features, blood and urine exams, and radiological images.

The gold standard for treatment remains surgical resection. Surgical manipulation of tumor can lead to a massive release of catecholamines into circulation and may cause hypertensive crisis, cardiac arrhythmias, myocardial ischemia, pulmonary edema, and stroke. So, perioperative antihypertensive therapy is mandatory to avoid hypertensive peaks during anesthetic induction and surgical procedure and to prevent postoperative hypotension after tumor resection. Preoperative preparation is the same as with adults: adequate pre-operative α-adrenergic receptor blockers has been proven to reduce perioperative complications to less than 3% [8]. since they prevent intraoperative hemodynamic instability during mass resection; β-adrenoceptor blockers may be used for preoperative control of tachyarrhythmias or angina. However, loss of β-adrenoceptor-mediated vasodilatation in a patient with unopposed catecholamine-induced vasoconstriction can result in dangerous hypertension. Therefore, an α-adrenergic receptor blocker, that mediates vasoconstriction, should always be administered before employing β-adrenoceptor blockers [9].

Recent progresses in minimally invasive surgery are improving the feasibility and safety of laparoscopic adrenalectomy for non-malignant tumours, and it seems to reduce the “catecholamines storm” during operation. Also in pediatric surgery, laparoscopic approach finds wide application.

In particular, laparoscopic adrenalectomy has been accepted as the “gold standard” treatment modality for small-sized (<6 cm) pheochromocytomas and has been used for resection of largesized (>6 cm) masses [10].

We report a case of laparoscopic adrenalectomy in an 11-year-old patient with pheochromocytoma.

Case report

An 11-year-old boy attended the Ferrara University Hospital Pediatric Emergency Room, because of a long-lasting frontal headache associated with blood pressure values > 99^th percentile for age. In ER, blood pressure was measured at intervals of about 5-10 minutes with an automatic cuff: mean systolic blood pressure was 151-160 and mean diastolic blood pressure was 105-117 mmHg. Blood analysis showed normal blood counts, normal kidney and liver function, CK-MB and Troponin I was in range of normality. ECG also showed regular parameters. The 24h-urine analysis, revealed elevated levels of norepinephrine (996.83 μg/24h). Serum levels of aldosterone, cortisol, parathyroid hormone, ACTH, calcitonin, and renin were normal.

Abdominal ultrasound revealed the presence of a 35x40x50 mm solid mass in the left adrenal site. Therefore, a CT-scan was performed.  The mass presented inhomogeneous enhancement in arteriovenous phase, with a large central necrotic area, in close contiguity with the spleen and the upper pole of the left kidney. Kidney infiltration was suspected. Adrenal vessels were hypertrophic (Figure 1a and b).

Figure 1: Patient CT-scan showing the mass location and the anatomic infiltration (a) 3D reconstruction of adrenal vessels infiltration (b) Adrenal pheochromocytoma was the first diagnostic hypothesis.

During hospitalization, the patient underwent different clinical exams: genetic investigation, which didn’t highlight mutations in RET gene; ophthalmology consultation, normal; cardiological consultation, that confirmed hypertension associated to mild dilatation of the aortic root and right coronary tree, and outlined anti-hypertension therapy. The patients was referred to our Pediatric Surgery Unit. Doxazosin was administered at a starting dose of 1 mg / day (0.02 mg/kg), then increased up to 5 mg/day to normalize blood pressure before surgery. We decided to perform left laparoscopic adrenalectomy after 20 days of therapy, when blood pressure normalized. The patient has been placed in lateral decubitus with left side up (Figure 2).

Figure 2: Patient intraoperative position: right lateral decubitus with suspended arms, extended left leg and flexed right leg. The left side is exposed and the landmarks are tracked.

The surgery was performed under general anesthesia. The patient was intubated in supine position, and the anesthesiologist carried out rectus muscle nerve local block for better post-operative pain control. An urinary catheter and an adequate venous access were placed. Constant monitoring of vital signs, including blood pressure, oxygen saturation and ECG misuration, were performed throughout the surgery. Blood pressure was stabilized throughout the procedure by Urapidil Hydrochloride administration. Pneumoperitoneum was achieved through a 5 mm trocar, placed in the middle of a transverse line crossing the 11-th rib. Under direct vision, two 5 mm trocars were positioned on the midline, one at 10 cm from the xiphoid bones and the other on the left side, in order to obtain a correct triangulation of the left adrenal site. Then mobilization of the splenic flexure, splenorenal ligament and peritoneal fixation between the spleen and abdominal wall was performed with Thunderbeat® forceps. The Gerota’s fascia was incised with 5 mm Ligasure®. Once the mass was identified, no infiltration of the renal parenchyma was highlighted, the inferior adrenal vein (about 6-7 mm diameter) was isolated. Additional 5 mm and 12 mm trocars were helpful in the management of the central adrenal vein.  The vein ligation was performed by Medium-Large clips placed with Weck Hem-o-lok ® system (Figure 3 a and b).

Figure 3 : Intraoperative findings: (a) hypertrophic inferior adrenal vein (b) and his ligation by Hem-o-lok clips

The lesion was completely removed and placed in a 10 mm endo bag, then extracted by a Pfannenstiel incision. The mobilized spleen was fixed with interrupted suture to the parietal peritoneum. The operation time was about 240 minutes. Macroscopic appearance was of a 6 x 3.5 x 4 cm solid, capsulated, yellow ocher nodular lesion. Neither pressure and hemodynamic decompensations occurred during the procedure. Histological examination confirmed an high cellularity phaeochromocytoma, with marked cellular pleomorphism, quietly vascularized, with focal areas of necrosis. The proliferative activity index evaluated with Ki67 was approximately 3%. Phenotypic characterization: chromogranin +. synaptophysin +, S100 + (sustentacular cells), CAM5.2-, INIB-. The patient was admitted to intensive care for 48 hours. The postoperative period was uneventful. Blood pressure was normal during the hospital stay, without any antihypertensive treatment. Follow-up after the hospital discharge was performed by the Pediatric Oncohematologic Unit. PET-CT, performed three months after surgery, showed no disease reactivation.

Discussion

Pheochromocytoma is a rare type of neoplasm in childhood and it is responsible for 1% of cases of secondary hypertension. The incidence of malignant pheochromocytoma is about 0.02 cases per million [11]. In literature, it’s reported that the presence of a sporadic lesion and a tumor diameter larger than 6 cm are statistically significant for malignancy [12-13].

Patients with benign lesions are considered healed after surgical resection. In particular, symptoms related to catecholamine excess disappear. Laparotomic access was the gold standard until 1992 when Gagner et al. reported the first laparoscopic adrenalectomy in an adult man [14]. Overtime, laparoscopic transperitoneal technique has gained popularity also in pediatric centers.  Because of the low incidence of this neoplasm in childhood, we just found few pediatric cases in literature [15-17].

The development of multicenter retrospective studies could better delineate, in the future, the feasibility and safety of the laparoscopic technique in pediatric population [18,19]. shows the most important studies with stronger evidence in literature (Table 1).