Study setting and timing
To investigate the three points defined in the introduction, a questionnaire was prepared by four authors (MM, BB, RP, AC) working at the “Federico II” University and e-mailed at the end of 2011 to surgical units with an experience of more than fifty laparoscopic adrenalectomy operating in the Campania Region, Italy. Seven surgeons from six centres participated in this audit: 2 university centres (1 from Naples Second University “SUN” and 1 from Naples “Federico II” University), and 3 regional hospitals with four centres. The duration of data analysis ranged from January 1993 to December 2011. During this period 506 laparoscopic adrenalectomies (LA) were performed on 498 patients. Male patients were 177 (35.5%). Mean age was 49.7 (range 16–78). In 282 cases, (55.7%) the resection was performed due to a preoperative diagnosis of adrenal incidentaloma. All six centres began, starting from 2001, a strict collaboration with the endocrinology unit of the “Federico II” University in terms of biochemical assessment, imaging evaluation and indication to surgery of detected incidental lesions.
Study design
The retrospective review of a prospectively collected database was conducted. The main parameters asked in the questionnaire defined:
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1.
The preoperative functional status and the dimensions of the lesions obtained by biochemical study, CT scan with or without contrast, MRI, radionuclide scanning (MIBG, FDG PET, PET-CT or NP-59) or eventually FNAB.
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2.
Indications to surgery
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3.
The surgical records in terms of operative time, number of ports used and intraoperative complications, eventually requiring conversion to open surgery.
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4.
The postoperative records in terms of duration of hospital stay, complications eventually requiring re-intervention, final dimension and histology of the specimen, and survival data for malignant lesions.
All data recorded later than 1999 were saved on electronic sheets under the supervision of the surgical units heads. Part of the data was collected manually before that period. All records, once returned, were then introduced in a database under the supervision of the authors of the questionnaire for computer processing. A data quality control was performed at that time.
According to study aim, patients were then classified and divided in two groups.
When preoperative diagnosis was “incidentaloma” (282/506 adrenalectomies), only 230/282 lesions (81.5%) underwent, at the time of diagnosis, both a biochemical and radiological investigation, performed by the same endocrinologists group, acting as coordinator. The study, according to guidelines [5], was aimed to:
Rule out subclinical cortisol secreting lesion by an overnight 1 mg dexamethasone suppression test. A response providing values lower than 5 μg/dL was considered normal.
Rule out any subclinical aldosterone secreting lesion by evaluating serum potassium and the plasma aldosterone concentration/plasma renin activity ratio. The cut-off was considered a plasma aldosterone concentration-plasma renin activity ratio greater than 30 and a plasma aldosterone concentration greater than 0.5 nmol/L (20 ng/dL).
Evaluate 24-hour total urinary metanephrines and fractionated catecholamines (or both plasma and urine study) to exclude a pheochromocytoma. A 24-hour urine total metanephrine level above 1,800 μg and a plasma metanephrine level exceeding 3 times normal were assumed diagnostic for a pheochromocytoma.
Conversely, once defined lesions smaller than 4 cm, with benign non contrast CT scan features, all non-functioning lesions looking indeterminate or malignant, were evaluated by using a contrast enhanced CT scan or alternatively in 38/230 cases by MRI. In 25/230 cases a PET-CT scan was however used due to the inconclusive response of CT scan [14]. An imaging pattern not fulfilling the CT scan criteria although suggestive of malignancy was defined indeterminate. The criteria used, indicating a primary ACC in non-functioning incidentalomas were [9, 15, 16]:
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An attenuation value higher than 10 HU on non contrast CT scan
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A contrast agent washout lesser than 50%
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Dimension bigger than 6 cm.
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Irregular shape, central necrotic areas, vena cava thrombosis.
Indication to surgery in this group of incidentally discovered lesions were then considered:
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Non functioning lesions larger than 4 cm (76 patients)
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Non functioning lesions smaller than 4 cm but increasing in radiographic dimensions or becoming hormonally active within the first year from diagnosis (75 patients)
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Monolateral aldosterone producing masses (18 patients)
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Hormonally active pheochromocytomas (22 patients)
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Patients younger than 40 presenting with a subclinical Cushing syndrome [17] of recent onset and accompanied by worsening of hypertension, abnormal glucose tolerance and osteoporosis (39 patients)
These patients studied and treated according to guidelines, were classified and included in group A.
The remaining 52/282 (18.5%) lesions were preoperatively studied elsewhere with incomplete imaging and underwent surgical resection without further biochemical testing. Most of them (49/52, 94.2%) were treated from 1993 to 2000, at the beginning of the laparoscopic adrenalectomy experience. Incomplete imaging means CT scan performed without contrast when requested or without measuring contrast washout kinetics [4, 5]. In these patients, classified as group B, MRI or nuclear scanning were never used. The lack of any clinical manifestation of endocrine activity in presence of an incidental adrenal lesion, evaluated as resectable at imaging, was considered a valid indication to surgery. They, according to the authors of the questionnaire, did not fulfill the preoperative study criteria requested to be included in group A.
All incidental lesions presenting an elevation of 24-hours urinary metanephrines and fractionated catecholamines in group A were treated with an α adrenergic blockade before resection. Subtotal adrenalectomies were not performed. Six patients (1.2%) were approached in supine transabdominal position. The posterior retroperitoneal approach was not used. The “Federico II” University ethical committee, which is the reference centre for our region, authorized the use of all data concerning this study. Before surgery, all patients signed an informed consent, requested by Italian laws and granted by our ethical committee, explaining in detail all the risks and the benefits provided by adrenalectomy.
Statistical analysis was performed with SPSS version 14.0 (SPSS©, Chicago, IL, USA). The Yates corrected χ2 test was used as a means of evaluating differences in category variables, and the independent sample test was used for continuous variables. Significance was assigned at a level of p <0.05.