Is laparoscopic adrenalectomy feasible for adrenocortical carcinoma or metastasis?
FRANCESCO PORPIGLIA, CRISTIAN FIORI*, ROBERTO TARABUZZI, GIUSEPPE GIRAUDO+, CORRADO GARRONE+, MARIO MORINO+, DARIO FONTANA* and ROBERTO M. SCARPA
Division of Urology, Dipartimento di Scienze Cliniche e Biologiche, University of Turin, San Luigi Hospital, Orbassano, *Division of Urology II, and +Division of Surgery, Dipartimento di Discipline Medico-chirurgiche, University of Turin, San Giovanni Battista Hospital, Turin, Italy Accepted for publication 10 June 2004
OBJECTIVE
To review our experience with laparoscopic adrenalectomy (LA), to evaluate the effectiveness and safety of this procedure in patients with adrenal malignancy.
PATIENTS AND METHODS
The study included patients who underwent LA from 1995 to 2002, with histologically identified adrenocortical cancer (ACC) or metastasis. Indications for LA were adrenal masses with no radiological evidence of involvement of the surrounding structures, or solitary metastasis with well-controlled primary cancer. The variables evaluated were: size of the lesion, operative duration,
estimated blood loss, intraoperative complications, local, port-site and intra- abdominal recurrence, distant metastasis, and survival time.
RESULTS
Fourteen malignant adrenal lesions in 205 LAs (7%) were confirmed with histological diagnoses that showed a primary ACC in six and metastasis in another seven (in one there was bilateral metastasis). The mean (SD) size of the malignant lesions was 5.9 (2.8) cm. The 12 unilateral procedures required a mean operative duration of 164 (47) min; the bilateral procedure lasted 215 min. There was one conversion to open surgery caused by local infiltration, whereas there were no
intraoperative complications. The mean follow-up was 30 months, during which three patients died, one from endoperitoneal and trocar port-site seeding.
CONCLUSION
When the malignancy is confined to the adrenal gland, LA seems to be a feasible option if the principles of oncological surgery are respected. Nevertheless, further investigations are required to evaluate the appropriateness of this operation.
KEYWORDS
adrenal, laparoscopy, cancer, metastasis, adrenalectomy
INTRODUCTION
Minimally invasive techniques have modified the surgical approach to adrenal diseases and currently the indications for laparoscopic adrenalectomy (LA) include various pathological states, including functioning and non-functioning tumours, and rare entities such as cysts or myelolipomas [1-7]. Lesion size is no longer considered a definite contraindication, but LA may be not generally advisable for adrenal tumours of >12-13 cm because of the increased incidence of cancer [8,9]. Moreover, other limitations, e.g. bilateral lesions, previous surgery in the adrenal region or morbid obesity, are not considered a specific contraindication, but these limitations depend on the surgeon’s experience [5]. Many authors consider adrenocortical cancer (ACC) with local peri- adrenal invasion or venous thrombus the primary specific contraindication to this approach [3-5].
Whilst there is a general agreement and a plethora of papers about the use of LA, there
are few published reports on the results of LA for malignancy [2-9]. In the present study we review our experience with LA, to evaluate its effectiveness and safety in patients with primary ACC or in the presence of adrenal metastasis.
PATIENTS AND METHODS
We retrospectively reviewed the clinical and histopathological data of 205 patients who had LA from January 1995 to December 2002 at the authors’ institutions. Only patients with histologically primary ACC or adrenal metastasis were included in the study. The indications for LA were limited to patients with either functioning or non-functioning adrenal masses, with no radiological evidence of involvement of the surrounding structures, or with a solitary metastasis in the presence of a well-controlled primary cancer. For incidentalomas the indications for treatment were a lesion of ≥4 cm, heterogeneity on CT (Fig. 1) and increase in size during the follow-up.
All adrenal lesions were assessed before LA using CT and abdominal ultrasonography. MRI and positron emission tomography were used in selected cases, especially when the CT findings were unclear. All patients had a complete endocrinological assessment, which included plasma levels of adrenocorticotropic hormone, dehydroepiandrosterone sulphate, cortisol, mineralocorticoids, 17OH- progesterone and testosterone; and urinary levels of free cortisol, vanillylmandelic acid and catecholamine. Patients were informed in detail about LA, its risks and about the possibility of surgical conversion, and signed an informed consent.
All patients had transperitoneal LA, and were placed in the lateral decubitus position according to the procedure described previously [6] (Fig. 2); haemostasis was obtained exclusively using electrocoagulation and 11 mm clips for ligating vessels. Procedures were immediately converted to open surgery in cases where the lesion had signs of local invasion, and in LA the adrenal gland was extracted intact and
LAPAROSCOPIC ADRENALECTOMY FOR ADRENOCORTICAL CARCINOMA AND METASTASIS
placed in a sterile impermeable nylon bag.
The results were analysed using commercial statistical software, evaluating lesion size, operative duration, estimated blood loss, intraoperative complications, hospital stay and complications after surgery, local, port- site and intra-abdominal recurrence, distant metastasis, and survival time.
RESULTS
From 205 LAs there were 14 (7%) malignant lesions (ACC and adrenal metastasis) in 13 patients confirmed on histological examination (12 unilateral and one bilateral). The mean (range) age of the patients was 63.8 (47-81) years with similar numbers of men and women. The mean (SD, range) size of the lesions was 5.9 (2.8, 1.5-11) cm, with primary adrenal malignancies of 6.96 (2.79, 4.5-11) cm and adrenal metastases of 5.01 (2.77, 1.5-10) cm.
All lesions were ACC on histopathological examination, presenting as large (>4 cm) tumours and classified before LA as ‘incidentaloma. Before LA, CT showed no peri- adrenal invasion. All metastatic lesions were suspected before LA after evaluating the Houndsfield units (HU) on CT or by CT-guided fine-needle aspiration.
Four of the unilateral LAs were on the left and eight on the right; the mean operative duration (anaesthesia plus surgery) was 164 (47, 120-280) min. There was no significant difference in duration for left- or right-sided LAs; the bilateral LA took 215 min. The mean estimated intraoperative blood loss
A
B
C
D
1 2 3-4 5 6-7 8 9 ,9 1 12 13
| Diagnosis | No. of patients | Follow-up |
|---|---|---|
| ACC | 5 | 1 died from stroke at 15 months, 4 NED |
| Lung cancer metastasis | 2 | 1 died from endoperitoneal and port-site recurrence at 9 months, 1 NED |
| Renal cell cancer metastasis | 2 | 2 NED |
| Breast cancer metastasis | 1 | 1 died from thoracic recurrence at 23 months |
| Colon cancer metastasis (bilateral) | 1 | 1 NED |
| Leiomyosarcoma metastasis | 1 | 1 NED |
| Mixoid ACC | 1 | 1 NED |
| NED, no evidence of disease. |
was 400 ml for all the procedures. The histological diagnoses are reported in Table 1.
Conversion to open surgery was required in one patient with ACC because there was local infiltration; there were no complications during or after surgery. The mean hospital stay after LA was 4.9 (2.02, 3-9) days and the mean follow-up 30 (6-89) months, during which three patients died; one, who had primary cortical cancer, died from a stroke
and one, who had metastatic breast cancer, died from recurrent disease (thoracic invasion); the last patient, who had an adrenal metastasis from nonsmall cell lung carcinoma, died after 9 months of follow-up from endoperitoneal and trocar port-site seeding 5 months after the LA (Table 1). The seeding occurred initially on the right port site and the second seeding appeared at the point of specimen extraction. Subsequently, radiological evaluation using CT showed local
recurrence and endoperitoneal involvement (the seeding was confirmed by biopsy). During routine histological evaluation of the specimen there were positive margins along the cranial dissection in this patient, whilst all other specimens had no positive margins.
DISCUSSION
LA has become the reference standard in patients with adrenal lesions; several studies comparing LA with open adrenalectomy showed that LA was associated with less postoperative discomfort, decreased hospital stay, less disability, and either a lower or similar rate of complications [2-5,10-12]. In published studies it is suggested that there is only one contraindication for LA, the involvement of the surrounding tissue or of adrenal and caval veins by a malignant adrenal lesion (invasive adrenal carcinoma) [5], but there are few reports on LA for malignancy [5,13-17].
Suzuki et al. [18] used LA for a 4.5-cm left adrenal tumour; there was local recurrence in the adrenal bed, peritoneal dissemination at 19 months and patient died at 3 years. In another patient with a 5.5-cm left adrenal metastasis of pulmonary carcinoma, severe adhesions between the kidney and the adrenal gland required conversion to open surgery, and the patient died from metastatic disease after 8 months. Heniford et al. [19] reported a retrospective study of 11 patients with adrenal metastasis (10) and ACC (one); they concluded that LA for cancer is feasible and safe, but the short follow-up (mean 8.4 months) suggested that further study and appropriate follow-up are mandatory. Other cases are reported but the treatment of adrenal malignancy with laparoscopy is still controversial, because so few patients have been reported [13-16,20].
Thus we reviewed our series to provide further evidence and contribute to the discussion of LA for adrenal malignancy. From the 205 LAs, 13 patients had a histologically confirmed primary ACC or metastasis, with six primary ACC (five ACC and one mixoid ACC) and seven with secondary lesions. All primary ACCs were radiologically ≥4 cm and heterogeneous, and all were classified as adrenal incidentaloma. In all patients with secondary lesions the metastasis was detected on CT and specific
assessment by HU. The mixoid tumour is a rare entity with variable behaviour; in the present case immunohistochemistry showed aggressive features [21,22].
All patients with adrenal metastasis had primary stable disease and LA was indicated by the oncologist from published reports; such experience shows that treating an isolated adrenal metastasis from various primary neoplasms can improve the quality of life and perhaps survival time [23-25].
The mean size of the 14 malignant lesions was 5.9 cm, slightly larger than that reported previously (4.3 cm) which included all lesions [8]. These data confirm that malignant lesions are generally larger than benign ones.
The mean operative duration of 164 min (unilateral) and 215 min (bilateral) were long, because of technical difficulties, both for peri- adrenal tissue sclerotic reaction, the need for an accurate dissection to avoid violating the tumour capsule, and to respect the principles of oncological surgery.
The one conversion to open surgery was required for evident peri-adrenal infiltration, discovered during the laparoscopic dissection. The peri-adrenal extension of disease was not detected on CT before LA and the mass was then classified as an adrenal incidentaloma. The patient had an extended resection of the gland and of the peri-adrenal tissue. The histological examination confirmed ACC and the surgical margins were negative. After 22 months of follow-up the patient had no symptoms or signs of recurrent disease. In such cases it is mandatory to use an extensive dissection only possible by open surgery, to respect oncological surgical principles.
The present follow-up of 30 (6-89) months was insufficient to allow a definitive validation of laparoscopy for treating adrenal malignancy, but it was longer than most reported previously. There was one distant relapse and one local recurrence; in the former, the patient with breast cancer had a thoracic invasion, unrelated to LA, and in the latter (related to a lung cancer metastasis) there was port-site and massive endoperitoneal recurrence at 5 months. This lesion was considerably larger at LA than suspected on CT and previously several authors underlined the unreliability of imaging such as CT and MRI before surgery for detecting local invasion of tumours; our
experience confirms this. As such lesions can develop quickly it is important to use CT or MRI immediately before intervention to avoid having to treat unexpected large lesions or lesions with peri-adrenal involvement. Moreover, in this patient dissecting the peri- adrenal tissue was more difficult than usual. The cranial margins were particularly difficult to dissect, but despite that the LA was not converted, as we considered the dissection to be radical. The specimen was freed with no gross violation and removed intact, with no morcellation, in an entrapment sac. Notwithstanding the macroscopic appearance of the specimen, the histological analysis showed a positive margin. This partly explains the early recurrence of disease; rapid growth of the tumour and difficult dissection should be considered by the surgeon in such cases, and it is possible that the procedure should have been converted. The patient died 9 months after LA with no opportunity of initiating other therapies; other authors report similar experiences and suggest that LA for metastasis requires further investigation [20].
Thus LA appears to be a feasible option in patients adrenal malignancy, but when peri- adrenal infiltration is suspected during LA, or the principles of oncological surgery cannot be respected (i.e. tumour capsule violation), the procedure must be converted to open surgery. The present results partly confirm current research findings in this area, but as always it necessary to continue studies to further validate the appropriateness of this type of operation.
CONFLICT OF INTEREST
None declared.
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Correspondence: Francesco Porpiglia, Divisione Universitaria di Urologia, Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, Ospedale San Luigi, Regione Gonzole 10, 10043 Orbassano, Turin, Italy.
e-mail: porpiglia@libero.it
Abbreviations: LA, laparoscopic adrenalectomy; HU, Hounsfield units; ACC, adrenocortical cancer.