Role of Laparoscopy in the Management of Adrenal Malignancies
CELESTINO PIO LOMBARDI, MD, MARCO RAFFAELLI, MD,* CARMELA DE CREA, MD, AND ROCCO BELLANTONE, MD Division of Endocrine Surgery, Department of Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
Background and Objectives: The role of laparoscopic approach for the treatment of malignant adrenal diseases is still controversial. The aim of this study was to verify the results of laparoscopic adrenalectomy (LA) in the management of adrenal malignancies.
Methods: The medical records of all the patients who underwent laparoscopic procedures for adrenal diseases and in whom malignancy was demonstrated at final histology were reviewed.
Results: Nine patients were included (three malignant pheochromocytomas, four adrenocortical carcinomas, and two adrenal metastases). At a mean follow-up of 23.0 months, all but two patients were alive. One patient died for metastatic disease and the other one for unrelated causes. One patient operated on for an adrenocortical carcinoma developed a pelvic recurrence. One patient operated on for a malignant pheochromocytoma developed multiple intra-abdominal recurrences. No other case of recurrence was observed.
Conclusions: The results of this study demonstrate that LA can have a role also in case of adrenal malignancies. Conversion to open surgery is mandatory in case of local invasion and when the dissection cannot be as accurate as in conventional operations. A preliminary laparoscopic exploration can be planned in case of suspected malignant lesions to confirm the diagnosis and to evaluate their operability.
J. Surg. Oncol. 2006;94:128-131. @ 2006 Wiley-Liss, Inc.
KEY WORDS: laparoscopic adrenalectomy; adrenal malignancy; adrenal cortical carcinoma; malignant pheochromocytoma; adrenal metastasis
INTRODUCTION
During the last decade laparoscopic adrenalectomy (LA) has become the new gold standard for the treatment of benign adrenal disorders, both functioning and non- functioning [1]. Indeed, early after its first description [2], several studies have documented its superiority over conventional open adrenalectomy (CA = conventional adrenalectomy), in terms of postoperative recovery, hospital stay, overall costs [3-7].
CA is still considered the approach of choice for invasive adrenal malignancies, since it provides an optimal exposure of intra-abdominal organs and vessels, allowing for a large, complete and oncologically correct en bloc resection, when feasible and necessary.
Laparoscopic removal of primary or secondary adrenal malignancies is still controversial [8-16]. The growing
experience with LA and the excellent results of this procedure have led several authors to propose it also for large and potentially malignant adrenal tumors [9,10] and for adrenal metastases [9,12-16]. However, the experience is still limited and no conclusive data are available.
In this study we retrospectively evaluated the series of patients who underwent LA in our Department and in whom malignancy was demonstrated at final histology,
*Correspondence to: Dr. Marco Raffaelli, Divisione di Endocrinochirurgia, Istituto di Clinica Chirurgica, Dipartimento di Scienze Chirurgiche, Università Cattolica del Sacro Cuore, L.go A. Gemelli 8, 00168 Rome, Italy. Fax: +39-06-30156579. E-mail: marcoraffaelli@rm.unicatt.it
Received 27 April 2004; Accepted 15 September 2004 DOI 10.1002/jso.20599
Published online in Wiley InterScience (www.interscience.wiley.com).
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with the aim to verify the role of laparoscopy in the management of adrenal malignancies.
MATERIALS AND METHODS
Seventy patients underwent laparoscopic procedures for adrenal diseases between January 1997 and June 2003.
Among them, patients in whom a primary or secondary adrenal malignancy was diagnosed at final histology were included in the study. The classification of “malignant” for pheochromocytomas was based on the histologic criteria (vascular and/or capsular invasion) and not upon the evidence of gross clinical/local invasion or the clinical behavior alone [17]. The medical records of this group of patients were reviewed.
The following parameters were registered: age, sex, preoperative diagnosis, preoperative diagnostic studies results (ultrasound, CT, and/or MR scan), laparoscopic approach, operative procedure, operative time, complica- tions, postoperative course, pathological findings.
In our Department LA has been performed since January 1997 by a trans-peritoneal flank approach, as described by Gagner et al. [18]. Since May 2003 we adopted also a posterior retroperitoneoscopic approach, as described by Walz et al. [19], especially for small (<6 cm) and/or bilateral adrenal tumors, and in patients with previous abdominal surgery.
Laparoscopic procedures included adrenalectomy and diagnostic laparoscopy. Follow-up was obtained by clinic follow-up visits and direct contact of the patients.
RESULTS
Nine patients satisfied the inclusion criteria. There were seven women and two men with a mean age of 48.7 ±21.2 years (range: 22-79). Preoperative diagnosis was: adrenal incidentaloma in four cases, pheochromo- cytoma in two, single adrenal metastasis in two, suspicion of adrenocortical carcinoma in one. Mean lesion size was 5.9 ± 2.4 cm (range: 2-10). Preoperative imaging studies (CT and/or MR scan) showed suspected malignant characteristics in four cases: two suspected metastases, one suspected adrenocortical carcinoma, and one sus- pected malignant pheochromocytoma. In these last two cases local invasion (infiltration of the left kidney and pancreas tail in one case and of the spleen in the other) was suspected. No patient underwent preoperative fine needle aspiration biopsy (FNAB).
In all the cases a laparoscopic trans-peritoneal flank approach was adopted. In seven patients adrenalectomy was accomplished laparoscopically.
Conversion to open procedure was required twice because of the evidence of large malignant tumors
necessitating a wide excision of adjacent infiltrated structures (adrenalectomy + nephrectomy +splenectomy + distal pancreatectomy in one case of adrenocortical carcinoma; adrenalectomy + splenectomy in one case of malignant pheochromocytoma). In these cases malignancy was suspected preoperatively and laparoscopic exploration was planned to evaluate the resectability of the lesion as first step of surgical procedure. In both cases laparoscopic exploration showed the resectability of the lesion even if necessitating large en bloc excisions. Laparoscopic explora- tion took 30 min in the patient with large adrenocortical carcinoma and 40 min in the patient with malignant pheochromocytoma. Conversion was performed by a flank subcostal incision in both cases.
Mean operative time was 195 ±51 min (range 120- 220). No complication occurred. Final histology showed: malignant pheochromocytoma in three cases (diagnosed only on the basis of histological criteria in two cases), adrenocortical carcinoma in four and adrenal metastases in two (from lung carcinoma in one case and breast carcinoma in the other one). Mean postoperative stay was 8.3 ±3.5 days (range: 5-15).
At a mean follow-up of 23.0±14.1 months (range: 8-41), all but two patients were alive. One patient operated on for adrenal metastases of non-small cells lung carcinoma died for metastatic disease 3 years after adrenalectomy. One patient, operated on for locally infiltrating adrenocortical carcinoma (adrenalectomy + nephrectomy + splenectomy + distal pancreatectomy) died for unrelated causes (hepatic failure due to cirrhosis).
One female patient with a 6-cm adrenocortical carcinoma which was removed laparoscopically without any evidence (macroscopic and microscopic) of capsular rupture and cell seeding, developed a pelvic recurrence, 18 cm in diameter, 6 months after surgery, while under mitotane treatment. She underwent eight cycles of multidrug chemotherapy (etoposide, doxorubicin, and cisplatin), with a good response (the maximum diameter of the pelvic mass after treatment is 3.0 cm). She is now under evaluation for a second surgical look, to remove the residual recurrent lesion.
A male patient with a history of familial pheochro- mocytoma, operated for a left 6.5 cm pheochromocytoma which was removed without any evidence (macroscopic and microscopic) of capsular rupture and cell seeding, with only histologic (microscopic) evidence of vascular invasion, but no gross evidence of malignancy, was reoperated 1 year after the first operation for multiple recurrences developed in the pedicle of the spleen, in the abdominal wall and in the omentum. He is now waiting for high-dose Iodine 131-meta-iodobenzylguanidine (131I-MIBG) treatment.
No other cases of local or port site recurrence or distant metastase has been registered.
DISCUSSION
Since no conclusive data exist in the literature, the role of laparoscopy in the treatment of adrenal malig- nancies is still controversial [8-10,12,13]. Indeed, if CA is still the approach of choice for invasive adrenal malignancies, providing good exposition, and safe oncological resection, also in case of extensive local invasion, it is often difficult to determine the malignant potential of adrenal neoplasm because there is no reliable preoperative diagnostic test. The size of adrenal neoplasm has been regarded by some investigators as the most important factor to predict the risk of malignancy for adrenal lesions [20]. This is the reason why at the beginning of the experience with LA, most centers have used adrenal tumor size of 5-6 cm or greater as a contraindication for laparoscopic resection because of the risk of malignancy [9,10]. It is unclear, however, at what size an adrenal neoplasm should be resected by means of an open approach or a laparoscopic approach. Despite the improvement of imaging studies during recent years (computed tomography, magnetic resonance imaging, MIBG, and 6-beta-iodomethyl 19-norcholes- terol I 131 scintiscan; PET scan), they are not accurate enough to diagnose or to preoperatively exclude primary adrenal cancers or metastasis. Given that no reliable and accurate preoperative diagnostic test to confirm the diagnosis of a primary malignant adrenal tumor or an adrenal metastasis exists, it is difficult to determine when an open approach should be used. In the cases in which the diagnosis of malignancy is not established before surgery we do not believe that LA is contraindicated. Computed tomography (CT) scan and CT angiography, as well as magnetic resonance (MR) imaging are recommended in the preoperative work-up of adrenal lesion to assess the presence of signs of malignancy or local invasion. However, an initial laparoscopic approach can be used to establish the diagnosis with low morbidity and allows curative resections in most instances. Moreover, in case of suspected extensive local invasion an initial laparoscopic exploration may be useful to evaluate the resectability of the lesion. Laparoscopy has been demonstrate to decrease the incidence of unnecessary laparotomy for unresectable disease in up to 67% of patients with abdominal malignancies [21] Obviously, in patients who have local invasion requiring adjacent organ resection, a laparo- scopic approach should be converted to CA. This situation occurred in two patients in this series, and a diagnosis of ACC and malignant pheochromocytoma was confirmed at final histology. Conversion should not be considered a defeat for the surgeon but a different way to accomplish the procedure respecting the principles of oncological resection.
As other authors [9-11], we have completely removed laparoscopically three other ACCs and two malignant pheochromocytomas without difficulty. There were no signs of local invasion during surgery, and the tumors were well encapsulated macroscopically. En bloc resec- tions were performed in all cases without any capsular disruption. Retrospectively, we believe that we would not have performed more extensive surgery through an open approach, even knowing that tumor was malignant.
Unfortunately, we observed two recurrences after LA for malignancies: a pelvic recurrence 6 months after the laparoscopic removal of an encapsulated adrenal cortical carcinoma and an intra-abdominal recurrence 1 year after the removal of an encapsulated malignant pheochromo- cytoma. In both cases there was no evidence of tumor capsular rupture or spillage of tumor cells.
This finding confirms those of other authors [9,22,23]. Anyway, one must keep in mind that recurrences are also observed after open adrenal surgery for stage I and II adrenocortical malignant tumors, and the reported rate of recurrence after LA for malignant disease are similar to those of open surgery [22]. Indeed, recurrence has been described in 0-50% of the cases in the different series after LA for ACC, while it is reported in up 70% of the cases following open adrenalectomy [23]. Recurrence after adrenalectomy for pheochromocytoma in the prelaparoscopic era was observed in 6-8% of patients [23].
On the other hand, some cases of local recurrence and intra-peritoneal tumor dissemination after LA for malig- nant lesions have been reported in the literature [24-27]. Recurrences may due to the incomplete resection or capsular disruption of the tumor during dissection. These intra-operative complications are also observed during open surgery. Nevertheless, it should be pointed out that surgeon training and experience play an extremely important role for a safe tumor dissection. Indeed, inadvertent tumor capsule disruption may result in intra-peritoneal or port-site recurrence.
Adrenal metastases commonly occur in patients with cancers of the lung, kidney, gastrointestinal tract, breast, and melanoma [28]. Rarely, patients may present with an isolated adrenal metastasis. Several investigators have documented that aggressive surgical resection of adrenal metastasis, when done in patients with solitary, resectable disease and after a long disease-free interval, can result in prolonged patients survival [28]. Thus, in recent years a trend towards a more aggressive approach for solitary adrenal metastases from non-adrenal cancer in selected patients has been proposed by several authors [12, 14-16,28]. The low invasiveness of LA renders it particularly suitable for oncologic patients and may induce the oncologists to be more prone to refer patients with single adrenal metastases to surgeons. Considering
Journal of Surgical Oncology DOI 10.1002/jso
the excellent compliance shown by these patients and the encouraging results obtained [14-16], this new indica- tion could represent a positive change produced by the introduction of LA. In our series LA for adrenal metastases confirmed the good results reported in the literature, without evidence of recurrence.
CONCLUSIONS
LA can be safe and effective also in case of primary and secondary adrenal malignancies. In experienced hands, LA can be proposed for large (>6 cm), potentially malignant adrenal tumors. Even if an open approach to allow en bloc resection would be preferable in patients who have ACC, LA could be suitable whenever the diagnosis is not certain preoperatively. Using only the criterion of adrenal tumor size too many patients would subject to an unnecessary open procedure. Conversion to open surgery is mandatory in case of local invasion and when the dissection cannot be as accurate and safe as in open surgery, respecting the principles of oncological surgery. A preliminary laparoscopic exploration can be planned in case of suspected malignant lesion to confirm the diagnosis and to evaluate its operability. At present the exact risk of intra-abdominal and parietal recurrence is unknown. However, a good surgical training and technique play a role of utmost importance.
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