Original article
Endoscopic treatment of large primary adrenal tumours
M. K. Walz1, S. Petersenn3, J. A. Koch2, K. Mann3, H. P. H. Neumann5 and K. W. Schmid4
Department of Surgery and Centre of Minimally Invasive Surgery and 2 Department of Radiology, Kliniken Essen-Mitte, and 3Department of Endorinology and 4Institute of Pathology, University of Duisburg-Essen, Essen, and $Medical Department IV, University of Freiburg, Freiburg, Germany
Correspondence to: Professor M. K. Walz, Department of Surgery and Centre of Minimally Invasive Surgery, Kliniken Essen-Mitte, Henricistrasse 92, D-45136 Essen, Germany (e-mail: mkwalz@kliniken-essen-mitte.de)
Background: Endoscopic adrenalectomy has become the treatment of choice for small benign adrenal tumours but should not be used for malignant lesions. It is debatable whether large and therefore potentially malignant primary adrenal tumours should be removed by minimally invasive techniques. Methods: Three hundred and eighty primary adrenal tumours in 368 patients (142 male and 226 female; mean(s.d.) age 48.9(14.4) years) were excised by laparoscopic or retroperitoneoscopic adrenalectomy. Adrenal neoplasias exceeded 6 cm in diameter (range 6-13 cm) in 33 patients (18 male and 15 female; age 42-6(14.2) years).
Results: There were no deaths. Patients with large tumours had an increased conversion rate (P = 0-039), longer operating time (P < 0.001) and greater intraoperative blood loss (P = 0.007) than those with smaller lesions, but a similar overall morbidity rate (P = 0-207). Six malignant tumours were identified (diameter 4-10 cm; four phaeochromocytomas and two adrenocortical carcinomas). Local recurrence developed in two patients and distant metastasis occurred in all six patients with malignant lesions.
Conclusion: Endocopic adrenalectomy perfomed by an experienced surgeon should be the treatment of choice for tumours exceeding 6 cm in diameter.
Presented in part to the First Congress of the European Society of Endocrine Surgeons, Pisa, Italy, May 2004
Paper accepted 19 January 2005 Published online 26 April 2005 in Wiley InterScience (www.bjs.co.uk). DOI: 10.1002/bjs.4964
Introduction
Laparoscopic adrenalectomy and retroperitoneoscopic adrenalectomy have become standard procedures. Both are recommended for the removal of benign adrenal tumours and adrenal hyperplasias, but should not be used if the primary lesion is known to be malignant. It is uncertain whether endoscopic techniques are appro- priate for potentially malignant adrenal masses, that is tumours with a diameter of 6 cm or more1-6. The present authors initially restricted endoscopic adrenalec- tomy to small tumours7, but have now expanded the indication to large adrenal masses after appropriate descriptions by others8. This paper describes an expe- rience with 33 endoscopic adrenalectomies for large primary adrenal tumours selected from a prospec- tive series of 429 minimally invasive adrenal opera- tions.
Patients and methods
Four hundred and fifty adrenalectomies were carried out in 415 patients (166 male and 249 female) between July 1994 and April 2004. Operations were performed at the Univer- sity Hospital of Essen (149 procedures) until August 1999 and at the Kliniken Essen-Mitte thereafter (301). Twenty- one open operations were performed (18 transabdominal and three retroperitoneal) and 429 endoscopic procedures. The latter group included 368 patients (142 male and 226 female; mean(s.d.) age 48.9(14.4) (range 10-80) years) with 380 primary adrenal tumours. Twenty-five of these tumours were removed laparoscopically and 355 by the posterior retroperitoneoscopic technique. Thirty-three of the 368 patients had primary adrenal neoplasias measur- ing 6 cm or more in diameter (Table 1). Twelve patients had bilateral adrenal tumours (11 phaeochromocytomas and one with Conn’s syndrome), which were removed by
the retroperitoneoscopic (20 tumours) or the laparoscopic (four) route. Five of these 12 patients, all with phaeochro- mocytomas, had a large tumour on one side and a small contralateral lesion.
Indications for endoscopic (laparoscopic or retroperi- toneoscopic) adrenalectomy included hormonally active tumours, non-functioning tumours with a diameter of at least 4 cm and lesions with proven growth. Endoscopic surgery was ruled out if there were radiological signs of malignancy, such as infiltration of neighbouring structures. The laparoscopic approach was used in obese patients (body mass index 45 kg/m2 or more), for tumours larger than 7 cm in diameter, or if synchronous laparoscopic surgery (such as cholecystectomy, hernia repair, excision of paragangliomas) was planned. Otherwise the posterior retroperitoneoscopic technique was used. Twenty patients with adrenocorticotrophic hormone-dependent bilateral hyperplasia and nine with secondary adrenal tumours were excluded from the study. All patients gave informed con- sent.
The posterior retroperitoneoscopic approach has been described in detail elsewhere9,10. The patient was placed in the prone position and the gas pressure was 20-24 mmHg. Initial mobilization of the upper pole of the kidney ensured early dissection of the main adrenal vein. The mobilized adrenal gland was placed in a retrieval bag and pulled
| All patients | Large tumours (≥ 6 cm) | Small tumours (< 6 cm) | |
|---|---|---|---|
| No. of patients | 368 | 33 | 340 |
| Sex ratio (M : F) | 142:226 | 18:15 | 128:212 |
| Age (years)* | 48.9(14.4) | 42.6(14.2) | 50-2(14.4) |
| Adrenal tumours | 380 | 33 | 347 |
| Conn's syndrome | 119 | 0 | 119 |
| Phaeochromocytoma | 104 | 20+ | 84 |
| Cushing's adenoma | 86 | 4§ | 82 |
| Virilizing tumour | 6 | 0 | 6 |
| Non-functioning tumour | 65 | 9 | 56 |
| Tumour size (cm)* | 2.9(1.9) | 7.3(2.1) | 2.5(1-2) |
| Tumour site | |||
| Right | 178 | 22 | 156 |
| Left | 202 | 11 | 191 |
| Surgical approach | |||
| Laparoscopy | 25 | 9 | 16 |
| Retroperitoneoscopy | 355 | 24 | 331 |
| Operating time (min)* | 80(49) | 110(63)] | 76(41) |
| Blood loss (ml)* | 42(111) | 141(285) ** | 29(55) |
*Values are mean(s.d.). Twelve patients had bilateral tumours (11 phaeochromocytomas, one with Conn’s syndrome); five patients with bilateral phaeochromocytomas had a unilateral mass of 6 cm or more in size. Three and one malignant; §two adrenocortical carcinomas. qP < 0.001, ** P = 0.007 versus small tumours (Mann-Whitney U test).
| All tumours (n =380) | Large tumours (n = 33) | Small tumours (n = 347) | |
|---|---|---|---|
| Intraoperative | |||
| Conversion to open procedure | 4 | 2* | 2 |
| Pleural tear | 4 | 0 | 4 |
| Hypertension (systolic | 5 | 1 | 4 |
| pressure ≥ 200 mmHg) | |||
| Blood loss (>500 ml) | 7 | 4+ | 3 |
| Death | 0 | 0 | 0 |
| Postoperative | |||
| Myocardial infarction | 1 | 0 | 1 |
| Myocardial insufficiency | 1 | 0 | 1 |
| Addisonian crisis | 1 | 0 | 1 |
| Pneumonia | 1 | 0 | 1 |
| Pneumothorax | 1 | 0 | 1 |
| Bleeding (> 500 ml in drainage) | 3 | 0 | 3 |
| Relaxation of abdominal wall | 26 | 2 | 24 |
| (temporary) | |||
| Hypaesthesia of abdominal wall | 9 | 1 | 8 |
| (temporary) | |||
| Incisional hernia | 1 | 0 | 1 |
*P = 0.039, +P = 0-002 versus small tumours (Fisher’s exact test).
through one of the subcostal incisions. The laparoscopic technique, with the patient in the lateral decubitus position, has been described previously by Gagner et al.11
Long-term results were collected by follow-up at the clinic or by contacting patients, their general practitioners and, in most cases, their endocrinologists by telephone.
Statistical analysis
Mann-Whitney U test and Fisher’s exact test were used for comparison between groups. P < 0-050 was considered statistically significant. Statistical analyses were performed using StatView® 5.0 (Abacus Concepts, Berkeley, California, USA).
Results
Intraoperative and postoperative complications associated with the 380 endoscopic adrenalectomies for primary adrenal tumours are listed in Table 2. There were no deaths. Patients with large neoplasias had an increased conversion rate (P = 0-039) and a greater intraoperative blood loss (P = 0.007) than those with smaller tumours, but the overall morbidity rate was similar (P = 0-207). An intraoperative blood loss of more than 500 ml was more common in those with large tumours (P = 0.002). No patient required a blood transfusion. The operating
300
240
Operating time (min)
180
120
60
0
Time
a Large tumours
300
240
Operating time (min)
180
120
60
0
Time
b Small tumours
time differed significantly for resection of small versus large tumours (P < 0.001). A learning curve was evident in both groups (Fig. 1); there was a reduction in operating time for endoscopically completed operations between the first and second halves of the study from a mean(s.d.) of 93(45) to 59(29) min for small tumours (P < 0-001) and from 135(52) to 93(67) min for large tumours (P = 0.004).
Histological examination confirmed that 374 tumours were benign and six were malignant. Overall mean(s.d.)
tumour size was 2.9(1.9) cm. Five of the malignant tumours were 6 cm or more in diameter. Local recurrence developed in two patients, including one who had potentially curative surgery. Distant metastases were diagnosed in all patients with malignant adrenal tumours. During mean(s.d.) follow- up of 51(32) (range 9-125) months for all patients with primary adrenal tumours, five of six patients with malignant adrenal masses died from widespread recurrence. During follow-up, one further patient died from cardiac arrest and six others from metastasizing bronchial carcinoma.
Discussion
Endoscopic adrenalectomy has become a ‘gold standard’ procedure, even though there has been no prospective randomized trial comparing the conventional open approach with the laparoscopic or retroperitoneoscopic method. However, a number of retrospective studies have clearly demonstrated the advantages of the endoscopic approach with respect to postoperative pain, blood loss and length of hospital stay4,7,12-17. Minimally invasive adrenalectomy is recommended for benign tumours, and contraindications mainly relate to malignant adrenal masses. The central problem in deciding the surgical approach is the preoperative identification of malignant neoplasias.
The present study demonstrated the feasibility and safety, in terms of short operating time, low intraoperative blood loss and low conversion rate, of endoscopic adrenalectomy even for adrenal tumours exceeding 6 cm in diameter. Similar results have been reported by Henry et al.1, who reported no perioperative morbidity after removal of 19 large tumours by the lateral laparoscopic approach. However, it should be noted that the excellent results in both series were largely based on daily experience in endoscopic surgery.
In the present series, five of six malignant tumours were larger than 6 cm in diameter. Although potentially curative surgery was undertaken in four of the six patients (one with adrenocortical carcinoma, three with malignant phaeochromocytomas), one developed local recurrence and all four developed distant metastases. Both local and distant metastases were evident within a few months after operation in the patient with cortical carcinoma, whereas metastases occurred after more than 3 years in the three patients with malignant phaeochromocytomas. It remains uncertain whether such neoplasias would have developed after a conventional open procedure. Local or locoregional recurrence has been described after conventional surgical resection of primary adrenocortical cancer18,19 and malignant or even benign phaeochromocytoma20,21. Although there are reports describing recurrence in the former location of the adrenal tumour and peritoneal seeding following minimally invasive adrenalectomy of primary adrenal tumors22-24, , it is still not known whether the frequency of such complications differs between conventional and endoscopic surgical procedures. As pointed out by Henry et al.1, the surgeon may use the endoscopic procedure as a diagnostic tool to identify potential malignancies. If dense adhesions and/or local fixation of the adrenal masses are found, conversion to open surgery should be chosen with a low threshold.
In large clinical series the rate of all malig- nant phaeochromocytoma ranges broadly from 3 to 29 per cent25-31. Indeed, the real incidence is unknown as there is no reliable method of accurately predicting the biological behaviour of these tumours. This is partly due to the problem of morphological diagnosis of adrenal tumours and limitations of presently available diagnostic tools including computed tomography and magnetic res- onance imaging. Such limitations preclude the accurate estimation of local or locoregional tumour control rates or recurrence rates. Furthermore, a tumour with the bio- logical ability to metastasize may never be recognized as malignant if it is resected before metastatic spread has taken place.
This study has demonstrated that endoscopic adrenalec- tomy can be carried out safely and successfully for primary adrenal gland tumours without radiological signs of malig- nancy, even if the tumour is large. Although the risk of malignancy increases with tumour size, the sensitivity of this variable is low and basically unreliable. The general strategy of excluding adrenal tumours with a diameter of 6 cm or more from endoscopic surgery should not be applied. However, advanced surgical experience and skills in endoscopic techniques are essential to a good outcome.
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