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THE SURGEON JOURNAL OF THE PCYM. COLIFORM OF SLIMGIRONI OF SEINIKUPOH AND IRELANDI
Minimally invasive surgery for malignant adrenal tumors
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Antonio Toniato*
Surgical Pathology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy
ARTICLE INFO
Article history: Received 1 October 2012 Received in revised form 6 December 2012 Accepted 17 January 2013 Available online 13 February 2013
Keywords:
Adrenal tumors Malignancy Laparoscopy Surgery
ABSTRACT
Background: The increasingly widespread use of minimally invasive surgery has allowed surgeons to exploit this approach for malignant adrenal tumors, though its actual role remains debated. The purpose of this study was to ascertain whether minimally-invasive surgery is a safe and effective treatment for adrenal carcinoma and metastases.
Methods: Demographic and clinical data were prospectively entered in a computerized endocrine surgery registry for all patients who underwent surgery for adrenal lesions at our institution over a 20-year period (1991-2010). For the purposes of the present study, the registry was queried to identify patients who had minimally-invasive surgery for adreno- cortical carcinoma (group 1) or adrenal metastases (group 2).
Results: Out of 332 patients undergoing adrenalectomy 25 were operated on for adrenal malignancies: 9 (group 1) had primary adrenal carcinomas and 16 (group 2) had adrenal metastases. Successfully laparoscopic adrenalectomy was performed in 16.6% (1/6) and in 93.3% (14/15) of group 1 and group 2, respectively. The mean operating time was 140 min (range 70-280 min) and 80 min (range 50-180 min) for groups 1 and 2, respectively.
The median survival for group 1 was 30 months and Kaplan-Meier life table analysis showed a survival rate of 89%, 25.4% and 12.7% at 1, 3 and 5 years, respectively. The median survival for group 2 was 28 months and Kaplan-Meier life table analysis identified survival rates of 94%, 20.1% and 6.7% at 1, 3 and 5 years, respectively.
Conclusions: This study shows that laparoscopic resection is inappropriate for patients with known or suspected adrenocortical carcinoma, while the laparoscopic approach can be justified and is feasible in case of adrenal metastases.
@ 2013 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.
Introduction
In the last 20 years, minimally-invasive methods have radi- cally changed adrenal surgery, making access to the adrenal gland easier and less traumatic. Many studies have docu- mented that laparoscopic adrenalectomy can now be recom- mended for almost all adrenal masses because it offers lower
complication rates, less postoperative pain, shorter hospital stays, excellent cosmetic results, and other benefits.1-5
All these advantages have prompted interest in expanding laparoscopic adrenalectomy to the treatment of primary ad- renal tumors and adrenal metastases as well.6-9
Laparoscopic adrenalectomy for adrenal malignancies remains a highly controversial problem, however, because
* Corresponding author. Tel./fax: +39 049 821 2250. E-mail addresses: giorgiolina@libero.it, antonio.toniato@unipd.it.
1479-666X/$ - see front matter @ 2013 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.surge.2013.01.004
there is reported a risk of carcinomatosis or port site metastasis.10-12
The purpose of this study was to ascertain whether minimally-invasive surgery is a safe and effective treatment for adrenal carcinoma and metastases.
Material and methods
Demographic and clinical data were prospectively entered in a computerized endocrine surgery registry for all patients who underwent surgery for adrenal lesions at our institution over a 20-year period (1991-2010).
The study was conducted in compliance with the stan- dards of our local ethical committee.
For the purposes of the present study, the registry was queried to identify patients who had minimally-invasive surgery for adrenocortical carcinoma (group 1) or adrenal metastases (group 2).
All patients had undergone CT or MRI of the abdomen and chest, and many of them had also had FDG-PET, and they were all recommended for surgery after a collegial discussion with an endocrinologist and an oncologist.
Only patients in group 1 with no distant metastases and cases in group 2 with solitary adrenal metastases were refer- red for adrenalectomy.
Adrenocortical carcinomas were classified according to the European Network for the Study of Adrenal Tumors (ENSAT).13
All surgical procedures were performed by the same sur- geon, and laparoscopic access was via transperitoneal lateral approach.
All patients were followed up clinically by an experienced endocrinologist and an oncologist every 3 months during the first year and then every 6 months up to 5 years, then yearly thereafter. Postoperative surveillance included clinical ex- amination, CT or MRI scanning of the abdomen and chest, and blood tests to check for oncological markers. A PET scan was performed in some cases.
Statistical analysis: long-term survival rates were assessed using Kaplan-Meier analysis.
Results
Between 1991 and 2010, 332 patients underwent adrenalec- tomy at our institute, 122 for Conn’s disease, 109 for pheo- chromocytoma, 53 for Cushing’s disease, 52 for incidentaloma and 25 for malignancies.
The patients with adrenal malignancies included 14 males and 11 females, whose mean age was 61.2 years (range 54-87 years); 10 had a right mass and 15 a left one.
Nine patients (group 1) had primary adrenal carcinomas and 16 (group 2) had adrenal metastases.
The patients in group 1 had tumors ranging in size from 3.5 to 19 cm (mean 9.6 cm) and their adrenal mass was detected because the tumors were secreting a mild excess of cortisol in 6 cases, a combination of cortisol and aldosterone in another 2, and 1 case was nonfunctioning.
The mean overall operating time was 140 min (range 70-280 min).
Three patients had from initially open surgery because preoperative imaging studies clearly showed invasion of adjacent structures by large masses (10, 12 and 19 cm in size). The first patient underwent en-bloc resection of the adrenal gland, which was associated with splenectomy, the second with distal pancreatectomy and nephrectomy and the third underwent adrenalectomy with hepatic resection.
In the remaining six patients, surgery began via a laparo- scopic access, but the adrenalectomy was completed suc- cessfully in only one (16.6%). This patient had a preoperative diagnosis of incidentaloma 3.5 cm in size that was diagnosed as adrenal cancer only at histology. Conversion to open sur- gery was necessary in the other 5 cases due to technical problems making it inadvisable to continue the procedure laparoscopically. The reasons for the conversion were as fol- lows: the tumor was found to have malignant features as infiltration of surrounding structures (3 pts), para-tumor bleeding (1 pts) and technical reasons due to a large mass to achieve adequate resection of the margins of tumor (1 pts).
According to the ENSAT classification, one patient was in stage 1, three were in stage 2, and five were in stage 3.
In group 2, the adrenal masses were identified on follow-up radiological examinations for previous cancer. The size of the tumors was in the range of 2-8 cm (mean 3.2 cm). The patients had a history of renal cell carcinoma in 8 cases, lung cancer in 4, colorectal cancer in 2, breast cancer in 1, and seminoma in one. The mean operating time was 80 min (range 50-180 min). The intervention started in 15 patients by laparoscopic access and adrenalectomy was completed successfully in 14 patients in group 2 (93.3%). The procedure was converted to open sur- gery in one renal cell carcinoma patient with a metastatic mass 8 cm in size suspected of infiltrating the inferior vena cava. In the last patient, the sequelae of prior abdominal sur- gery (left nephrectomy) contraindicated laparoscopic access.
Overall morbidity was represented by anemia in two cases (one needing a blood transfusion), pneumonia in one and prolonged ileus in two.
There were no perioperative (30-day) deaths or major complications in any of the patients, and a long-term follow- up (mean 28.3 months, range 8-60 months) was obtained in all cases.
The results are summarized in Table 1.
The median survival for group 1 was 30 months and Kaplan-Meier life table analysis showed a survival rate of 89%
| Table 1 - Perioperative results. | |||
|---|---|---|---|
| Adrenocortical K | Adrenal metastases | Total | |
| Open surgery | 3ª | 1º | 4 |
| Laparoscopic access | 6 | 15b | 21 |
| Conversion to open | 5ª,c | 1 | 6 |
| Successful | 16.6% | 93.3% | 71.4% |
| laparoscopy | |||
| Death | 0 | 0 | |
| Morbidity. | |||
| a 2 cases anemia. | |||
| b 1 case pneumonia. c 2 case ileus. | |||
(SD ± 9.9), 25.4% (SD ± 7.2) and 12.7% (SD ± 8.4) at 1, 3 and 5 years, respectively. Seven patients died of locally recurrent disease and/or distant metastases, and one of them developed peritoneal carcinomatosis. Two patients (one in ENSAT stage 1 after a 60-month follow-up and another in stage 2 after a 12- month follow-up) are alive and disease-free.
The median survival for group 2 was 28 months and Kaplan-Meier life table analysis identified survival rates of 94% (SD ± 5.9), 20.1% (SD ± 9.0) and 6.7% (SD ± 4.6) at 1, 3 and 5 years, respectively. Two patients are alive: one of them had adrenal metastases from renal cancer and is disease-free after a 12-month follow-up; the other, who had a metastasis from breast cancer, is alive with disease at 48 months of follow-up. The other 14 patients died of metastatic spread to other or- gans, and one of them also had a local recurrence after 8 months, which was treated by with local en-bloc excision of peri-renal fat and splenectomy via a laparotomy.
Discussion
The role of minimally-invasive surgery for adrenal malig- nancies remains controversial. The number of patients suc- cessfully undergoing laparoscopic adrenalectomy reported by most authors is small, and many studies have failed to stratify patients according to whether they had primary adrenal cancer or metastatic disease.6,8,12,14-17 In our opinion, these two conditions must be assessed separately, considering 2 different patient groups, i.e. cases of adrenocortical carci- noma and cases with adrenal metastases.
Adrenocortical carcinoma is a rare tumor, occurring in 1-2 cases per million population a year, but it is highly malignant and only radical surgical resection has a chance of being curative.
Primary adrenal cancer generally presents as a large mass (its mean diameter was 9.6 cm in our series) and it may secrete cortisol, aldosterone and androgens, alone or in combination. We found only one non-secreting tumor. Preoperative radio- logical investigations are able to detect local invasion to adjacent structures or lymph node and distant metastases, enabling the appropriate, i.e. open or laparoscopic, surgical approach to be planned. In cases with distant metastases, resection of the adrenal cancer does not extend the patient’s survival but it can reduce the symptoms of endocrine excess.
In a recent study, Carnaille said that laparoscopic adrena- lectomy is not indicated for adrenocortical carcinoma and open surgery is to be recommended.18 Scheteingart et al. had already come to the same conclusion, as reported at an in- ternational consensus conference. 19
Saunders et al. were of like mind regarding the role of laparoscopy, that they said should be used for exploratory purposes, prompting a decision to convert to open surgery if it reveals any signs of malignant disease. The authors suggested that any use of laparoscopy should be limited in any case to tumors less than 6 cm in size.20
Adrenocortical carcinomas are usually large masses by the time they are detected because they often cause no symp- toms, or only the non-specific symptoms of subclinical Cushing’s syndrome, and also because the preoperative diagnosis of adrenal carcinoma is very difficult.2º Kebebew
et al. reported, for instance, that only 1 of their 6 patients with primary adrenal cancer was suspected of having a malignancy preoperatively.15
The risk of tumor spillage or inadequate margin resection and the intraoperative aspects of malignancies explain the high rate of conversion to open surgery in our series: 83.3%, partly due to the larger diameter of the adrenocortical carcinomas concerned, i.e. 9.6 cm as opposed to 3.2 cm of the adrenal me- tastases. When the tumor is large, it becomes difficult to create sufficient space to work in without touching the tumor.16
Brix et al. reported on a large series of adrenal carcinoma patients and judged that laparoscopic access did not differ from open surgery as regards oncological outcome, but only 35 patients in their series were treated laparoscopically, and 12 of them (34.2%) were converted to open surgery.17 In another study, only 5/175 patients were treated laparoscopically.21
On the contrary, Porpiglia et al. also reported a similar outcome in a fair number of patients, in stage I and II, who underwent open or laparoscopic surgical resection, with a low percentage of conversion.9
Other major limitations on the use of a laparoscopic access are the related risks of loco-regional or port-site recurrences and diffuse peritoneal carcinomatosis, as documented by several studies.10-12,22,23 The high risk of diffuse carcinoma- tosis also emerges clearly from the study by Lombardi et al., in which almost half of the patients who underwent laparo- scopic adrenalectomy developed peritoneal recurrences.6
In our series, there was one case of peritoneal dissem- ination even though the initially laparoscopic access had been promptly converted to open surgery.
On the whole, based on our experience of adrenal surgery performed by the same surgeon - which includes more than 300 laparoscopic adrenalectomies for benign disease over a 20-year period,4,5 - we, like Miller et al.,23 conclude that laparoscopic resection is inappropriate for patients with known or suspected adrenocortical carcinoma, especially given the high percentage (more than 50%) of positive margins seen in their laparoscopically-treated group.
In a recent review, Gaujoux et al. claimed that lymphade- nectomy as an important prognostic factor in patients with adrenocortical carcinoma, and they too concluded that lapa- roscopy should be avoided for this tumor.24
Metastasis to the adrenal gland should be suspected in patients with adrenal incidentaloma and a history of cancers most frequently metastasizing to the lung, breast, kidney, or colon.
Many reports in the literature have documented successful laparoscopic adrenalectomies in cases with solitary metasta- ses, achieving a very low incidence of local recurrences or peritoneal dissemination.3,7,12,25
In our opinion, the main aspect to consider for the success of laparoscopy is a small size of the adrenal tumor (usually found in patients being closely followed up due to a prior cancer). In our series, the mean diameter of such metastases was 3.2 cm and we performed laparoscopic adrenalectomy in 93.3% of these cases. We recommend excision of any adrenal metastases without touching the tumor or the gland, the surgeon should start the procedure from the perirenal fat tissue, to avoid the risk of tumor spillage or incomplete resection. It takes a skilled surgeon to resect metastases and
we suggest to start the adrenalectomy by searching the renal and phrenic vein on the left, the renal vein and inferior vena cava on the right, without touching the adrenal area. After closing the adrenal vein, we perform en-bloc adrenalectomy, including the surrounding adipose tissue.
As we and other authors have previously reported, intra- operative endoscopic ultrasound can be of the utmost importance, also providing important information on the size of the tumor and its anatomical relationship with the healthy tissue.7,26-28
The choice of type approach (open or laparoscopy) was secondary to the size and imaging features of the lesion. Therefore there was not shift from type of approach to another.
About the learning curve of the surgeons, the last period of our laparoscopic experience included a few cases of conver- sion to open after initially attempting laparoscopy in patients who, in the first period would probably have been submitted to open surgery from the outset.
Mean operating time was progressively shorter, with a highly significant difference (p < 0.0001).
Our recently - published paper4 showed that the surgeon’s experience had a high impact only on the operating time, not on morbidity or rate of conversion.
In conclusion, many studies have documented that resecting adrenal metastases contributes to a more favorable prognosis than when these tumors are not resected25,29-31 and, in agreement with Zografos et al., our study shows that the laparoscopic approach can be justified and is feasible only in case of adrenal metastases.10 Judging from our experience, laparoscopic adrenalectomy for solitary metastases offers the same advantages as those amply reported for benign adrenal disease, with a minimal morbidity, no mortality, and the same oncological results as open surgery.
Disclosures
Dr. Antonio Toniato has no conflict of interest or financial ties to disclose.
REFERENCES
1. Murphy MM, Witkowski ER, Ng SC, McDade TP, Hill JS, Larkin AC, et al. Trends in adrenalectomy: a recent national review. Surg Endosc 2010, Oct;24(10):2518-26.
2. Park HS, Roman SA, Sosa JA. Outcomes from 3144 adrenalectomies in the United States: which matters more, surgeon volume or specialty? Arch Surg 2009;144:1060-7.
3. Ramacciato G, Mercantini P, La Torre M, Di Benedetto F, Ercolani G, Ravaioli M, et al. Is laparoscopic adrenalectomy safe and effective for adrenal masses larger than 7 cm? Surg Endosc 2008;22:516-21.
4. Toniato A, Boschin I, Bernante P, Foletto M, Guolo AM, Pelizzo MR, et al. Factors influencing the rising rates of adrenal surgery: analysis of a 25-year experience. Surg Endosc 2009, Mar;23(3):503-7.
5. Toniato A, Merante-Boschin I, Opocher G, Pelizzo MR, Schiavi F, Ballotta E. Surgical versus conservative management for subclinical Cushing syndrome in adrenal
incidentalomas: a prospective randomized study. Ann Surg 2009, Mar;249(3):388-91.
6. Lombardi CP, Raffaelli M, De Crea C, Bellantone R. Role of laparoscopy in the management of adrenal malignancies. J Surg Oncol 2006, Aug 1;94(2):128-31.
7. Henry JF, Sebag F, Iacobone M, Mirallie E. Results of laparoscopic adrenalectomy for large and potentially malignant tumors. World J Surg 2002;26:1043-7.
8. McCauley LR, Nguyen MM. Laparoscopic radical adrenalectomy for cancer: long-term outcomes. Curr Opin Urol 2008;18:134-8.
9. Porpiglia F, Fiori C, Daffara F. Retrospective evaluation of the outcome of open versus laparoscopic adrenalectomy for stage I and II adrenocortical cancer. Eur Urol 2010;57:873-8. 2010.
10. Zografos GN, Vasiliadis G, Farfaras AN, Aggeli C, Digalakis M. Laparoscopic surgery for malignant adrenal tumors. JSLS 2009, Apr-Jun;13(2):196-202.
11. Suzuki K, Ushiyama T, Mugiya S, Kageyama S, Saisu K, Fujita K. Hazards of laparoscopic adrenalectomy in patients with adrenal malignancy. J Urol 1997;158(6):2227.
12. Moinzadeh A, Gill IS. Laparoscopic radical adrenalectomy for malignancy in 31 patients. J Urol 2005;173(2):519-25.
13. Fassnacht M, Johanssen S, Quinkler M, Bucsky P, Willenberg HS, Beuschlein F, et al. Limited prognostic value of the 2004 International Union against Cancer staging classification for adrenocortical carcinoma: proposal for a revised TNM classification. Cancer 2009;115(2):243-50.
14. Sturgeon C, Kebevev E. Laparoscopic adrenalectomy for malignancy. Surg Clin North Am Jun 2004;84(3):755-74.
15. Kebebew E, Siperstein AE, Clark OH, Duh QY. Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms. Arch Surg Aug; 2002;137(8):948-51.
16. Suzuki H. Laparoscopic adrenalectomy for adrenal carcinoma and metastases. Curr Opin Urol Mar; 2006;16(2):47-53.
17. Brix D, Allolio B, Fenske W, Agha A, Dralle H, Jurowich C, et al. Laparoscopic versus open adrenalectomy for adrenocortical carcinoma: surgical and oncologic outcome in 152 patients. Eur Urol Oct; 2010;58(4):609-15.
18. Carnaille B. Adrenocortical carcinoma: which surgical approach? Langenbecks Arch Surg 2012, Feb;397(2):195-9.
19. Schteingart DE, Doherty GM, Gauger PG, Giordano TJ, Hammer GD, Korobin M, et al. Management of patients with adrenal cancer: recommendations of an international consensus conference. Endocr Relat Cancer 2005;12(3):667-80.
20. Saunders BD, Doherty GM. Laparoscopic adrenalectomy for malignant disease. Lancet Oncol 2004, Dec;5(12):718-26.
21. Hermsen IG, Kerkhofs TM, Butter Gd, Kievit J, van Eijck CH, Nieveen van Dijkum EJ, et al. Surgery in adrenocortical carcinoma: importance of national cooperation and centralized surgery. Surgery 2012, Jul;152(1):50-6.
22. Leboulleux S, Deandreis D, Al Ghuzlan A, Aupérin A, Goéré D, Dromain C, et al. Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis? Eur J Endocrinol 2010, Jun;162(6):1147-53.
23. Miller BS, Ammori JB, Gauger PG, Broome JT, Hammer GD, Doherty GM. Laparoscopic resection is inappropriate in patients with known or suspected adrenocortical carcinoma. World J Surg 2010;34:1380-5.
24. Gaujoux S, Brennan MF. Recommendation for standardized surgical management of primary adrenocortical carcinoma. Surgery 2012, Jul;152(1):123-32.
25. Marangos IP, Kazaryan AM, Rosseland AR, Røsok BI, Carlsen HS, Kromann-Andersen B, et al. Should we use laparoscopic adrenalectomy for metastases? Scandinavian multicenter study. J Surg Oncol 2009, Jul 1;100(1):43-7.
26. Toniato A, Meduri F, Foletto M, Avogaro A, Pelizzo M. Laparoscopic treatment of benign insulinomas localized in
the body and tail of the pancreas: a single-center experience. World J Surg 2006, Oct;30(10):1916-9 [discussion 1920-1].
27. Lo CY, Lo CM, Fan ST. Role of laparoscopic ultrasonography in intraoperative localization of pancreatic insulinoma. Surg Endosc 2000;14:1131-5.
28. Lo CY, Chan WF, Lo CM, Fan ST, Tam PK. Surgical treatment of pancreatic insulinomas in the era of laparoscopy. Surg Endosc 2004;18:297-302.
29. Luketich JD, Burt ME. Does resection of adrenal metastases from non-small cell lung cancer improve survival? Ann Thorac Surg 1996;62:1614-6.
30. Lo CY, van Heerden JA, Soreide JA, Grant CS, Thompson GB, Lloyd RV, et al. Adrenalectomy for metastatic disease to the adrenal glands. Br J Surg 1996;83:528-31.
31. Sarela AI, Murphy I, Coit DG, Conlon KC. Metastasis to the adrenal gland: the emerging role of laparoscopic surgery. Ann Surg Oncol 2003;10:1191-6.