- Email: [email protected]
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY IN 31 PATIENTS
0022-5347/05/1732-0519/0 THE JOURNAL OF UROLOGY® Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 173, 519 –525, February 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000149038.89467.30
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY IN 31 PATIENTS ALIREZA MOINZADEH
AND
INDERBIR S. GILL*
From the Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
Purpose: Laparoscopic adrenalectomy for malignancy is controversial. We analyzed our experience with laparoscopic radical adrenalectomy for cancer with an emphasis on predictors of surgical outcome and oncological followup data. Materials and Methods: Since July 1997, 31 patients have undergone a total of 33 laparoscopic adrenalectomies for malignancy. Mean adrenal tumor size was 5 cm (range 1.8 to 9). The laparoscopic approach was transperitoneal in 17 cases, retroperitoneal in 15 and transthoracic in 1. Data were obtained from patient charts, radiographic reports and direct telephone calls to patient families. Results: Associated organ resection (radical nephrectomy) was performed in 3 patients. One case was electively converted to open surgery. There was no operative mortality. The pathological diagnoses were metastatic cancer in 26 cases and primary adrenal malignancy in 7. Current median followup, available on 30 patients, was 26 months (range 1 to 69). Overall 15 patients (48%) died and 16 (52%) were alive, of whom 13 (42%) showed no evidence of disease. Cancer specific survival at a median followup of 42 months was 53% and 5-year actuarial survival was 40%. Local recurrence was noted in 7 patients (23%). There were no port site metastases. Survival was similar in patients with tumors less than 5 cm vs 5 cm or greater. Survival was not associated with patient age, tumor size, operative time or surgical approach. Survival was compromised in patients with local recurrence (p ⫽ 0.016). Conclusions: Laparoscopic radical adrenalectomy can be performed with acceptable outcomes in the carefully selected patient with a small, organ confined, solitary adrenal metastasis or primary adrenal carcinoma. To our knowledge the largest series in the literature to date is presented. KEY WORDS: adrenal glands, laparoscopy, adrenalectomy, neoplasm metastasis, adrenal gland neoplasms
Laparoscopic adrenalectomy has become the gold standard approach for benign surgical adrenal disorders such as aldosteronoma, Cushing’s disease and pheochromocytoma. However, laparoscopic adrenalectomy for solitary metastasis or primary adrenal cancer remains a matter of considerable controversy. Concern rightfully exists over the possibility of carcinomatosis or port site metastasis, as noted in the initial published case reports.1–7 However, recent small series have described laparoscopic adrenalectomy for malignancy with acceptable oncological outcomes.8 –14 Given the controversial nature of this topic, we reviewed our single institution, single surgeon experience with laparoscopic adrenalectomy for malignancy. Perioperative outcomes and oncological followup with a focus on predictors of survival are presented and the relevant literature is reviewed. MATERIALS AND METHODS
Since 1997, we have performed more than 250 laparoscopic adrenalectomies at our institution. Of them 31 patients (33 adrenalectomies) with pathologically confirmed adrenal malignancy were identified retrospectively. The cohort included patients with preoperative suspicion of a solitary metastasis to the adrenal gland and those who were incidentally found to have primary adrenal malignancy. Four additional patients with preoperatively presumed metastasis to the adre-
nal gland malignancy who were found to have benign adenoma on the final pathological report were excluded. Patients who underwent concomitant adrenalectomy during radical nephrectomy for renal cell carcinoma (RCC) were excluded. Selection criteria for the laparoscopic approach were an adrenal mass of 10 cm or less without evidence of peri-adrenal infiltration, caval thrombus or bulky locoregional lymphadenopathy on preoperative computerized tomography (CT). All patients underwent complete preoperative staging, including a detailed history and physical exam, radiographic imaging and endocrine assessment as indicated. Abdominal imaging was primarily 3-dimensional CT with 3 mm adrenal cuts and rarely magnetic resonance imaging or metaiodobenzylguanidine scanning. Followup comprised physical examination, chest x-ray and abdominal/pelvic CT 6 months postoperatively and yearly thereafter at the discretion of the local physician. Patient charts were retrospectively reviewed to establish demographic data. Cancer recurrence and patient survival were determined by a review of radiographic reports (abdominal CT scan/chest x-ray) and chart review. When direct survival data were not current, telephone calls were made to patients or family members by one of us (AM). The diseasefree interval as a predictor of survival was assessed. In patients with a solitary adrenal metastasis the disease-free interval was defined as the time elapsed between treatment of the initial primary cancer and diagnosis of the adrenal mass. Adrenal metastasis discovered within 6 months of treatment of the nonadrenal primary tumor was defined as synchronous, while metastasis discovered more than 6
Submitted for publication June 2, 2004. * Correspondence and requests for reprints: Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic Foundation, 9500 Euclid Ave. A-100, Cleveland, Ohio 44195 (FAX: 216-445-7031; e-mail: [email protected]). 519
520
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY
months later was defined as metachronous. Survival analysis was done using the Kaplan-Meier method with log rank testing for categorical predictors. The Cox regression model was used to assess the association between continuous predictor variables and survival. RESULTS
A total of 33 adrenalectomies were performed in 31 patients. There were 19 males and 12 females with a mean age of 59.8 years (range 38 to 79). Mean tumor size was 5 cm (range 1.8 to 9). No patient had evidence of systemic metastatic disease except 1 patient with diffusely metastatic melanoma who underwent palliative laparoscopic adrenalectomy to minimize the risk of sudden retroperitoneal bleeding, which had occurred in the contralateral adrenal gland. Five patients (16%) underwent preoperative needle biopsy at the referring institution, of which 2 were diagnostic for metastatic disease and 1 was suggestive of the final diagnosis of sarcoma (table 1). The laparoscopic approach used at the discretion of the surgeon (ISG) was transperitoneal in 17 cases, retroperitoneal in 15 and transthoracic in 1. A review of individual operative reports indicated that 4 patients had evidence of local invasion, including to the inferior vena cava and kidney in 1 patient (the only one in this series who was electively converted to open surgery), liver in 1, desmoplastic changes secondary to local infiltration necessitating ipsilateral nephrectomy in 1 and lymph node positive disease in 1 with pheochromocytoma who underwent concomitant radical nephrectomy. One patient with a 5 cm left adrenal mass was intraoperatively detected to have adrenal vein thrombus entering the main left renal vein. Pure laparoscopic techniques were used to occlude the renal artery and vein with a Satinsky clamp, incise the left renal vein, perform en bloc extraction of the venous thrombus along with the adrenal tumor, suture repair the renal vein and revascularize the kidney.15 Pathology reports indicated a diagnosis of adrenal metastasis in 26 patients, primary adrenal cell carcinoma in 6 and malignant pheochromocytoma in 1 (table 1). Surgical margins of the adrenalectomy specimen were negative for cancer in 19 cases (56%), indeterminate in 2 (6%) and positive in 1 (3%). The pathology report made no mention of margin status in 11 patients (33%). Two patients had previously received chemotherapy for the primary malignancy (sarcoma and
TABLE 1. Demographic, operative and pathological data No. pts No. procedures No. gender: Male Female No. side: Lt Rt Bilat No. approach: Transperitoneal Retroperitoneal Transthoracic Mean cm mass size on CT (range) Mean gm specimen wt (range) Mean estimated blood loss (ml) Mean operative time (mins) Hospital stay (days) No. pathological diagnosis: Renal cell Ca metastasis Adrenal cell Ca Colonic metastasis Lung metastasis Metastatic sarcoma Malignant pheochromocytoma Metastatic melanoma NonHodgkin’s lymphoma
31 33
TABLE 2. Overall patient outcome Pt Outcome
No. Pts (%)
No disease evidence Alive with disease Dead of disease Dead of other causes Lost to followup
13 (42) 3 (10) 13 (42) 1 (3) 1 (3)
No. Local Recurrence 1 6
Median Followup (mos) 37 46 17 3 2
lung), while 4 received chemotherapy or immunotherapy after laparoscopic adrenalectomy. There was no operative mortality. Complications occurred in 4 patients (13%), including inferior epigastric injury repaired laparoscopically in 1, atelectasis and fever on day 2 in 1 and port site hernia in 2. Two patients required blood transfusion. In each case adhesions and/or capsular vessels resulted in intraoperative blood loss greater than 500 ml but there was no technical complication. Followup data were available on 30 patients (97%) with an overall median duration of 26 months (table 2). The 5-year Kaplan-Meier survival estimate in the cohort of 30 patients was 40% (see figure). At last followup 16 patients (53%) were alive at a median of 42 months (range 1 to 63). The remaining 14 patients (47%) died at a median of 13 months (range 1 to 29) after the laparoscopic procedure. Of these 14 patients 11 (35%) died of metastatic disease and 3 died of causes unrelated to cancer. Local recurrence was noted in 7 patients (23%), including 3 with metastatic RCC, 2 with metastatic colon cancer and 2 with primary adrenal cortical carcinoma (table 3). In these 7 patients mean adrenal tumor size was 5.5 cm (range 1.8 to 8.6) and the laparoscopic approach was transperitoneal in 4 and retroperitoneal in 3. Mean blood loss was 485 cc (range 100 to 1,200) and mean operative time was 237 minutes (range 175 to 370). Associated organ resection was not performed in any patient. In the 7 patients with local recurrence the final pathology report indicated that the adrenalectomy surgical margin was negative for cancer in 4, indeterminate in 1, positive in 1 and not documented in 1. Six of the 7 patients (86%) with local recurrence died with a median survival of 17 months (range 9 to 52). One patient with metastatic RCC, including bilateral metastatic adrenal masses, had evidence of peritoneal carcinomatosis 7 months after laparoscopic adrenalectomy. Patients with local recurrence had significantly decreased 3-year survival compared to those without local recurrence (16.7% vs 66%, p ⫽ 0.016). Preoperatively cancer of the adrenal gland was suspected in 28 of 31 patients (90%) based on CT findings and clinical history. In the 3 patients who were preoperatively not sus-
19 12 15 14 2 17 15 1 5 (1.8–10) 116 (10–678) 258 181 2.1 13 6 5 4 2 1 1 1
Overall 5-year actuarial plot of survival in all 30 patients in series.
Lt Lt Rt Lt Lt Lt Lt
Rt
Rt
Lt Rt Lt Lt Rt
Side
Transperitoneal Retroperitoneal Transperitoneal Retroperitoneal Retroperitoneal Transperitoneal Transperitoneal Transperitoneal in 4 cases, retroperitoneal in 3
Retroperitoneal Transperitoneal in 3 cases, retroperitoneal in 4
Transperitoneal Transperitoneal Retroperitoneal Retroperitoneal Transperitoneal, converted to open Retroperitoneal
Laparoscopic Approach
175 180 270 195 Not available† 230 370 237
45 202
150
315 290 120 255 240
Operative Time (mins)
100 500 1,200 600 100 600 300 486
25 160
100
200 100 100 100 500
Estimated Blood Loss (cc)
Yes Yes Yes Yes 5
Yes
Yes 7
Yes
Yes Yes Yes Yes Yes
Incomplete
2
Yes Yes
Local recurrence
No local recurrence
Complete
Surgical Resection*
RCC Colon ACC RCC Colon RCC ACC —
ACC —
Lung
RCC RCC Melanoma Colon ACC
Pathological Findings
Neg Not available† Fractured specimen Neg Not available† Neg Neg Neg in 4 cases, not available in 2
Neg Neg in 5 cases, not available in 2
Neg
Not available† Not available† Neg Neg Neg
Surgical Margins
TABLE 3. Patients with resulting mortality or local recurrence
* Subjective surgeon opinion, as documented in operative note. † Not reported on final pathology report with all pathology reports available for review and no data lost.
1.8 7 8.6 8.2 5.1 3.0 5.0 5.5
6—57—M
8—66—M 9—79—F 10—55—M 11—57—M 12—70—M 13—51—M 14—43—F Means or totals—60.1
7
1—60—F 2—68—M 3—40—M 4—72—M 5—70—M
3.6 4.5
2.4 4.2 3 2.5 9
Pt.—Age—Sex No.
7—57—F Means or totals—60.6
CT Tumor Size (cm)
Yes Yes Yes Yes Yes Yes Yes Yes in 7 cases
No No in 7 cases
No
No No No No No
Local Recurrence
52 13 25 9 13 21 Alive with disease 22.1
17 17.7
4
48 26 2 26 1
Time to Death (mos)
Lung, liver Rt adrenal metastases Lung Peritoneal carcinomatosis Lung Brain, spine Retroperitoneum —
Lung, liver metastases at laparoscopic adrenalectomy Lung, liver —
Brain Lung, brain Pelvic bone, brain Not available Not available
Metastatic Sites ⫹ Comments
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY
521
522
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY TABLE 4. Patients with adrenal tumors less than 5 vs 5 cm or greater Tumor Size (cm) Less Than 5
5 or Greater
p Value
No. pts 17 16 — No. men (%) 12 (71) 8 (50) 0.23 (chi-square test) No. rt side (%) 6 (35) 10 (63) 0.12 (chi-square test) Mean tumor size (cm) 3.1 6.6 ⬍0.001 (t test) No. transperitoneal approach (%) 10 (65) 6 (38) 0.87 (chi-square test) Median estimated blood loss (cc) 175 300 0.15 (t test) Mean operative time (mins) 192 207 0.62 (t test) No. operative resection: 0.07 (exact unconditional test) Complete 17 13 Incomplete 0 3 Median hospital stay (days) 1.0 2.0 0.15 (t test) No. pathological findings (%): 0.17 (exact unconditional test) Metastasis 15 (88) 11 (69) Primary 2 (12) 5 (31) No. surgical pathological margins: 0.72 (chi-square test) Pos 0 1 Neg 9 10 Indeterminate 1 1 Not documented on final pathology report 7 4 No. local recurrence (%) 2 (12) 5 (31) 0.17 (exact unconditional test) Median specimen wt (gm) 28 78 0.07 (Mann-Whitney test) No. alive at last followup/total no. (%) 9/16 (56) 8/15 (53) 0.87 (chi-square test) Mean followup (mos) 33.4 21 0.11 (t test) The 2 groups were compared on binary variables using the chi-square or exact unconditional test, on normally distributed continuous variables using the t test and on nonnormally distributed continuous variables using the Mann-Whitney test.
pected of having malignant adrenal disease the final pathology report identified adrenocortical carcinoma (ACC) in 2 and nonHodgkin’s lymphoma in 1. Six of the 26 patients with adrenal metastasis had synchronous and 19 had metachronous disease with data not available on 1. There was no difference in survival between the synchronous and metachronous groups (log rank test p ⫽ 0.96). Survival was not associated with gender (p ⫽ 0.11), age (p ⫽ 0.36), tumor size (p ⫽ 0.14), tumor side (p ⫽ 0.54), estimated blood loss (p ⫽ 0.41), specimen weight (p ⫽ 0.71), operative time (p ⫽ 0.68) or transperitoneal vs retroperitoneal laparoscopic surgical approach (p ⫽ 0.11). There was no survival difference in patients with solitary metastasis to the adrenal gland compared to those with primary adrenal malignancy (log rank test p ⫽ 0.99). Five-year survival was similar in patients with an adrenal tumor of less than 5 vs 5 cm or greater (36% vs 46%, p ⫽ 0.43, table 4). Since RCC comprised 13 of the 26 metastatic cases (50%), we performed a comparison of survival between the RCC, ACC, colon cancer and lung cancer groups, and found no survival difference (log rank test p ⫽ 0.28). DISCUSSION
The rationale for surgical excision of solitary adrenal metastases has previously been addressed. In general the prognosis of patients with metastatic disease is poor with few survivors at 5 years. In regard to nonsmall cell lung cancer Luketich and Burt reported on 14 patients with isolated adrenal metastasis from lung cancer.16 Median survival in the open surgical resection plus chemotherapy group of 6 patients was greater than in the chemotherapy alone group of 6 (31 vs 8.5 months, p ⫽ 0.03). In our series 4 patients with adrenal metastasis from lung cancer had an overall median followup of 25 months, of whom 2 are currently alive without evidence of disease. In regard to RCC Lau et al reported on 11 patients undergoing contralateral open surgical resection for adrenalectomy for metastasis and reviewed the literature.17 In 20 publications 27 of 56 patients (48%) were alive at last followup (range 0.3 to 14.3 years). Heniford et al identified 38 cases of synchronous or metachronous contralateral adrenal metastasis from RCC in the literature.8 A total of 35 patients underwent laparoscopic or open resection of adrenal metastasis with 62% having no evidence of disease at an average
followup of 26 months. In our series 6 of the 13 patients (46%) with metastatic RCC were alive at a median followup of 39 months. In regard to primary ACC overall 5-year survival after open surgery has been reported to be 25%. Five-year survival increases to almost 50% if complete resection is achieved at the time of curative surgery. In the series of Henry et al 5 of 6 patients were disease-free at a median followup of 27.5 months.10 In a report of 179 patients undergoing open adrenalectomy for ACC Bellantone et al documented local recurrence in 52 (37%).18 Our 33% incidence of local recurrence for ACC compares favorably with this open surgery experience. Three of the 6 patients (50%) with ACC in our series were alive at a median followup of 21 months, including 2 without evidence of disease and 1 undergoing chemotherapy. In our series overall 5-year actuarial survival was 40% at a median followup of 26 months. These results compare favorably with those in a prior open series from Memorial SloanKettering Cancer Center (MSKCC).19 In the MSKCC report 37 patients undergoing open adrenalectomy for nonprimary adrenal malignancy were found to have a 5-year actuarial survival of 24% with a median survival of 21 months. The MSKCC series also documented improved survival when the pre-adrenalectomy disease-free interval was greater than 6 months,13, 19 a finding that was not confirmed by our data. A possible explanation is the different distribution of the nonadrenal primary malignancy in these series. In the 2 MSKCC reports a lung primary tumor was present in 46% and 56% of patients, respectively. In our cohort lung cancer comprised only 15% of cases, while RCC comprised 50%. If one believes that the disease-free interval is a surrogate for the intrinsic biological aggressiveness of the primary tumor and recognizes that RCC may lead to metastasis years after resection of the renal primary lesion, it is plausible to accept the differences between these 2 series in regard to the diseasefree interval. An objective of our study was to identify potential predictors of survival in this patient population. On univariate analysis age, gender, specimen weight, estimated blood loss, operative time and tumor size/side were not found to have prognostic significance in regard to patient survival. Similarly patients with an adrenal tumor of less than 5 cm compared to those with a tumor of 5 cm or greater had compa-
Final reoperation
ACC
Hofle et al3
Local, carcinomatosis
4
Uncomplicated
Not available
43 F Lt 3 Cushing’s syndrome
Hamoir et al4
Deckers et al5
Transperitoneal
74 M Rt 2.7 Conn’s syndrome
Carcinomatosis
6
Foxius et al6
Benign
Local, carcinomatosis
6
Uncomplicated
Transperitoneal
74 M Rt 2.7 Conn’s syndrome
Chen et al7
Nonsmall cell lung Ca
Carcinomatosis including port site recurrence
Intraop mass had increased to 8 ⫻ 6 cm, specimen removed intact in entrapment sack 5
Transperitoneal
55 F Lt 2.5 Nonsmall cell lung Ca
Same features as initial tumor Identical to initial tumor, Nonsmall cell lung Ca with increased cellularity ⫹ deemed ACC based on necrosis consistent with clinical metastasis ACC
Benign
Carcinomatosis
10
“Difficult ⫹ bloody,” con- Partial adrenalectomy version to open procedure
25 F Rt 12 Secondary amenorrhea ⫹ virilization Not available
Poorly differentiated lung “Undetermined” malignant Benign Ca potential Poorly differentiated lung Could not confirm ACC due ACC Ca to fragmented tumor
“Multiple metastases”
Local, carcinomatosis
Pathological findings: Initial specimen Benign adenoma
8
14
Conversion to open surgery, en bloc removal of part of kidney
Uncomplicated
Time to recurrence (mos) Recurrence site
Not available
Not available
Laparoscopic approach Surgery comment
62 M Lt 5.5 Lung adenoca
50 F Lt 5 Cushing’s syndrome
Pt age Sex Side Tumor size (cm) History
Suzuki et al2
TABLE 5. Literature review of single case reports questioning laparoscopic adrenalectomy safety in setting of malignancy
Ushiyama et al1
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY
523
524
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY TABLE 6. Literature review of series of laparoscopic adrenalectomy for cancer References
No. Pts
Heniford et al8 Valeri et al9 Henry et al10 Kebebew et al11
11 6 6 18
Lombardi et al12
9
Sarela et
al13
11
Followup (mos)
Comments
Mean 8.3 Mean 8.6 Median 27.5 Mean 39.6 Mean 17 Median 21
6 Mean 19.5 in 2 pts who died ⫹ 7 in 4 survivors Feliciotti et al14 Present series 31 Median 26 Only series with 5 or more patients are included.
rable overall outcomes and survival at a followup of 33.4 and 21 months, respectively (table 4). In the last few years 7 initial case reports questioned the adequacy of the laparoscopic approach for malignant adrenal tumors (table 5).1– 6 Briefly, these 7 reports of a single patient each described locally recurrent malignancy shortly after laparoscopic adrenalectomy, that is within 4 to 14 months. Two of these 7 patients had a lung primary lesion metastatic to the adrenal gland. The remaining 5 cases, initially thought to be benign, were only later diagnosed by final histopathological findings as adrenocortical carcinoma. Laparoscopy was hypothesized to have potentially had a role in tumor dissemination in each case. However, no clear evidence as such was provided with minimal discussion about the central issues of the innate aggressive nature of the tumor or details about the adequacy of the laparoscopic technique used. More recently a few series of a limited number of patients undergoing laparoscopic adrenalectomy for malignancy have been reported (table 6).8 –14 Although the number of patients in each individual series was small and followup was short, certain inferences can be drawn. In the 100 aggregate patients in these 8 series, including ours, only 1 had carcinomatosis and no port site recurrences were reported. This stands in stark contrast to the 100% incidence of carcinomatosis and/or port site recurrence documented in single case reports (table 5). This wide discrepancy in outcomes between individual case reports and patient series raises suspicion about the technical adequacy of laparoscopic techniques among institutions (tables 5 and 6). Additionally, the inherent nature of malignancy may vary similarly. Port site metastasis is a rare occurrence in urological laparoscopy. In a recent review of more than 2,000 cases of laparoscopic oncological surgery Tsivian and Sidi reported 11 (0.6%) of port site metastasis.20 Based on this review they concluded that factors contributing to port site metastasis include biological tumor aggressiveness, surgical violation of the tumor boundary, not using a specimen extraction sack and ascites. With proper patient selection and adherence to meticulous, skilled laparoscopic technique the majority of port site metastases can be avoided. Carcinomatosis has been hypothesized possibly to occur from the dispersion of malignant cells by carbon dioxide gas, tumor spillage due to inadvertent violation of the involved organ, extraction site contamination by tumor cells and the questionable immunosuppressive effect of pneumoperitoneum. In clinical studies Ikramuddin et al used a saline trap intraoperatively to capture effluent CO2 in 35 patients undergoing elective laparoscopic procedures.21 Although 15 patients had malignancies, only 2 were found to have malignant cells in the effluent. These 2 patients had preexisting carcinomatosis. As such, Ikramuddin et al concluded that it was unlikely that cell aerosolization was a significant contributor to port site metastasis. Currently our main adrenal specific contraindication to lapa-
10/11 Pts (91%) disease-free 3/6 Pts (50%) disease-free All pts with ACC, 5/6 (93%) disease-free 9/13 Pts (69%) with metastatic disease to adrenal gland ⫹ 2/5 (40%) with primary ACC disease-free 9/11 Pts (82%) disease-free, 1 dead of unrelated cause About 60% survival, 11 laparoscopic vs 20 open radical adrenalectomies showed no difference in overall survival 4/6 Pts (67%) disease-free 13/31 Pts (42%) disease-free
roscopic adrenalectomy is an irregular adrenal mass with periadrenal infiltration, as noted on 3-dimensional CT with 3 mm adrenal cuts, which is our preferred imaging modality. For surgeons with advanced laparoscopic experience size per se is a less important issue, although we generally limit laparoscopic adrenalectomy to tumors in the 10 cm range. Intraoperative concern regarding the adequacy of wide excision should prompt the consideration of open conversion. CONCLUSIONS
At intermediate term followup our local recurrence and cancer specific survival rates following laparoscopic adrenalectomy for cancer appear to be in concordance with those of published open series. Along with other recent publications this report suggests that in the carefully selected patient with a small, organ confined adrenal malignancy laparoscopic radical adrenalectomy is safe and efficacious. Since local recurrence is associated with a poor prognosis, complete en bloc excision is important. If concerns exist regarding the adequacy of wide margin dissection, the threshold for open conversion should be low. Meng Xu provided statistical analyses and support. REFERENCES
1. Ushiyama, T., Suzuki, K., Kageyama, S., Fujita, K., Oki, Y. and Yoshimi, T.: A case of Cushing’s syndrome due to adrenocortical carcinoma with recurrence 19 months after laparoscopic adrenalectomy. J Urol, 157: 2239, 1997 2. Suzuki, K., Ushiyama, T., Mugiya, S., Kageyama, S., Saisu, K. and Fujita, K.: Hazards of laparoscopic adrenalectomy in patients with adrenal malignancy. J Urol, 158: 2227, 1997 3. Hofle, G., Gasser, R. W., Lhotta, K., Janetschek, G., Kreczy, A. and Finkenstedt, G.: Adrenocortical carcinoma evolving after diagnosis of preclinical Cushing’s syndrome in an adrenal incidentaloma. A case report. Hormone Res, 50: 237, 1998 4. Hamoir, E., Meurisse, M. and Defechereux, T.: Is laparoscopic resection of a malignant corticoadrenaloma feasible? Case report of early, diffuse and massive peritoneal recurrence after attempted laparoscopic resection. Ann Chir, 52: 364, 1998 5. Deckers, S., Derdelinckx, L., Col, V., Hamels, J. and Maiter, D.: Peritoneal carcinomatosis following laparoscopic resection of an adrenocortical tumor causing primary hyperaldosteronism. Horm Res, 52: 97, 1999 6. Foxius, A., Ramboux, A., Lefebvre, Y., Broze, B., Hamels, J. and Squifflet, J.: Hazards of laparoscopic adrenalectomy for Conn’s adenoma. When enthusiasm turns to tragedy. Surg Endosc, 13: 715, 1999 7. Chen, B., Zhou, M., Cappelli, M. C. and Wolf, J. S., Jr.: Port site, retroperitoneal and intra-abdominal recurrence after laparoscopic adrenalectomy for apparently isolated metastasis. J Urol, 168: 2528, 2002 8. Heniford, B. T., Arca, M. J., Walsh, R. M. and Gill, I. S.: Laparoscopic adrenalectomy for cancer. Semin Surg Oncol, 16: 293, 1999 9. Valeri, A., Borrelli, A., Presenti, L., Lucchese, M., Venneri, F.,
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY
10. 11.
12.
13. 14.
15.
Mannelli, M. et al: Adrenal masses in neoplastic patients: the role of laparoscopic procedure. Surg Endosc, 15: 90, 2001 Henry, J. F., Sebag, F., Iacobone, M. and Mirallie, E.: Results of laparoscopic adrenalectomy for large and potentially malignant tumors. World J Surg, 26: 1043, 2002 Kebebew, E., Siperstein, A. E., Clark, O. H. and Duh, Q. Y.: Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms. Arch Surg, 137: 948, 2002 Lombardi, C. P., Raffaelli, M., Boscherini, M., De Crea, C., Alesina, P. F., Traini, E. et al: Laparoscopic adrenalectomy in the treatment of malignant adrenal lesions. Tumori, suppl., 89: 255, 2003 Sarela, A. I., Murphy, I., Coit, D. G. and Conlon, K. C.: Metastasis to the adrenal gland: the emerging role of laparoscopic surgery. Ann Surg Oncol, 10: 1191, 2003 Feliciotti, F., Paganini, A. M., Guerrieri, M., Baldarelli, M., De Sanctis, A., Campagnacci, R. et al: Laparoscopic anterior adrenalectomy for the treatment of adrenal metastases. Surg Laparosc Endosc Percutan Tech, 13: 328, 2003 Kim, J.-H., Ng, C. S., Ramani, A. P., Spaliviero, M., Herts, B., Kaouk, J. et al: Laparoscopic radical adrenalectomy with ad-
16. 17.
18.
19. 20. 21.
525
renal vein tumor thrombectomy: technical considerations. J Urol, 171: 1223, 2004 Luketich, J. D. and Burt, M. E.: Does resection of adrenal metastases from non-small cell lung cancer improve survival? Ann Thorac Surg, 62: 1614, 1996 Lau, W. K., Zincke, H., Lohse, C. M., Cheville, J. C., Weaver, A. L. and Blute, M. L.: Contralateral adrenal metastasis of renal cell carcinoma: treatment, outcome and a review. BJU Int, 91: 775, 2003 Bellantone, R., Ferrante, A., Boscherini, M., Lombardi, C. P., Crucitti, P., Crucitti, F. et al: Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma. Surgery, 122: 1212, 1997 Kim, S. H., Brennan, M. F., Russo, P., Burt, M. E. and Coit, D. G.: The role of surgery in the treatment of clinically isolated adrenal metastasis. Cancer, 82: 389, 1998 Tsivian, A. and Sidi, A. A.: Port site metastases in urological laparoscopic surgery. J Urol, 169: 1213, 2003 Ikramuddin, S., Lucus, J., Ellison, E. C., Schirmer, W. J. and Melvin, W. S.: Detection of aerosolized cells during carbon dioxide laparoscopy. J Gastrointest Surg, 2: 580, 1998
Vol. 173, 519 –525, February 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000149038.89467.30
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY IN 31 PATIENTS ALIREZA MOINZADEH
AND
INDERBIR S. GILL*
From the Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
Purpose: Laparoscopic adrenalectomy for malignancy is controversial. We analyzed our experience with laparoscopic radical adrenalectomy for cancer with an emphasis on predictors of surgical outcome and oncological followup data. Materials and Methods: Since July 1997, 31 patients have undergone a total of 33 laparoscopic adrenalectomies for malignancy. Mean adrenal tumor size was 5 cm (range 1.8 to 9). The laparoscopic approach was transperitoneal in 17 cases, retroperitoneal in 15 and transthoracic in 1. Data were obtained from patient charts, radiographic reports and direct telephone calls to patient families. Results: Associated organ resection (radical nephrectomy) was performed in 3 patients. One case was electively converted to open surgery. There was no operative mortality. The pathological diagnoses were metastatic cancer in 26 cases and primary adrenal malignancy in 7. Current median followup, available on 30 patients, was 26 months (range 1 to 69). Overall 15 patients (48%) died and 16 (52%) were alive, of whom 13 (42%) showed no evidence of disease. Cancer specific survival at a median followup of 42 months was 53% and 5-year actuarial survival was 40%. Local recurrence was noted in 7 patients (23%). There were no port site metastases. Survival was similar in patients with tumors less than 5 cm vs 5 cm or greater. Survival was not associated with patient age, tumor size, operative time or surgical approach. Survival was compromised in patients with local recurrence (p ⫽ 0.016). Conclusions: Laparoscopic radical adrenalectomy can be performed with acceptable outcomes in the carefully selected patient with a small, organ confined, solitary adrenal metastasis or primary adrenal carcinoma. To our knowledge the largest series in the literature to date is presented. KEY WORDS: adrenal glands, laparoscopy, adrenalectomy, neoplasm metastasis, adrenal gland neoplasms
Laparoscopic adrenalectomy has become the gold standard approach for benign surgical adrenal disorders such as aldosteronoma, Cushing’s disease and pheochromocytoma. However, laparoscopic adrenalectomy for solitary metastasis or primary adrenal cancer remains a matter of considerable controversy. Concern rightfully exists over the possibility of carcinomatosis or port site metastasis, as noted in the initial published case reports.1–7 However, recent small series have described laparoscopic adrenalectomy for malignancy with acceptable oncological outcomes.8 –14 Given the controversial nature of this topic, we reviewed our single institution, single surgeon experience with laparoscopic adrenalectomy for malignancy. Perioperative outcomes and oncological followup with a focus on predictors of survival are presented and the relevant literature is reviewed. MATERIALS AND METHODS
Since 1997, we have performed more than 250 laparoscopic adrenalectomies at our institution. Of them 31 patients (33 adrenalectomies) with pathologically confirmed adrenal malignancy were identified retrospectively. The cohort included patients with preoperative suspicion of a solitary metastasis to the adrenal gland and those who were incidentally found to have primary adrenal malignancy. Four additional patients with preoperatively presumed metastasis to the adre-
nal gland malignancy who were found to have benign adenoma on the final pathological report were excluded. Patients who underwent concomitant adrenalectomy during radical nephrectomy for renal cell carcinoma (RCC) were excluded. Selection criteria for the laparoscopic approach were an adrenal mass of 10 cm or less without evidence of peri-adrenal infiltration, caval thrombus or bulky locoregional lymphadenopathy on preoperative computerized tomography (CT). All patients underwent complete preoperative staging, including a detailed history and physical exam, radiographic imaging and endocrine assessment as indicated. Abdominal imaging was primarily 3-dimensional CT with 3 mm adrenal cuts and rarely magnetic resonance imaging or metaiodobenzylguanidine scanning. Followup comprised physical examination, chest x-ray and abdominal/pelvic CT 6 months postoperatively and yearly thereafter at the discretion of the local physician. Patient charts were retrospectively reviewed to establish demographic data. Cancer recurrence and patient survival were determined by a review of radiographic reports (abdominal CT scan/chest x-ray) and chart review. When direct survival data were not current, telephone calls were made to patients or family members by one of us (AM). The diseasefree interval as a predictor of survival was assessed. In patients with a solitary adrenal metastasis the disease-free interval was defined as the time elapsed between treatment of the initial primary cancer and diagnosis of the adrenal mass. Adrenal metastasis discovered within 6 months of treatment of the nonadrenal primary tumor was defined as synchronous, while metastasis discovered more than 6
Submitted for publication June 2, 2004. * Correspondence and requests for reprints: Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic Foundation, 9500 Euclid Ave. A-100, Cleveland, Ohio 44195 (FAX: 216-445-7031; e-mail: [email protected]). 519
520
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY
months later was defined as metachronous. Survival analysis was done using the Kaplan-Meier method with log rank testing for categorical predictors. The Cox regression model was used to assess the association between continuous predictor variables and survival. RESULTS
A total of 33 adrenalectomies were performed in 31 patients. There were 19 males and 12 females with a mean age of 59.8 years (range 38 to 79). Mean tumor size was 5 cm (range 1.8 to 9). No patient had evidence of systemic metastatic disease except 1 patient with diffusely metastatic melanoma who underwent palliative laparoscopic adrenalectomy to minimize the risk of sudden retroperitoneal bleeding, which had occurred in the contralateral adrenal gland. Five patients (16%) underwent preoperative needle biopsy at the referring institution, of which 2 were diagnostic for metastatic disease and 1 was suggestive of the final diagnosis of sarcoma (table 1). The laparoscopic approach used at the discretion of the surgeon (ISG) was transperitoneal in 17 cases, retroperitoneal in 15 and transthoracic in 1. A review of individual operative reports indicated that 4 patients had evidence of local invasion, including to the inferior vena cava and kidney in 1 patient (the only one in this series who was electively converted to open surgery), liver in 1, desmoplastic changes secondary to local infiltration necessitating ipsilateral nephrectomy in 1 and lymph node positive disease in 1 with pheochromocytoma who underwent concomitant radical nephrectomy. One patient with a 5 cm left adrenal mass was intraoperatively detected to have adrenal vein thrombus entering the main left renal vein. Pure laparoscopic techniques were used to occlude the renal artery and vein with a Satinsky clamp, incise the left renal vein, perform en bloc extraction of the venous thrombus along with the adrenal tumor, suture repair the renal vein and revascularize the kidney.15 Pathology reports indicated a diagnosis of adrenal metastasis in 26 patients, primary adrenal cell carcinoma in 6 and malignant pheochromocytoma in 1 (table 1). Surgical margins of the adrenalectomy specimen were negative for cancer in 19 cases (56%), indeterminate in 2 (6%) and positive in 1 (3%). The pathology report made no mention of margin status in 11 patients (33%). Two patients had previously received chemotherapy for the primary malignancy (sarcoma and
TABLE 1. Demographic, operative and pathological data No. pts No. procedures No. gender: Male Female No. side: Lt Rt Bilat No. approach: Transperitoneal Retroperitoneal Transthoracic Mean cm mass size on CT (range) Mean gm specimen wt (range) Mean estimated blood loss (ml) Mean operative time (mins) Hospital stay (days) No. pathological diagnosis: Renal cell Ca metastasis Adrenal cell Ca Colonic metastasis Lung metastasis Metastatic sarcoma Malignant pheochromocytoma Metastatic melanoma NonHodgkin’s lymphoma
31 33
TABLE 2. Overall patient outcome Pt Outcome
No. Pts (%)
No disease evidence Alive with disease Dead of disease Dead of other causes Lost to followup
13 (42) 3 (10) 13 (42) 1 (3) 1 (3)
No. Local Recurrence 1 6
Median Followup (mos) 37 46 17 3 2
lung), while 4 received chemotherapy or immunotherapy after laparoscopic adrenalectomy. There was no operative mortality. Complications occurred in 4 patients (13%), including inferior epigastric injury repaired laparoscopically in 1, atelectasis and fever on day 2 in 1 and port site hernia in 2. Two patients required blood transfusion. In each case adhesions and/or capsular vessels resulted in intraoperative blood loss greater than 500 ml but there was no technical complication. Followup data were available on 30 patients (97%) with an overall median duration of 26 months (table 2). The 5-year Kaplan-Meier survival estimate in the cohort of 30 patients was 40% (see figure). At last followup 16 patients (53%) were alive at a median of 42 months (range 1 to 63). The remaining 14 patients (47%) died at a median of 13 months (range 1 to 29) after the laparoscopic procedure. Of these 14 patients 11 (35%) died of metastatic disease and 3 died of causes unrelated to cancer. Local recurrence was noted in 7 patients (23%), including 3 with metastatic RCC, 2 with metastatic colon cancer and 2 with primary adrenal cortical carcinoma (table 3). In these 7 patients mean adrenal tumor size was 5.5 cm (range 1.8 to 8.6) and the laparoscopic approach was transperitoneal in 4 and retroperitoneal in 3. Mean blood loss was 485 cc (range 100 to 1,200) and mean operative time was 237 minutes (range 175 to 370). Associated organ resection was not performed in any patient. In the 7 patients with local recurrence the final pathology report indicated that the adrenalectomy surgical margin was negative for cancer in 4, indeterminate in 1, positive in 1 and not documented in 1. Six of the 7 patients (86%) with local recurrence died with a median survival of 17 months (range 9 to 52). One patient with metastatic RCC, including bilateral metastatic adrenal masses, had evidence of peritoneal carcinomatosis 7 months after laparoscopic adrenalectomy. Patients with local recurrence had significantly decreased 3-year survival compared to those without local recurrence (16.7% vs 66%, p ⫽ 0.016). Preoperatively cancer of the adrenal gland was suspected in 28 of 31 patients (90%) based on CT findings and clinical history. In the 3 patients who were preoperatively not sus-
19 12 15 14 2 17 15 1 5 (1.8–10) 116 (10–678) 258 181 2.1 13 6 5 4 2 1 1 1
Overall 5-year actuarial plot of survival in all 30 patients in series.
Lt Lt Rt Lt Lt Lt Lt
Rt
Rt
Lt Rt Lt Lt Rt
Side
Transperitoneal Retroperitoneal Transperitoneal Retroperitoneal Retroperitoneal Transperitoneal Transperitoneal Transperitoneal in 4 cases, retroperitoneal in 3
Retroperitoneal Transperitoneal in 3 cases, retroperitoneal in 4
Transperitoneal Transperitoneal Retroperitoneal Retroperitoneal Transperitoneal, converted to open Retroperitoneal
Laparoscopic Approach
175 180 270 195 Not available† 230 370 237
45 202
150
315 290 120 255 240
Operative Time (mins)
100 500 1,200 600 100 600 300 486
25 160
100
200 100 100 100 500
Estimated Blood Loss (cc)
Yes Yes Yes Yes 5
Yes
Yes 7
Yes
Yes Yes Yes Yes Yes
Incomplete
2
Yes Yes
Local recurrence
No local recurrence
Complete
Surgical Resection*
RCC Colon ACC RCC Colon RCC ACC —
ACC —
Lung
RCC RCC Melanoma Colon ACC
Pathological Findings
Neg Not available† Fractured specimen Neg Not available† Neg Neg Neg in 4 cases, not available in 2
Neg Neg in 5 cases, not available in 2
Neg
Not available† Not available† Neg Neg Neg
Surgical Margins
TABLE 3. Patients with resulting mortality or local recurrence
* Subjective surgeon opinion, as documented in operative note. † Not reported on final pathology report with all pathology reports available for review and no data lost.
1.8 7 8.6 8.2 5.1 3.0 5.0 5.5
6—57—M
8—66—M 9—79—F 10—55—M 11—57—M 12—70—M 13—51—M 14—43—F Means or totals—60.1
7
1—60—F 2—68—M 3—40—M 4—72—M 5—70—M
3.6 4.5
2.4 4.2 3 2.5 9
Pt.—Age—Sex No.
7—57—F Means or totals—60.6
CT Tumor Size (cm)
Yes Yes Yes Yes Yes Yes Yes Yes in 7 cases
No No in 7 cases
No
No No No No No
Local Recurrence
52 13 25 9 13 21 Alive with disease 22.1
17 17.7
4
48 26 2 26 1
Time to Death (mos)
Lung, liver Rt adrenal metastases Lung Peritoneal carcinomatosis Lung Brain, spine Retroperitoneum —
Lung, liver metastases at laparoscopic adrenalectomy Lung, liver —
Brain Lung, brain Pelvic bone, brain Not available Not available
Metastatic Sites ⫹ Comments
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY
521
522
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY TABLE 4. Patients with adrenal tumors less than 5 vs 5 cm or greater Tumor Size (cm) Less Than 5
5 or Greater
p Value
No. pts 17 16 — No. men (%) 12 (71) 8 (50) 0.23 (chi-square test) No. rt side (%) 6 (35) 10 (63) 0.12 (chi-square test) Mean tumor size (cm) 3.1 6.6 ⬍0.001 (t test) No. transperitoneal approach (%) 10 (65) 6 (38) 0.87 (chi-square test) Median estimated blood loss (cc) 175 300 0.15 (t test) Mean operative time (mins) 192 207 0.62 (t test) No. operative resection: 0.07 (exact unconditional test) Complete 17 13 Incomplete 0 3 Median hospital stay (days) 1.0 2.0 0.15 (t test) No. pathological findings (%): 0.17 (exact unconditional test) Metastasis 15 (88) 11 (69) Primary 2 (12) 5 (31) No. surgical pathological margins: 0.72 (chi-square test) Pos 0 1 Neg 9 10 Indeterminate 1 1 Not documented on final pathology report 7 4 No. local recurrence (%) 2 (12) 5 (31) 0.17 (exact unconditional test) Median specimen wt (gm) 28 78 0.07 (Mann-Whitney test) No. alive at last followup/total no. (%) 9/16 (56) 8/15 (53) 0.87 (chi-square test) Mean followup (mos) 33.4 21 0.11 (t test) The 2 groups were compared on binary variables using the chi-square or exact unconditional test, on normally distributed continuous variables using the t test and on nonnormally distributed continuous variables using the Mann-Whitney test.
pected of having malignant adrenal disease the final pathology report identified adrenocortical carcinoma (ACC) in 2 and nonHodgkin’s lymphoma in 1. Six of the 26 patients with adrenal metastasis had synchronous and 19 had metachronous disease with data not available on 1. There was no difference in survival between the synchronous and metachronous groups (log rank test p ⫽ 0.96). Survival was not associated with gender (p ⫽ 0.11), age (p ⫽ 0.36), tumor size (p ⫽ 0.14), tumor side (p ⫽ 0.54), estimated blood loss (p ⫽ 0.41), specimen weight (p ⫽ 0.71), operative time (p ⫽ 0.68) or transperitoneal vs retroperitoneal laparoscopic surgical approach (p ⫽ 0.11). There was no survival difference in patients with solitary metastasis to the adrenal gland compared to those with primary adrenal malignancy (log rank test p ⫽ 0.99). Five-year survival was similar in patients with an adrenal tumor of less than 5 vs 5 cm or greater (36% vs 46%, p ⫽ 0.43, table 4). Since RCC comprised 13 of the 26 metastatic cases (50%), we performed a comparison of survival between the RCC, ACC, colon cancer and lung cancer groups, and found no survival difference (log rank test p ⫽ 0.28). DISCUSSION
The rationale for surgical excision of solitary adrenal metastases has previously been addressed. In general the prognosis of patients with metastatic disease is poor with few survivors at 5 years. In regard to nonsmall cell lung cancer Luketich and Burt reported on 14 patients with isolated adrenal metastasis from lung cancer.16 Median survival in the open surgical resection plus chemotherapy group of 6 patients was greater than in the chemotherapy alone group of 6 (31 vs 8.5 months, p ⫽ 0.03). In our series 4 patients with adrenal metastasis from lung cancer had an overall median followup of 25 months, of whom 2 are currently alive without evidence of disease. In regard to RCC Lau et al reported on 11 patients undergoing contralateral open surgical resection for adrenalectomy for metastasis and reviewed the literature.17 In 20 publications 27 of 56 patients (48%) were alive at last followup (range 0.3 to 14.3 years). Heniford et al identified 38 cases of synchronous or metachronous contralateral adrenal metastasis from RCC in the literature.8 A total of 35 patients underwent laparoscopic or open resection of adrenal metastasis with 62% having no evidence of disease at an average
followup of 26 months. In our series 6 of the 13 patients (46%) with metastatic RCC were alive at a median followup of 39 months. In regard to primary ACC overall 5-year survival after open surgery has been reported to be 25%. Five-year survival increases to almost 50% if complete resection is achieved at the time of curative surgery. In the series of Henry et al 5 of 6 patients were disease-free at a median followup of 27.5 months.10 In a report of 179 patients undergoing open adrenalectomy for ACC Bellantone et al documented local recurrence in 52 (37%).18 Our 33% incidence of local recurrence for ACC compares favorably with this open surgery experience. Three of the 6 patients (50%) with ACC in our series were alive at a median followup of 21 months, including 2 without evidence of disease and 1 undergoing chemotherapy. In our series overall 5-year actuarial survival was 40% at a median followup of 26 months. These results compare favorably with those in a prior open series from Memorial SloanKettering Cancer Center (MSKCC).19 In the MSKCC report 37 patients undergoing open adrenalectomy for nonprimary adrenal malignancy were found to have a 5-year actuarial survival of 24% with a median survival of 21 months. The MSKCC series also documented improved survival when the pre-adrenalectomy disease-free interval was greater than 6 months,13, 19 a finding that was not confirmed by our data. A possible explanation is the different distribution of the nonadrenal primary malignancy in these series. In the 2 MSKCC reports a lung primary tumor was present in 46% and 56% of patients, respectively. In our cohort lung cancer comprised only 15% of cases, while RCC comprised 50%. If one believes that the disease-free interval is a surrogate for the intrinsic biological aggressiveness of the primary tumor and recognizes that RCC may lead to metastasis years after resection of the renal primary lesion, it is plausible to accept the differences between these 2 series in regard to the diseasefree interval. An objective of our study was to identify potential predictors of survival in this patient population. On univariate analysis age, gender, specimen weight, estimated blood loss, operative time and tumor size/side were not found to have prognostic significance in regard to patient survival. Similarly patients with an adrenal tumor of less than 5 cm compared to those with a tumor of 5 cm or greater had compa-
Final reoperation
ACC
Hofle et al3
Local, carcinomatosis
4
Uncomplicated
Not available
43 F Lt 3 Cushing’s syndrome
Hamoir et al4
Deckers et al5
Transperitoneal
74 M Rt 2.7 Conn’s syndrome
Carcinomatosis
6
Foxius et al6
Benign
Local, carcinomatosis
6
Uncomplicated
Transperitoneal
74 M Rt 2.7 Conn’s syndrome
Chen et al7
Nonsmall cell lung Ca
Carcinomatosis including port site recurrence
Intraop mass had increased to 8 ⫻ 6 cm, specimen removed intact in entrapment sack 5
Transperitoneal
55 F Lt 2.5 Nonsmall cell lung Ca
Same features as initial tumor Identical to initial tumor, Nonsmall cell lung Ca with increased cellularity ⫹ deemed ACC based on necrosis consistent with clinical metastasis ACC
Benign
Carcinomatosis
10
“Difficult ⫹ bloody,” con- Partial adrenalectomy version to open procedure
25 F Rt 12 Secondary amenorrhea ⫹ virilization Not available
Poorly differentiated lung “Undetermined” malignant Benign Ca potential Poorly differentiated lung Could not confirm ACC due ACC Ca to fragmented tumor
“Multiple metastases”
Local, carcinomatosis
Pathological findings: Initial specimen Benign adenoma
8
14
Conversion to open surgery, en bloc removal of part of kidney
Uncomplicated
Time to recurrence (mos) Recurrence site
Not available
Not available
Laparoscopic approach Surgery comment
62 M Lt 5.5 Lung adenoca
50 F Lt 5 Cushing’s syndrome
Pt age Sex Side Tumor size (cm) History
Suzuki et al2
TABLE 5. Literature review of single case reports questioning laparoscopic adrenalectomy safety in setting of malignancy
Ushiyama et al1
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY
523
524
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY TABLE 6. Literature review of series of laparoscopic adrenalectomy for cancer References
No. Pts
Heniford et al8 Valeri et al9 Henry et al10 Kebebew et al11
11 6 6 18
Lombardi et al12
9
Sarela et
al13
11
Followup (mos)
Comments
Mean 8.3 Mean 8.6 Median 27.5 Mean 39.6 Mean 17 Median 21
6 Mean 19.5 in 2 pts who died ⫹ 7 in 4 survivors Feliciotti et al14 Present series 31 Median 26 Only series with 5 or more patients are included.
rable overall outcomes and survival at a followup of 33.4 and 21 months, respectively (table 4). In the last few years 7 initial case reports questioned the adequacy of the laparoscopic approach for malignant adrenal tumors (table 5).1– 6 Briefly, these 7 reports of a single patient each described locally recurrent malignancy shortly after laparoscopic adrenalectomy, that is within 4 to 14 months. Two of these 7 patients had a lung primary lesion metastatic to the adrenal gland. The remaining 5 cases, initially thought to be benign, were only later diagnosed by final histopathological findings as adrenocortical carcinoma. Laparoscopy was hypothesized to have potentially had a role in tumor dissemination in each case. However, no clear evidence as such was provided with minimal discussion about the central issues of the innate aggressive nature of the tumor or details about the adequacy of the laparoscopic technique used. More recently a few series of a limited number of patients undergoing laparoscopic adrenalectomy for malignancy have been reported (table 6).8 –14 Although the number of patients in each individual series was small and followup was short, certain inferences can be drawn. In the 100 aggregate patients in these 8 series, including ours, only 1 had carcinomatosis and no port site recurrences were reported. This stands in stark contrast to the 100% incidence of carcinomatosis and/or port site recurrence documented in single case reports (table 5). This wide discrepancy in outcomes between individual case reports and patient series raises suspicion about the technical adequacy of laparoscopic techniques among institutions (tables 5 and 6). Additionally, the inherent nature of malignancy may vary similarly. Port site metastasis is a rare occurrence in urological laparoscopy. In a recent review of more than 2,000 cases of laparoscopic oncological surgery Tsivian and Sidi reported 11 (0.6%) of port site metastasis.20 Based on this review they concluded that factors contributing to port site metastasis include biological tumor aggressiveness, surgical violation of the tumor boundary, not using a specimen extraction sack and ascites. With proper patient selection and adherence to meticulous, skilled laparoscopic technique the majority of port site metastases can be avoided. Carcinomatosis has been hypothesized possibly to occur from the dispersion of malignant cells by carbon dioxide gas, tumor spillage due to inadvertent violation of the involved organ, extraction site contamination by tumor cells and the questionable immunosuppressive effect of pneumoperitoneum. In clinical studies Ikramuddin et al used a saline trap intraoperatively to capture effluent CO2 in 35 patients undergoing elective laparoscopic procedures.21 Although 15 patients had malignancies, only 2 were found to have malignant cells in the effluent. These 2 patients had preexisting carcinomatosis. As such, Ikramuddin et al concluded that it was unlikely that cell aerosolization was a significant contributor to port site metastasis. Currently our main adrenal specific contraindication to lapa-
10/11 Pts (91%) disease-free 3/6 Pts (50%) disease-free All pts with ACC, 5/6 (93%) disease-free 9/13 Pts (69%) with metastatic disease to adrenal gland ⫹ 2/5 (40%) with primary ACC disease-free 9/11 Pts (82%) disease-free, 1 dead of unrelated cause About 60% survival, 11 laparoscopic vs 20 open radical adrenalectomies showed no difference in overall survival 4/6 Pts (67%) disease-free 13/31 Pts (42%) disease-free
roscopic adrenalectomy is an irregular adrenal mass with periadrenal infiltration, as noted on 3-dimensional CT with 3 mm adrenal cuts, which is our preferred imaging modality. For surgeons with advanced laparoscopic experience size per se is a less important issue, although we generally limit laparoscopic adrenalectomy to tumors in the 10 cm range. Intraoperative concern regarding the adequacy of wide excision should prompt the consideration of open conversion. CONCLUSIONS
At intermediate term followup our local recurrence and cancer specific survival rates following laparoscopic adrenalectomy for cancer appear to be in concordance with those of published open series. Along with other recent publications this report suggests that in the carefully selected patient with a small, organ confined adrenal malignancy laparoscopic radical adrenalectomy is safe and efficacious. Since local recurrence is associated with a poor prognosis, complete en bloc excision is important. If concerns exist regarding the adequacy of wide margin dissection, the threshold for open conversion should be low. Meng Xu provided statistical analyses and support. REFERENCES
1. Ushiyama, T., Suzuki, K., Kageyama, S., Fujita, K., Oki, Y. and Yoshimi, T.: A case of Cushing’s syndrome due to adrenocortical carcinoma with recurrence 19 months after laparoscopic adrenalectomy. J Urol, 157: 2239, 1997 2. Suzuki, K., Ushiyama, T., Mugiya, S., Kageyama, S., Saisu, K. and Fujita, K.: Hazards of laparoscopic adrenalectomy in patients with adrenal malignancy. J Urol, 158: 2227, 1997 3. Hofle, G., Gasser, R. W., Lhotta, K., Janetschek, G., Kreczy, A. and Finkenstedt, G.: Adrenocortical carcinoma evolving after diagnosis of preclinical Cushing’s syndrome in an adrenal incidentaloma. A case report. Hormone Res, 50: 237, 1998 4. Hamoir, E., Meurisse, M. and Defechereux, T.: Is laparoscopic resection of a malignant corticoadrenaloma feasible? Case report of early, diffuse and massive peritoneal recurrence after attempted laparoscopic resection. Ann Chir, 52: 364, 1998 5. Deckers, S., Derdelinckx, L., Col, V., Hamels, J. and Maiter, D.: Peritoneal carcinomatosis following laparoscopic resection of an adrenocortical tumor causing primary hyperaldosteronism. Horm Res, 52: 97, 1999 6. Foxius, A., Ramboux, A., Lefebvre, Y., Broze, B., Hamels, J. and Squifflet, J.: Hazards of laparoscopic adrenalectomy for Conn’s adenoma. When enthusiasm turns to tragedy. Surg Endosc, 13: 715, 1999 7. Chen, B., Zhou, M., Cappelli, M. C. and Wolf, J. S., Jr.: Port site, retroperitoneal and intra-abdominal recurrence after laparoscopic adrenalectomy for apparently isolated metastasis. J Urol, 168: 2528, 2002 8. Heniford, B. T., Arca, M. J., Walsh, R. M. and Gill, I. S.: Laparoscopic adrenalectomy for cancer. Semin Surg Oncol, 16: 293, 1999 9. Valeri, A., Borrelli, A., Presenti, L., Lucchese, M., Venneri, F.,
LAPAROSCOPIC RADICAL ADRENALECTOMY FOR MALIGNANCY
10. 11.
12.
13. 14.
15.
Mannelli, M. et al: Adrenal masses in neoplastic patients: the role of laparoscopic procedure. Surg Endosc, 15: 90, 2001 Henry, J. F., Sebag, F., Iacobone, M. and Mirallie, E.: Results of laparoscopic adrenalectomy for large and potentially malignant tumors. World J Surg, 26: 1043, 2002 Kebebew, E., Siperstein, A. E., Clark, O. H. and Duh, Q. Y.: Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms. Arch Surg, 137: 948, 2002 Lombardi, C. P., Raffaelli, M., Boscherini, M., De Crea, C., Alesina, P. F., Traini, E. et al: Laparoscopic adrenalectomy in the treatment of malignant adrenal lesions. Tumori, suppl., 89: 255, 2003 Sarela, A. I., Murphy, I., Coit, D. G. and Conlon, K. C.: Metastasis to the adrenal gland: the emerging role of laparoscopic surgery. Ann Surg Oncol, 10: 1191, 2003 Feliciotti, F., Paganini, A. M., Guerrieri, M., Baldarelli, M., De Sanctis, A., Campagnacci, R. et al: Laparoscopic anterior adrenalectomy for the treatment of adrenal metastases. Surg Laparosc Endosc Percutan Tech, 13: 328, 2003 Kim, J.-H., Ng, C. S., Ramani, A. P., Spaliviero, M., Herts, B., Kaouk, J. et al: Laparoscopic radical adrenalectomy with ad-
16. 17.
18.
19. 20. 21.
525
renal vein tumor thrombectomy: technical considerations. J Urol, 171: 1223, 2004 Luketich, J. D. and Burt, M. E.: Does resection of adrenal metastases from non-small cell lung cancer improve survival? Ann Thorac Surg, 62: 1614, 1996 Lau, W. K., Zincke, H., Lohse, C. M., Cheville, J. C., Weaver, A. L. and Blute, M. L.: Contralateral adrenal metastasis of renal cell carcinoma: treatment, outcome and a review. BJU Int, 91: 775, 2003 Bellantone, R., Ferrante, A., Boscherini, M., Lombardi, C. P., Crucitti, P., Crucitti, F. et al: Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma. Surgery, 122: 1212, 1997 Kim, S. H., Brennan, M. F., Russo, P., Burt, M. E. and Coit, D. G.: The role of surgery in the treatment of clinically isolated adrenal metastasis. Cancer, 82: 389, 1998 Tsivian, A. and Sidi, A. A.: Port site metastases in urological laparoscopic surgery. J Urol, 169: 1213, 2003 Ikramuddin, S., Lucus, J., Ellison, E. C., Schirmer, W. J. and Melvin, W. S.: Detection of aerosolized cells during carbon dioxide laparoscopy. J Gastrointest Surg, 2: 580, 1998