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Asian J Endosc Surg ISSN 1758-5902
O R I G I N A L A RT I C L E
Laparoscopic adrenalectomy for metastatic adrenal tumor Takahiro Hirayama, Tetsuo Fujita, Dai Koguchi, Morihiro Nishi, Shinji Kurosaka, Hideyasu Tsumura, Ken-ichi Tabata & Masatsugu Iwamura Department of Urology, Kitasato University School of Medicine, Sagamihara, Japan
Keywords Laparoscopic adrenalectomy; metastasis; survival Correspondence Takahiro Hirayama, Department of Urology, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan. Tel: +81 42 778 9091 Fax: +81 42 778 9374 Email: [email protected] Received: 3 July 2013; revised 22 September 2013; accepted 2 October 2013 DOI:10.1111/ases.12076
Abstract Introduction: Treating adrenal metastases from primary malignancies with laparoscopic adrenalectomy (LA) remains controversial. The aim of this study was to evaluate the feasibility, effectiveness and efficiency of LA for solitary adrenal metastasis. Methods: From November 2003 to September 2012, eight consecutive patients with adrenal metastasis were treated with LA. A retrospective study was conducted, and clinical and histological data were analyzed. Results: All LA were successfully performed. There were no major complications, blood transfusions or conversions to open adrenalectomy. The patients included seven men and one woman with a median age of 59 years at the time of operation. Adrenal metastases were most commonly noted to be from non-small-cell lung cancer (four patients) and renal cell carcinoma (four patients). The majority of adrenal metastases were unilateral (right: one patient; left: seven patients). One patient had bilateral metastases. The median overall survival was 14 months. Four patients (two with non-small-cell lung cancer; two with renal cell carcinoma) were alive with no evidence of metastatic disease as of October 2013. Conclusion: LA is a safe and effective procedure for patients with isolated metastases. Surgical resection with LA for a solitary adrenal metastasis from primary malignancy can achieve a good prognosis.
Introduction The development of minimally invasive surgical techniques has revolutionized many surgical procedures. Compared with traditional open surgery, the laparoscopic approach to major abdominal operations reduces organ system impairment, resulting in significantly less perioperative morbidity and recovery time (1). Since Gagner et al. reported their first laparoscopic adrenalectomy (LA) in 1992 (2), this minimally invasive approach has become the gold standard for removing benign lesions of the adrenal gland. However, applying LA for a solitary metastasis or primary adrenal carcinoma remains controversial because port-site metastasis or dissemination has been reported after LA for adrenal malignancies (3,4). Whereas primary adrenal carcinoma is a locoregionally aggressive disease, adrenal metastasis is often confined within the adrenal capsule, offering more
opportunities to obtain en bloc adrenalectomy. Therefore, some investigators recommend LA as an appropriate initial approach for a solitary adrenal metastasis (5,6). Thus, in the current study, we evaluate the feasibility, effectiveness and efficiency of LA for solitary adrenal metastases in eight consecutive patients.
Patients and Methods A retrospective single center study was conducted by analyzing the records of consecutive patients who underwent adrenalectomy for a solitary adrenal metastasis. From November 2003 to September 2012, nine adrenalectomies were performed in eight patients to treat adrenal metastasis at our institution (Kitasato University School of Medicine, Sagamihara, Japan). Bilateral diseases were counted as two adrenalectomies for one
Asian J Endosc Surg 7 (2014) 43–47 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
43
LA for adrenal metastasis
T Hirayama et al.
Table 1 Patient characteristics, and perioperative and postoperative data
Age Patient (years) Gender Side 1 2 3 4 5 6† 7 8 Median
56 59 48 61 57 59 77 71 59
M M M M F M M M
Lt. Lt. Lt. Lt. Rt. Bilateral Lt. Lt.
PM
Treatment for PM
NSCLC NSCLC NSCLC NSCLC Lt. RCC Lt. RCC Lt. RCC Rt. RCC
Surgery Chemotherapy Chemotherapy Surgery Surgery Surgery Surgery Surgery
Interval to diagnosis to AM Metastasi EBL Operative Hospital Survival (months) s size (mm) (mL) time (min) stay (days) (months) Status 24.0 31.0 25.0 11.0 70.0 73.0 52.0 61.0 41.5
82 30 50 70 50 75 30 86 60
20 40 NR NR 10 120 20 50 30
220.0 140.0 195.0 285.0 163.0 120.0 125.0 150.0 156.5
6.0 4.0 5.0 7.0 12.0 10.0 3.0 5.0 5.5
9 69 7 8 33 93 19 7 14
NEMD NEMD Dead due to PM Dead due to PM Dead due to PM Recurrence, but alive NEMD NEMD
†LA was performed for only one side and open surgery was performed for the other. AM, adrenal metastasis; EBL, estimated blood loss; F, female; LA, laparoscopic adrenalectomy; Lt., Left; M, male; NEMD, no evidence of metastatic disease; NR, not reported; NSCLC, non-small-cell lung cancer; PM, primary malignancy; RCC, renal cell carcinoma; Rt., Right.
patient. CT was used to diagnose solitary adrenal metastasis in all patients, and there was no evidence of extra-adrenal metastasis. Metastases discovered within 6 months of a previous treatment for primary malignancy were considered synchronous, and those discovered after 6 months were designated as metachronous. No percutaneous adrenal biopsy was performed for the diagnosis of malignancy. For all eight patients, LA was performed via a transperitoneal approach. Adrenal glands with surrounding fat were resected with the greatest of care to prevent tumor disruption. Specimens were extracted intact within a bag. After surgery, the patients were followed up every 3 months by physical examination and systemic CT. Survival was defined as the time between LA and death or last follow-up visit. The status (dead or alive) of each patient was obtained from hospital records.
Results Patients’ characteristics and perioperative and postoperative data are summarized in Table 1. The patients included seven men and one woman with a median age of 59 years (range, 48–77 years) at the time of operation. All LA were performed successfully. There were no major complications, blood transfusions or conversions to open adrenalectomy. All adrenal metastases were found without intensive adhesion to peri-adrenal structures and removed safely without capsular disruption. Renal cell carcinoma (RCC) was the most common primary malignancy (five adrenalectomies in four patients), followed by non-small-cell lung cancer (NSCLC) (four adrenalectomies in four patients). The majority of adrenal metastases were unilateral (right: one patient;
44
left: six patients); only one patient had bilateral metastases. Two patients received adrenalectomy on the same side as a previous nephrectomy. The patient with bilateral adrenal metastases from RCC underwent simultaneous procedures: (i) open adrenalectomy for adrenal metastasis on the same side as a previous open nephrectomy for RCC with a horseshoe kidney and (ii) LA for the other side of the adrenal metastasis (Figure 1a). Another patient who had undergone a previous laparoscopic nephrectomy underwent LA to remove the adrenal metastasis on the same side as the primary tumor (Figure 1b). All adrenal metastases were identified as metachronous metastasis over a median duration of 41.5 months after the detection of primary malignancies. Median tumor size was 60 mm (range, 30–86 mm), median operative time was 156.5 min (range, 120.0– 285.0), and median estimated blood loss was 30 mL (range, 10–120 mL). Median postoperative hospital stay was 5.5 days (range, 3.0–12.0 days). For two patients treated with substitution doses of glucocorticoids after surgery, hospital stay was more than 10.0 days. In all cases, pathological examinations revealed the diagnosis of metastasis related to primary malignancies. No local or port-site recurrence was observed during follow-up period. Median overall survival was 14 months (range, 7–93 months). Three patients, including two with metastases from NSCLC and one with metastasis from RCC, died from distant metastasis of other organs. Five patients were alive as of October 2013. Four patients, two with NSCLC and two with RCC, were alive with no evidence of metastatic disease. The longest survival (93 months) was observed in a male patient with primary malignancy of RCC with a horseshoe kidney. He had a pancreas metastasis 70 months after bilateral adrenalectomies and was treated with molecular-targeted therapy.
Asian J Endosc Surg 7 (2014) 43–47 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
LA for adrenal metastasis
T Hirayama et al.
Figure 1 Unenhanced CT images of the upper abdomen. (a) A 59-year-old male patient with bilateral adrenal metastases from RCC with a horseshoe kidney (arrows). Open adrenalectomy for adrenal metastasis on the same side as a previous open nephrectomy and LA for the other side of the adrenal metastasis were performed simultaneously. (b) A 77-year-old male patient with left adrenal metastasis from RCC (arrow). LA for adrenal metastasis on the same side as a previous laparoscopic nephrectomy was performed. LA, laparoscopic adrenalectomy; RCC, renal cell carcinoma
Discussion The adrenal gland is a frequent site of metastasis from various malignancies because of the gland’s rich sinusoidal blood flow and the multiple pathways of arterial blood supply (7). In Western countries, lung and breast cancers account for most adrenal metastases, followed by melanoma, hepatocarcinoma and renal cancer (8). Also, Lam and Lo reported that, in Hong Kong, lung cancer is the most common primary malignancy, followed by stomach and esophageal cancers (9). Ma et al. reported that the two most common sites of primary tumor were the kidney and lung, and these accounted for more than half of all cases of cancer in China (10). In the current study, adrenal metastases were most commonly noted to be from lung and kidney cancers (four of eight patients). According to autopsy-based reviews, adrenal metastases were found in 10%–27% of patients with malignancies, but isolated adrenal metastases were extremely rare (11,12). Lee et al. reported that only 4 of 1715 patients (0.2%) with extra-adrenal cancer had solitary adrenal metastasis at the first evaluation (12). As most adrenal metastases have smooth borders and do not invade neighboring organs, unenhanced CT is useful for detecting adrenal masses; it has a sensitivity of 72% and a specificity of 98% (13). Percutaneous biopsy also has a diagnostic value for adrenal metastasis. An ex vivo study with core biopsies of the adrenal gland showed a positive predictive value of 100% and a negative predictive value of 92% for the diagnosis of malignancy (14). However, complications associated with biopsy were also reported, with complication rates ranging from 3% to 13% (15). These complications include hematoma, pancreatitis, pneumothorax, retroperitoneal abscess and tumor recurrence along the needle track. Thus, in the current study, we did not perform
percutaneous biopsy in any patients in order to prevent tumor seeding. Surgical resection of adrenal metastases was first performed more than 30 years ago (16). Since then, many patients have benefited from surgical resection, and longtime survival can be achieved. Five-year or more survival after adrenalectomy has often been reported for various primary malignancies (Table 2) (17–25). In the current series, median survival after adrenalectomy was 14 months, and survival after 5 years was noted in two patients, one with RCC and one with NSCLC. Tumor type has been suggested to be a prognostic factor (10). Ma et al. reported that patients with RCC had the best survival rates, whereas patients with NSCLC had the worst survival rates (10). Zerrweck et al. showed that patients who presented with a nonrenal cancer had an increased mortality risk of almost fourfold compared to patients with RCC (26). In contrast, an acceptable survival rate was shown in a large series of patients with NSCLC treated at MD Anderson Cancer Center (Houston, USA) (25). Metachronous metastases also have a better survival rate, especially in patients with RCC (10). In the current study, all adrenal metastases were found to be metachronous. Synchronous lesions may be more aggressive and may grow faster than metachronous lesions. The difference in survival rates may be attributed to the intrinsic biological behavior of tumor types. Compared with open adrenalectomy, the benefits of LA are widely accepted with respect to analgesic use, return of functional status and perioperative outcome (1,27). LA has become the gold standard treatment for benign adrenal masses. However, LA for adrenal metastasis is still considered controversial, given that its technical challenges require advanced laparoscopic expertise. During our study, eight patients safely underwent LA for metastasis with a median size of 60 mm (range, 30–86 mm). No tumor disruption or major perioperative
Asian J Endosc Surg 7 (2014) 43–47 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
45
LA for adrenal metastasis
T Hirayama et al.
Table 2 Published series of adrenalectomies for metastatic disease from RCC or NSCLC Survival (months) Mean
Median
Long-term survivors (month)†
Selected series of adrenalectomies for adrenal metastases from NSCLC Lucchi et al. (17) 2005 10 80 Pfannshchmidt et al. (18) 2005 11 70 Strong et al. (19) 2007 29 127 Present study 2013 4 69
31 12.6 29 23
NR NR NR 8.5
10% 10% 22% 25%
Selected series of adrenalectomies for adrenal metastases from RCC Lau et al. (20) 2003 11 120 Siemer et al. (21) 2004 56 120 Antonelli et al. (22) 2006 48 142 Bahrami et al. (23) 2009 19 180 Present study 2013 4 93
48 20 99 NR 38
NR NR NR NR 26
20% 19.6% 24% 25% 25%
Author
Year
n
Maximum survival (months)
†More than 60 months. NR, not reported; NSCLC, non-small-cell lung cancer; RCC, renal cell carcinoma.
complication occurred, and four patients are still alive with no evidence of metastatic disease. Although the routine use for LA is usually limited to masses smaller than 60 mm (28), Nguyen et al. reported that large tumor size was not considered a contraindication for LA, even with metastases (29). Sancho et al. showed that metastasis size does not appear to have any influence on survival (15). However, all adrenal metastases should be removed under strict oncologic principals, including avoidance of tumor disruption and wide resection with an adequate margin (24,26). Although several investigators have reported that adrenal metastasis offers more opportunities to obtain en bloc adrenalectomy because it is often confined within the adrenal capsule, conversion to open adrenalectomy from laparoscopic surgery should not be delayed if an oncological resection cannot be performed (5,6). According to our current series, LA can be tackled successfully and safely by means of laparoscopy. Moreover, it is accepted that surgical resection with LA for a solitary adrenal metastasis from primary malignancy can achieve a good prognosis. It should be emphasized that there have been very few series of LA for metastases, and the limitations of retrospective studies are obvious. The small number of patients with isolated adrenal metastasis hinders performance of randomized and prospective studies, necessitating additional research and pooled analysis to confirm the validity of the current study. However, our study will be meaningful for those considering this surgical approach to remove adrenal metastases.
Acknowledgment The authors have no conflict of interest to report.
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References 1. Korman JE, Ho T, Hiatt JR et al. Comparison of laparoscopic and open adrenalectomy. Am Surg 1997; 63: 908– 912. 2. Gagner M, Lacroix A, Bolté E. Laparoscopic adrenalectomy in Cushing’s syndrome and pheochromocytoma. N Engl J Med 1992; 327: 1033. 3. Suzuki K, Ushiyama T, Mugiya S et al. Hazards of laparoscopic adrenalectomy in patients with adrenal malignancy. J Urol 1997; 158: 2227. 4. Castillo OA, Vitagliano G, Kerkebe M et al. Laparoscopic adrenalectomy for suspected metastasis of adrenal glands: Our experience. Urology 2007; 69: 637–641. 5. Kim SH, Brennan MF, Russo P et al. The role of surgery in the treatment of clinically isolated adrenal metastasis. Cancer 1998; 82: 389–394. 6. Moinzadeh A & Gill IS. Laparoscopic radical adrenalectomy for malignancy in 31 patients. J Urol 2005; 173: 519– 525. 7. Uberoi J & Munver R. Surgical management of metastases to the adrenal gland: Open, laparoscopic, and ablative approaches. Curr Urol Rep 2009; 10: 67–72. 8. Gittens PR Jr, Solish AF, Trabulsi EJ et al. Surgical management of metastatic disease to the adrenal gland. Semin Oncol 2008; 35: 172–176. 9. Lam KY & Lo CY. Metastatic tumours of the adrenal glands: A 30-year experience in a teaching hospital. Clin Endocrinol (Oxf) 2002; 56: 95–101. 10. Ma X, Li H, Zhang X et al. Modified anatomical retroperitoneoscopic adrenalectomy for adrenal metastatic tumor: Technique and survival analysis. Surg Endosc 2013; 27: 992–999. 11. Bullock WK & Hirst AE Jr. Metastatic carcinoma of the adrenal. Am J Med Sci 1953; 226: 521–524. 12. Lee JE, Evans DB, Sherman SI et al. Evaluation of the incidental adrenal mass. Am J Med 1997; 103: 249–250.
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13. Boland GW, Lee MJ, Gazelle GS et al. Characterization of adrenal masses using unenhanced CT: An analysis of the CT literature. AJR Am J Roentgenol 1998; 171: 201–204. 14. Saeger W, Fassnacht M, Chita R et al. High diagnostic accuracy of adrenal core biopsy: Results of the German and Austrian adrenal network multicenter trial in 220 consecutive patients. Hum Pathol 2003; 34: 180–186. 15. Sancho JJ, Triponez F, Montet X et al. Surgical management of adrenal metastases. Langenbecks Arch Surg 2012; 397: 179– 194. 16. Twomey P, Montgomery C, Montet X et al. Successful treatment of adrenal metastases from large-cell carcinoma of the lung. JAMA 1982; 248: 581–583. 17. Lucchi M, Dini P, Ambroqi MC et al. Metachronous adrenal masses in resected non-small cell lung cancer patients: Therapeutic implications of laparoscopic adrenalectomy. Eur J Cardiothorac Surg 2005; 27: 753–756. 18. Pfannschmidt J, Schlolaut B, Ambroqi MC et al. Adrenalectomy for solitary adrenal metastases from nonsmall cell lung cancer. Lung Cancer 2005; 49: 203–207. 19. Strong VE, D’Angelica M, Tang L et al. Laparoscopic adrenalectomy for isolated adrenal metastasis. Ann Surg Oncol 2007; 14: 3392–3400. 20. Lau WK, Zincke H, Lohse CM et al. Contralateral adrenal metastasis of renal cell carcinoma: Treatment, outcome and a review. BJU Int 2003; 91: 775–779. 21. Siemer S, Lehmann J, Lohse CM et al. Adrenal metastases in 1635 patients with renal cell carcinoma: Outcome and
22.
23.
24.
25.
26.
27.
28.
29.
indication for adrenalectomy. J Urol 2004; 171: 2155–2159. discussion 2159. Antonelli A, Cozzoli A, Simeone C et al. Surgical treatment of adrenal metastasis from renal cell carcinoma: A singlecentre experience of 45 patients. BJU Int 2006; 97: 505–508. Bahrami A, Truong LD, Shen SS et al. Synchronous renal and adrenal masses: An analysis of 80 cases. Ann Diagn Pathol 2009; 13: 9–15. Gagner M, Pomp A, Heniford BT et al. Laparoscopic adrenalectomy: Lessons learned from 100 consecutive procedures. Ann Surg 1997; 226: 238–246. Landry CS, Perrier ND, Karp DD et al. Outcome of patients with adrenal metastasis from lung cancer: Selection criteria for surgery. J Clin Oncol 2010; 28: 15 (suppl)): e18071. Zerrweck C, Caiazzo R, Clerquin B et al. Renal origin and size are independent predictors of survival after surgery for adrenal metastasis. Ann Surg Oncol 2012; 19: 3621–3626. Gonzalez R, Smith CD, McClusky DA 3rd et al. Laparoscopic approach reduces likelihood of perioperative complications in patients undergoing adrenalectomy. Am Surg 2004; 70: 668–674. Mittendorf EA, Lim SJ, Schacherer CW et al. Melanoma adrenal metastasis: Natural history and surgical management. Am J Surg 2008; 195: 363–368. discussion 368– 9. Nguyen PH, Keller JE, Novitsky YW et al. Laparoscopic approach to adrenalectomy: Review of perioperative outcomes in a single center. Am Surg 2011; 77: 592–596.
Asian J Endosc Surg 7 (2014) 43–47 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
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Asian J Endosc Surg ISSN 1758-5902
O R I G I N A L A RT I C L E
Laparoscopic adrenalectomy for metastatic adrenal tumor Takahiro Hirayama, Tetsuo Fujita, Dai Koguchi, Morihiro Nishi, Shinji Kurosaka, Hideyasu Tsumura, Ken-ichi Tabata & Masatsugu Iwamura Department of Urology, Kitasato University School of Medicine, Sagamihara, Japan
Keywords Laparoscopic adrenalectomy; metastasis; survival Correspondence Takahiro Hirayama, Department of Urology, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan. Tel: +81 42 778 9091 Fax: +81 42 778 9374 Email: [email protected] Received: 3 July 2013; revised 22 September 2013; accepted 2 October 2013 DOI:10.1111/ases.12076
Abstract Introduction: Treating adrenal metastases from primary malignancies with laparoscopic adrenalectomy (LA) remains controversial. The aim of this study was to evaluate the feasibility, effectiveness and efficiency of LA for solitary adrenal metastasis. Methods: From November 2003 to September 2012, eight consecutive patients with adrenal metastasis were treated with LA. A retrospective study was conducted, and clinical and histological data were analyzed. Results: All LA were successfully performed. There were no major complications, blood transfusions or conversions to open adrenalectomy. The patients included seven men and one woman with a median age of 59 years at the time of operation. Adrenal metastases were most commonly noted to be from non-small-cell lung cancer (four patients) and renal cell carcinoma (four patients). The majority of adrenal metastases were unilateral (right: one patient; left: seven patients). One patient had bilateral metastases. The median overall survival was 14 months. Four patients (two with non-small-cell lung cancer; two with renal cell carcinoma) were alive with no evidence of metastatic disease as of October 2013. Conclusion: LA is a safe and effective procedure for patients with isolated metastases. Surgical resection with LA for a solitary adrenal metastasis from primary malignancy can achieve a good prognosis.
Introduction The development of minimally invasive surgical techniques has revolutionized many surgical procedures. Compared with traditional open surgery, the laparoscopic approach to major abdominal operations reduces organ system impairment, resulting in significantly less perioperative morbidity and recovery time (1). Since Gagner et al. reported their first laparoscopic adrenalectomy (LA) in 1992 (2), this minimally invasive approach has become the gold standard for removing benign lesions of the adrenal gland. However, applying LA for a solitary metastasis or primary adrenal carcinoma remains controversial because port-site metastasis or dissemination has been reported after LA for adrenal malignancies (3,4). Whereas primary adrenal carcinoma is a locoregionally aggressive disease, adrenal metastasis is often confined within the adrenal capsule, offering more
opportunities to obtain en bloc adrenalectomy. Therefore, some investigators recommend LA as an appropriate initial approach for a solitary adrenal metastasis (5,6). Thus, in the current study, we evaluate the feasibility, effectiveness and efficiency of LA for solitary adrenal metastases in eight consecutive patients.
Patients and Methods A retrospective single center study was conducted by analyzing the records of consecutive patients who underwent adrenalectomy for a solitary adrenal metastasis. From November 2003 to September 2012, nine adrenalectomies were performed in eight patients to treat adrenal metastasis at our institution (Kitasato University School of Medicine, Sagamihara, Japan). Bilateral diseases were counted as two adrenalectomies for one
Asian J Endosc Surg 7 (2014) 43–47 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
43
LA for adrenal metastasis
T Hirayama et al.
Table 1 Patient characteristics, and perioperative and postoperative data
Age Patient (years) Gender Side 1 2 3 4 5 6† 7 8 Median
56 59 48 61 57 59 77 71 59
M M M M F M M M
Lt. Lt. Lt. Lt. Rt. Bilateral Lt. Lt.
PM
Treatment for PM
NSCLC NSCLC NSCLC NSCLC Lt. RCC Lt. RCC Lt. RCC Rt. RCC
Surgery Chemotherapy Chemotherapy Surgery Surgery Surgery Surgery Surgery
Interval to diagnosis to AM Metastasi EBL Operative Hospital Survival (months) s size (mm) (mL) time (min) stay (days) (months) Status 24.0 31.0 25.0 11.0 70.0 73.0 52.0 61.0 41.5
82 30 50 70 50 75 30 86 60
20 40 NR NR 10 120 20 50 30
220.0 140.0 195.0 285.0 163.0 120.0 125.0 150.0 156.5
6.0 4.0 5.0 7.0 12.0 10.0 3.0 5.0 5.5
9 69 7 8 33 93 19 7 14
NEMD NEMD Dead due to PM Dead due to PM Dead due to PM Recurrence, but alive NEMD NEMD
†LA was performed for only one side and open surgery was performed for the other. AM, adrenal metastasis; EBL, estimated blood loss; F, female; LA, laparoscopic adrenalectomy; Lt., Left; M, male; NEMD, no evidence of metastatic disease; NR, not reported; NSCLC, non-small-cell lung cancer; PM, primary malignancy; RCC, renal cell carcinoma; Rt., Right.
patient. CT was used to diagnose solitary adrenal metastasis in all patients, and there was no evidence of extra-adrenal metastasis. Metastases discovered within 6 months of a previous treatment for primary malignancy were considered synchronous, and those discovered after 6 months were designated as metachronous. No percutaneous adrenal biopsy was performed for the diagnosis of malignancy. For all eight patients, LA was performed via a transperitoneal approach. Adrenal glands with surrounding fat were resected with the greatest of care to prevent tumor disruption. Specimens were extracted intact within a bag. After surgery, the patients were followed up every 3 months by physical examination and systemic CT. Survival was defined as the time between LA and death or last follow-up visit. The status (dead or alive) of each patient was obtained from hospital records.
Results Patients’ characteristics and perioperative and postoperative data are summarized in Table 1. The patients included seven men and one woman with a median age of 59 years (range, 48–77 years) at the time of operation. All LA were performed successfully. There were no major complications, blood transfusions or conversions to open adrenalectomy. All adrenal metastases were found without intensive adhesion to peri-adrenal structures and removed safely without capsular disruption. Renal cell carcinoma (RCC) was the most common primary malignancy (five adrenalectomies in four patients), followed by non-small-cell lung cancer (NSCLC) (four adrenalectomies in four patients). The majority of adrenal metastases were unilateral (right: one patient;
44
left: six patients); only one patient had bilateral metastases. Two patients received adrenalectomy on the same side as a previous nephrectomy. The patient with bilateral adrenal metastases from RCC underwent simultaneous procedures: (i) open adrenalectomy for adrenal metastasis on the same side as a previous open nephrectomy for RCC with a horseshoe kidney and (ii) LA for the other side of the adrenal metastasis (Figure 1a). Another patient who had undergone a previous laparoscopic nephrectomy underwent LA to remove the adrenal metastasis on the same side as the primary tumor (Figure 1b). All adrenal metastases were identified as metachronous metastasis over a median duration of 41.5 months after the detection of primary malignancies. Median tumor size was 60 mm (range, 30–86 mm), median operative time was 156.5 min (range, 120.0– 285.0), and median estimated blood loss was 30 mL (range, 10–120 mL). Median postoperative hospital stay was 5.5 days (range, 3.0–12.0 days). For two patients treated with substitution doses of glucocorticoids after surgery, hospital stay was more than 10.0 days. In all cases, pathological examinations revealed the diagnosis of metastasis related to primary malignancies. No local or port-site recurrence was observed during follow-up period. Median overall survival was 14 months (range, 7–93 months). Three patients, including two with metastases from NSCLC and one with metastasis from RCC, died from distant metastasis of other organs. Five patients were alive as of October 2013. Four patients, two with NSCLC and two with RCC, were alive with no evidence of metastatic disease. The longest survival (93 months) was observed in a male patient with primary malignancy of RCC with a horseshoe kidney. He had a pancreas metastasis 70 months after bilateral adrenalectomies and was treated with molecular-targeted therapy.
Asian J Endosc Surg 7 (2014) 43–47 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
LA for adrenal metastasis
T Hirayama et al.
Figure 1 Unenhanced CT images of the upper abdomen. (a) A 59-year-old male patient with bilateral adrenal metastases from RCC with a horseshoe kidney (arrows). Open adrenalectomy for adrenal metastasis on the same side as a previous open nephrectomy and LA for the other side of the adrenal metastasis were performed simultaneously. (b) A 77-year-old male patient with left adrenal metastasis from RCC (arrow). LA for adrenal metastasis on the same side as a previous laparoscopic nephrectomy was performed. LA, laparoscopic adrenalectomy; RCC, renal cell carcinoma
Discussion The adrenal gland is a frequent site of metastasis from various malignancies because of the gland’s rich sinusoidal blood flow and the multiple pathways of arterial blood supply (7). In Western countries, lung and breast cancers account for most adrenal metastases, followed by melanoma, hepatocarcinoma and renal cancer (8). Also, Lam and Lo reported that, in Hong Kong, lung cancer is the most common primary malignancy, followed by stomach and esophageal cancers (9). Ma et al. reported that the two most common sites of primary tumor were the kidney and lung, and these accounted for more than half of all cases of cancer in China (10). In the current study, adrenal metastases were most commonly noted to be from lung and kidney cancers (four of eight patients). According to autopsy-based reviews, adrenal metastases were found in 10%–27% of patients with malignancies, but isolated adrenal metastases were extremely rare (11,12). Lee et al. reported that only 4 of 1715 patients (0.2%) with extra-adrenal cancer had solitary adrenal metastasis at the first evaluation (12). As most adrenal metastases have smooth borders and do not invade neighboring organs, unenhanced CT is useful for detecting adrenal masses; it has a sensitivity of 72% and a specificity of 98% (13). Percutaneous biopsy also has a diagnostic value for adrenal metastasis. An ex vivo study with core biopsies of the adrenal gland showed a positive predictive value of 100% and a negative predictive value of 92% for the diagnosis of malignancy (14). However, complications associated with biopsy were also reported, with complication rates ranging from 3% to 13% (15). These complications include hematoma, pancreatitis, pneumothorax, retroperitoneal abscess and tumor recurrence along the needle track. Thus, in the current study, we did not perform
percutaneous biopsy in any patients in order to prevent tumor seeding. Surgical resection of adrenal metastases was first performed more than 30 years ago (16). Since then, many patients have benefited from surgical resection, and longtime survival can be achieved. Five-year or more survival after adrenalectomy has often been reported for various primary malignancies (Table 2) (17–25). In the current series, median survival after adrenalectomy was 14 months, and survival after 5 years was noted in two patients, one with RCC and one with NSCLC. Tumor type has been suggested to be a prognostic factor (10). Ma et al. reported that patients with RCC had the best survival rates, whereas patients with NSCLC had the worst survival rates (10). Zerrweck et al. showed that patients who presented with a nonrenal cancer had an increased mortality risk of almost fourfold compared to patients with RCC (26). In contrast, an acceptable survival rate was shown in a large series of patients with NSCLC treated at MD Anderson Cancer Center (Houston, USA) (25). Metachronous metastases also have a better survival rate, especially in patients with RCC (10). In the current study, all adrenal metastases were found to be metachronous. Synchronous lesions may be more aggressive and may grow faster than metachronous lesions. The difference in survival rates may be attributed to the intrinsic biological behavior of tumor types. Compared with open adrenalectomy, the benefits of LA are widely accepted with respect to analgesic use, return of functional status and perioperative outcome (1,27). LA has become the gold standard treatment for benign adrenal masses. However, LA for adrenal metastasis is still considered controversial, given that its technical challenges require advanced laparoscopic expertise. During our study, eight patients safely underwent LA for metastasis with a median size of 60 mm (range, 30–86 mm). No tumor disruption or major perioperative
Asian J Endosc Surg 7 (2014) 43–47 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
45
LA for adrenal metastasis
T Hirayama et al.
Table 2 Published series of adrenalectomies for metastatic disease from RCC or NSCLC Survival (months) Mean
Median
Long-term survivors (month)†
Selected series of adrenalectomies for adrenal metastases from NSCLC Lucchi et al. (17) 2005 10 80 Pfannshchmidt et al. (18) 2005 11 70 Strong et al. (19) 2007 29 127 Present study 2013 4 69
31 12.6 29 23
NR NR NR 8.5
10% 10% 22% 25%
Selected series of adrenalectomies for adrenal metastases from RCC Lau et al. (20) 2003 11 120 Siemer et al. (21) 2004 56 120 Antonelli et al. (22) 2006 48 142 Bahrami et al. (23) 2009 19 180 Present study 2013 4 93
48 20 99 NR 38
NR NR NR NR 26
20% 19.6% 24% 25% 25%
Author
Year
n
Maximum survival (months)
†More than 60 months. NR, not reported; NSCLC, non-small-cell lung cancer; RCC, renal cell carcinoma.
complication occurred, and four patients are still alive with no evidence of metastatic disease. Although the routine use for LA is usually limited to masses smaller than 60 mm (28), Nguyen et al. reported that large tumor size was not considered a contraindication for LA, even with metastases (29). Sancho et al. showed that metastasis size does not appear to have any influence on survival (15). However, all adrenal metastases should be removed under strict oncologic principals, including avoidance of tumor disruption and wide resection with an adequate margin (24,26). Although several investigators have reported that adrenal metastasis offers more opportunities to obtain en bloc adrenalectomy because it is often confined within the adrenal capsule, conversion to open adrenalectomy from laparoscopic surgery should not be delayed if an oncological resection cannot be performed (5,6). According to our current series, LA can be tackled successfully and safely by means of laparoscopy. Moreover, it is accepted that surgical resection with LA for a solitary adrenal metastasis from primary malignancy can achieve a good prognosis. It should be emphasized that there have been very few series of LA for metastases, and the limitations of retrospective studies are obvious. The small number of patients with isolated adrenal metastasis hinders performance of randomized and prospective studies, necessitating additional research and pooled analysis to confirm the validity of the current study. However, our study will be meaningful for those considering this surgical approach to remove adrenal metastases.
Acknowledgment The authors have no conflict of interest to report.
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