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Keywords:

  • adrenal glands;
  • adrenalectomy;
  • laparoscopy;
  • malignancy

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Objectives:  The treatment of malignant adrenal tumors using laparoscopic surgery remains controversial. We thus compared the perioperative outcome of the laparoscopic adrenalectomy for the treatment of malignant tumors with the outcome for benign tumors. We also evaluated the oncological outcome of the laparoscopic adrenalectomy for a malignancy.

Methods:  Since 1999 a total of nine laparoscopic adrenalectomies for a malignancy have been performed in nine patients. The median adrenal tumor size was 3 cm. The laparoscopic approach was transperitoneal in all cases. Seven patients had no evidence of a systemic metastatic disease, whereas two patients with a metastatic renal cell carcinoma had systemic metastatic disease at the time of the operation.

Results:  The median operation time was 165 min and the estimated blood loss was 75 mL in the laparoscopic adrenalectomy for a malignancy. There was no significant difference between laparoscopic adrenalectomy for malignant and benign tumors. Regarding the oncological outcome, seven of the nine patients, including the two palliative cases, treated with a laparoscopic adrenalectomy for a malignancy were alive at a median follow-up of 20 months. One patient died of other causes.

Conclusions:  Our results clearly indicate that a laparoscopic adrenalectomy for the treatment of a metastatic adrenal malignancy can be performed with an acceptable outcome as a minimally invasive method in carefully selected patients.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

A laparoscopic adrenalectomy has become the gold standard procedure for the treatment of benign adrenal tumors such as an aldosteronoma, Cushing's syndrome and/or subclinical Cushing's syndrome, and a pheochromocytoma. Malignant adrenal tumors are uncommon, however, and for most malignant tumors a surgical resection is the only opportunity for a cure. Regarding the operative procedure, the use of laparoscopic adrenalectomy for malignant tumors remains a matter of considerable controversy because the initial published case reports showed the possibility of the procedure generating a peritoneal carcinomatosis or a port site metastasis.1–7 However, several recent small series have described the use of laparoscopic adrenalectomy for a malignancy with acceptable oncological outcomes.8–15 We thus retrospectively analyzed the perioperative outcomes of a laparoscopic adrenalectomy for malignant tumors, and compared the findings with those for benign tumors at our single institution. We also evaluated the oncological outcomes of the laparoscopic adrenalectomy for a malignancy.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Since 1993, we have performed more than 150 laparoscopic adrenalectomies at our institution. Of these, nine patients with a pathologically confirmed adrenal malignancy were identified retrospectively. The laparoscopic approach was transperitoneal in all cases. The selection criteria for the laparoscopic approach were an adrenal mass of 10 cm or less without evidence of either a peri-adrenal infiltration or a caval thrombosis on the preoperative computed tomography (CT). A total 146 patients have undergone 148 laparoscopic adrenalectomies for benign tumors. These patients included 53 cases of primary aldosteronism, 49 cases of Cushing's syndrome, 23 cases of pheochromocytoma, 14 cases of a non-functioning adenoma and 7 cases of other disease. Three patients had bilateral adrenal tumors. Among them, two patients underwent a laparoscopic adrenalectomy twice, whereas a bilateral laparoscopic adrenalectomy was simultaneously performed in one patient. The laparoscopic approach was transperitoneal in 126 cases, retroperitoneal in 19 cases and 3 cases were not reported. The characteristics of the patients are shown in Tables 1 and 2.

Table 1.  The characteristics of patients who underwent a laparoscopic adrenalectomy for malignancy and their outcome
Pt. No.AgeSexSideTumor size (cm)Pathological diagnosisTreatment after adrenalectomyOutcomeFollow-up period (months)
  • These two patients with metastatic renal cell carcinoma had systemic metastatic disease at the time of operation. TKI, Tyrosine kinase inhibitor. DC, Dendritic cell.

178MLt4.5Adrenal CanoneAlive with disease (local recurrence)106
266MLt3.0Metastatic Ca (unorigined)noneDead of other causes20
364MRt2.0Renal cell Ca metastasis (clear cell type)noneAlive with disease (soft tissue metastasis)24
470MLt9.2Renal cell Ca metastasis (papillary type)TKI phase II trialAlive with disease25
568MRt3.0Renal cell Ca metastasis (clear cell type)DC therapyAlive with disease24
668MLt3.0Hepatocellular Ca metastasisnoneDead of disease10
772FRt2.4Renal cell Ca metastasis (clear cell type)noneAlive with disease (parathyroid metastasis)20
874MRt5.0Metastatic Ca (unorigined)noneNo disease evidence14
965MLt3.5Malignant melanomanoneAlive with disease (skin metastases)5
Table 2.  The characteristics of patients who underwent a laparoscopic adrenalectomy
 Benign tumorMalignant tumor
  • *

    P < 0.001 compared with the benign group.

  • **

    P < 0.001 compared with the benign group.

No. of patients1469
Median age (year)45.5 (16–79)68 (64–78)*
Male/Female46/1008/1**
Side(right/left/bilateral)66/77/34/5/0
Median tumor size (cm)3.0 (0.5–10.0)3.0 (2.0–9.2)

A laparoscopic adrenalectomy with transperitoneal approach was performed using a previously reported method.16 The laparoscopic retroperitoneal approach was performed by a modification of the method reported previously by Ono et al.17 Both procedures are usually performed with the patient in a flank position (60° or 90° for the transperitoneal approach and the full flank position for the retroperitoneoscopic approach). When a malignancy was suspected, we did not use the ultrasonic scissors in order to avoid the generation of a mist that might contain malignant cells.

Welch's t-test and the χ2 test were used for statistical comparisons. Significance was assumed for P-values of <0.05.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

A total 157 adrenalectomies were performed in 155 patients. Among them, nine patients had adrenal malignancy pathologically. These included the case of a primary adrenal carcinoma and eight cases of a metastatic adrenal carcinoma, including four with a metastatic renal cell carcinoma, two with a metastatic carcinoma of an unknown origin, one with a metastatic malignant melanoma and one with a metastatic hepatocellular carcinoma (Table 1). There were eight male patients and one female patient with a mean age of 68 years (range, 64–78 years). Regarding the tumor location, five were on the left side and four were on the right side. The median tumor size was 3.0 cm (range, 2.0–9.2 cm). (Tables 1, 2). Seven patients had no evidence of any systemic metastatic disease at the time of the operation. However, two patients with a metastatic renal cell carcinoma had systemic metastatic diseases at the time of the operation (Table 1). Patient no. 4 had a contralateral adrenal metastasis, and patient no. 5 had bilateral lung metastases. Both of them were resistant to a prior cytokine therapy and we decided to perform a dendritic cell (DC) therapy using their own tumor lysates.18 Since we had no frozen sections of their tumors, we performed laparoscopic adrenalectomy, with informed consent, to get the tumor tissues for the DC therapy.

We initially compared the perioperative data of the nine patients with the malignant tumors with those from the patients with the benign tumors. The patients' backgrounds for the benign adrenal tumors are also shown in Table 2. The median age of the malignant group was more than 20 years older than that of the benign group and a high incidence of male patients was observed in the malignant group. Unexpectedly, however, the median size of the malignant tumors was almost the same as that of the benign tumors (Table 2). There was only one case (patient No.1) that required a conversion to open surgery in the malignant group, because of tumor adhesion and uncontrollable bleeding, whereas three cases in the benign group required an open conversion (Table 3). Except for the converted case, the median operation time and the median estimated blood loss in the malignant group were 165 min (range, 103–303 min), and 75cc (range, 10–200 cc), respectively. These two results were comparable with those in the benign group without the conversion to open surgery (Table 3). The median number of days to the first oral feeding and the first ambulation in the malignant group were 1 day (range, 1–2 days) and 1 day (range, 1–2 days), respectively. The median duration of the postoperative hospital stay was 10.5 days (range, 7–14 days). Similarly, there was no statistical difference in these data between the two groups (Table 3). Regarding the perioperative complications of the laparoscopic adrenalectomy for malignancy, we experienced one case of a liver injury without a conversion to open surgery (Patient no. 3).

Table 3.  Perioperative data in patients who underwent a laparoscopic adrenalectomy
 Benign tumorMalignant tumor
  • Not specific in comparison to the benign group.

Operation time (min)180 (73–540)165 (103–303)
Estimated blood loss (cc)50 (4–1500)75 (10–200)
No. of allogenic transfusion20
No. of conversions to open surgery31
First oral feeding (days)1 (1–5)1 (1–2)
First ambulation (days)1 (1–3)1 (1–2)
Postoperative hospital stay (days)10 (2–26)10.5 (7–14)

Neither a peritoneal carcinomatosis nor a port site recurrence was observed in any of the patients with laparoscopic adrenalectomy for malignancy (Table 4). Seven patients without any systemic metastatic disease at the time of the operation did not receive any additional treatments after the adrenalectomy (Table 1). Among them, one patient (No. 8) is alive without any recurrence. One patient (No. 2) died of causes unrelated to cancer without any recurrence. A local recurrence was noted 74 months after the operation in patient no. 1 (Tables 1,4). A new distant metastasis was observed in four patients. In patient no. 6, a Th8–10 bone metastasis was detected one month after the operation, and he died of the disease 10 months postoperatively (Tables 1,4). In patient no. 9, several skin metastases were observed two months after the surgery, and they were surgically resected (Table 1). In patient no. 7, a parathyroid metastasis was identified six months after the operation and it was surgically resected (Table 1). Similarly, in patient no. 3, a soft tissue metastasis was found at his hip 20 months after the operation and it was surgically resected (Table 1). In two patients with systemic metastatic diseases at the time of the operation, neither a rapid growth of the other metastatic lesions nor the appearance of a new metastatic lesion was observed soon after the operation (data not shown). One patient (No. 4) changed his mind and entered a phase II trial of tyrosine-kinase inhibitor after recovering from the adrenalectomy (Table 1). The other patient (No. 5) received DC therapy after the operation (Table 1). In general, except for one patient who died of other causes, seven of eight patients who underwent a laparoscopic adrenalectomy for a malignancy were alive at a median follow-up of 20 months (Table 4).

Table 4.  Overall outcomes in patients who underwent laparoscopic adrenalectomy for malignancy
Pt outcomeNo. Pts (%)No. local recurrenceNo. other metastasisNo. carcinomatosis or port site recurrenceMedian follow-up (months)
  • Two patients with metastatic renal cell carcinoma had systemic metastatic disease at the time of operation.

No disease evidence1 (11%)   14
Alive with disease6 (67%)15 24
Dead of disease1 (11%) 1 10
Dead of other causes1 (11%)   20
Total916020

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

In the present study, we have evaluated the perioperative outcomes and the oncological outcomes following the use of a laparoscopic adrenalectomy for malignant tumors, because it remains a matter of considerable controversy. Regarding the perioperative outcomes, including the operation time, the estimated blood loss and the postoperative hospital stay, there was no statistical difference between laparoscopic adrenalectomy used for malignant tumors and that used for benign tumors (Table 3). These results indicate that a laparoscopic adrenalectomy for a malignancy can be safely performed with the use of appropriate selection criteria. In the selection criteria, although we consider that no evidence of a peri-adrenal infiltration on the preoperative CT is important, we experienced two cases that had severe adhesion in spite of no evidence of a peri-adrenal infiltration on the preoperative CT. One (patient no. 1) required an open conversion, and the other (patient no. 3) caused liver damage without conversion to open surgery. Thus, we always need to keep in mind the possibility of adhesion to the surrounding tissues when we perform a laparoscopic adrenalectomy for a malignancy. In this sense, when a malignancy is suspected, the laparoscopic adrenalectomy should be performed by expert laparoscopists, as Castillo et al. reported.19 In addition, the preoperative diagnosis is considered to be important, because the preoperative diagnosis in patient no. 1 was Cushing's syndrome based on the CT findings and hormonal examinations.

Regarding the oncological outcomes, neither a peritoneal carcinomatosis nor a port site metastasis was observed in any of the patients (Table 4), although the initial published case reports showed the possibility of both of them occurring.1–7 In this study, when a malignancy was suspected, we did not use the ultrasonic scissors in order to avoid the generation of a mist that might contain malignant cells, as Tsuru et al. reported.20 This modification of the surgical procedure may account for our result of no incidence of either a peritoneal carcinomatosis or a port site metastasis (Table 4). Except for a patient who died of causes unrelated to cancer without any recurrence, seven of the eight patients were still alive at a median follow-up of 20 months (Table 4). This result was beyond our expectation. Interestingly, all four patients with a metastatic renal cell carcinoma were alive, whereas the pathology in the only cancer-related death (patient no. 6, who had a Th8–10 bone metastasis one month after the operation) was a metastatic hepatocellular carcinoma. In this sense, the patient with an adrenal metastasis from a renal cell carcinoma may be a good candidate for a laparoscopic adrenalectomy. Similar findings were also reported by Heniford and Pratt.21 They reported that 62% of patients who underwent a curative adrenal resection with laparoscopy had no evidence of a renal cell carcinoma, with an average of 26 months of follow-up.21

The characteristic feature of our series is that we performed a laparoscopic adrenalectomy in two patients with an adrenal metastatic renal cell carcinoma who also had systemic metastatic diseases at the time of the operation. Both of them were resistant to prior cytokine therapy. Molecular targeting therapy has not yet been approved in Japan even now. The patients thus selected DC therapy using their own tumor lysates, which is a clinical trial in our institute.18 Since we had no frozen sections of the patients' tumors, we considered the way to get tumor tissues for the DC therapy. In this process, we considered that the operation should be minimally invasive, because it was not a radical, but a palliative operation. It is a well known fact that the stress of surgery induces an immunosuppression, sometimes resulting in the rapid growth of other metastatic sites.22 As a result, we selected and performed a laparoscopic adrenalectomy with informed consent. Neither the rapid growth of other metastatic lesions nor the appearance of a new metastatic lesion was observed in the two patients soon after the operation (data not shown), thus indicating that the laparoscopic adrenalectomy was really minimally invasive. In addition, the two patients are still alive with their disease at a median follow-up of 24.5 months (Table 1). Taken together, our results indicate that a laparoscopic adrenalectomy for an adrenal metastatic renal cell carcinoma can be performed with no problem even if the operation is palliative. However, such a palliative operation should be performed while carefully taking the subsequent DC therapy into consideration because the benefits of a palliative adrenalectomy alone in patients with metastatic renal cell carcinoma have yet to be confirmed.

The limitation of this study is that we experienced only one case of primary adrenal carcinoma where a local recurrence was noted 74 months after the operation. From the result, the role of laparoscopy in the management of primary adrenal malignancies may remain controversial. In this sense, a laparoscopic adrenalectomy can be safely performed with acceptable outcomes especially for the treatment of a metastatic adrenal malignancy.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

A laparoscopic adrenalectomy for a metastatic adrenal malignancy can be safely performed with acceptable outcomes as a minimally invasive method in carefully selected patients. In addition, our results also show the possibility that a laparoscopic adrenalectomy for an adrenal metastatic renal cell carcinoma can be performed without any problem even if the operation is palliative.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References