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- PATIENTS AND METHODS
- CONFLICT OF INTEREST
Current data suggest that adrenal-sparing approaches should be utilized when performing radical nephrectomy (RN) unless there are specific concerns for adrenal involvement indicated by high risk tumour characteristics (>7 cm [1–3], upper pole location [4–6]) or concerning radiographic findings [7–10]. The indications for ipsilateral adrenalectomy for small renal masses (T1a tumours) are even fewer, and the majority of adrenal glands in this scenario should be left in situ.
Although current literature demonstrates 10-year oncological equivalence when adrenal-sparing approaches are utilized [11,12], we have yet to clearly define the long-term consequences of an iatrogenic solitary adrenal gland on overall patient health. Although rendering a patient to a solitary adrenal does not appear to have a clinically relevant impact in the days immediately following surgery , it remains important to define the lasting consequences in these patients. We sought to evaluate the impact of ipsilateral adrenalectomy on overall survival (OS) through analysis of a large population-based cohort.
- Top of page
- PATIENTS AND METHODS
- CONFLICT OF INTEREST
Herein we report improved OS in patients undergoing adrenal-sparing RN as opposed to those undergoing concomitant adrenalectomy. The data suggest that adrenalectomy may adversely impact patients' overall health and wellbeing, resulting in long-term consequences. This is supported by the fact that adrenalectomy status was associated with OS but not CSS. These findings are further highlighted by our study design in which we limited our cohort to patients with T1a RCC who are almost universally candidates for adrenal-sparing approaches and for whom CSS is excellent.
Prior studies have demonstrated oncological equivalence for adrenal-sparing RN in appropriately selected patients based on either low risk tumour characteristics or radiographic findings [10,11]. Despite this, studies continue to report a slow adoption of adrenal-sparing approaches to RN . This may be due to the fact that few short-term consequences of ipsilateral adrenalectomy have been identified . Although it may be unnecessary from an oncological standpoint to remove the adrenal gland, the long-term health consequences on the patient are not well understood and require further investigation.
Potential exists for an increased risk of adrenal insufficiency and other serious long-term sequelae in patients with a solitary adrenal gland. Although individuals with adrenal insufficiency often present with non-specific symptoms (fatigue, anorexia, gastrointestinal discomfort), it can progress to more serious problems such as electrolyte imbalances, altered consciousness and refractory hypotension . Additionally, an intact adrenal-cortical response is essential to the body's ability to compensate in acute illness . Adrenal crisis can be life-threatening and occurs in as many as 42% of patients with adrenal insufficiency [19,20].
Although there are few reports of adrenal insufficiency directly attributable to unilateral adrenalectomy, other studies have demonstrated early alterations in cortisol response following unilateral adrenalectomy . Furthermore, we have a poor ability to preoperatively identify those who will suffer from clinically significant adrenal insufficiency following surgery . Patients undergoing RN with adrenalectomy are particularly prone to long-term adrenal-related treatment dilemmas because the contralateral gland remains at increased risk for developing metastasis, especially with higher risk tumours. In a recently published series, over 4000 nephrectomies were performed for RCC with a recurrence rate in the contralateral adrenal of 2.6% . This is consistent with previously reported autopsy studies identifying a 2.5% rate of contralateral adrenal metastasis . For these patients in whom an ipsilateral adrenalectomy has already been performed, definitive treatment would result in adrenal insufficiency. Moreover, the rate of adrenal insufficiency in patients with metastatic disease involving the adrenal gland has been reported to be in the range of 20% .
These patients are also susceptible to the consequences of non-malignant adrenal processes. The prevalence rates of incidental adrenal lesions range from 4% to 6% and increase significantly with age . Such developments in patients with a solitary adrenal gland further complicate the clinical scenario and decision-making process. The adrenal gland remains vulnerable to multiple causes of primary adrenal insufficiency. Although often bilateral, these causes of adrenal insufficiency can be seen unilaterally and may disproportionately impact patients with a solitary adrenal. The prevalence of primary adrenal insufficiency in western cultures is 50 in 1 000 000 and population studies identify significantly increased incidence in elderly patients . Additionally, patients with undiagnosed adrenal insufficiency may only manifest themselves during times of physiological stress. This knowledge provides a framework and mechanistic background for which to assess the long-term consequences of adrenalectomy on OS.
We must consider certain limitations when examining the results of our study. We acknowledge the retrospective nature of our database. We are limited in our ability to capture certain patient details (i.e. radiographic findings, comorbidities) and intraoperative events that may influence treatment decisions and eventual outcome. We attempted to address these concerns by limiting our cohort to a specific population (T1a tumours) that is ideal for evaluating our question of interest and also by controlling for confounding factors in the multivariable analysis. Additionally, we determined tumour characteristics and rates of adrenalectomy from pathology reports, as opposed to operative reports. If the adrenal gland was not mentioned, we assumed that it was not removed. While this also limits the potential accuracy of some of our clinical information, it is a conservative approach. Despite these limitations, our data provide us with long-term follow-up from a large, pathologically well characterized population-based cohort.
In summary, our findings demonstrate a modest yet significant association between ipsilateral adrenalectomy and OS. With longer follow-up, the adverse effects may be further amplified. Research is needed to elucidate the physiological impact, if indeed this relationship is causal. However, these findings further support the value of adrenal-sparing approaches at the time of RN.
Findings from our population-based analysis demonstrate worse OS in patients undergoing ipsilateral adrenalectomy with RN for RCC. We provide some of the only data demonstrating an association between adrenalectomy and long-term survival. Our results further emphasize the importance of adrenal-sparing approaches when performing RN, although further research is still needed to confirm these findings.