Routine Adrenalectomy Research Articles

Adrenalectomy During Radical Nephrectomy- Incidence and Oncologic Outcomes From the Canadian Kidney Cancer Information System (CKCis) -A Modern Era, Nationwide, Multicenter Cohort

ObjectiveTo characterize proportion of patients receiving adrenalectomy, adrenal involvement prevalence and oncologic outcomes of routine adrenalectomy in contemporary practice. Ipsilateral adrenalectomy was once standard during radical nephrectomy. However, benefit of routine adrenalectomy has been questioned because adrenal involvement of renal cell carcinoma (RCC) is low. MethodsAll patients receiving radical nephrectomy in the Canadian Kidney Cancer information system, a collaborative prospective cohort populated by 14 major Canadian centers, between January 2011 to February 2020 were included. Patients were excluded if they had non-RCC histology, multiple tumors, contralateral tumors, metastatic disease or previous history of RCC. Patient demographic, clinical, and surgical information were summarized and compared. Cox-proportional hazards was used for multivariable analysis. ResultsDuring study period, 2759 patients received radical nephrectomy, of these, 831(30.1%) had concomitant adrenalectomy. Pathological adrenal involvement was identified in 102 (3.7%overall; 12.3%of adrenalectomy). Median follow-up was 21.6months (Interquartile range 7.0-46.5). Patients with adrenalectomy had higher venous tumor thrombus (30.3% vs 9.6%; P <.0001), higher T stage (71.1% vs 43.4% pT3/4; P <.0001), lymph node metastases (17.6% vs 10.7%; P = .0035), Fuhrman grades (71.4% of Fuhrman grades 3/4 vs 56.2%; P <.0001) and increased proportion of clear cell histology (79.3% vs 74.5%; P = .0074) compared to the no adrenalectomy group. Adrenalectomy patients had higher risk of recurrence (HR 1.23; 95% CI 1.04-1.47; P = .019) and no difference in survival (HR 1.09, 95% CI 0.86-1.38, P = .48). ConclusionAdrenalectomy is not associated with better oncological outcome of recurrence/survival. Adrenalectomy should be reserved for patients with radiographic adrenal involvement and/or intra-operative adrenal involvement.

Routine adrenalectomy in renal cancer—an antiquated practice

For decades, complete removal of the kidney with all the contents of the Gerota's fascia (including the adrenal gland) has been a standard procedure for treating renal cell carcinoma (RCC). Two recent articles argue against routine adrenalectomy, and encourage adrenal preservation for the vast majority of patients with RCC.

Routine Adrenalectomy in Patients with Locally Advanced Renal Cell Cancer Does Not Offer Oncologic Benefit and Places a Significant Portion of Patients at Risk for an Asynchronous Metastasis in a Solitary Adrenal Gland

BackgroundThe indications for the removal of the ipsilateral adrenal gland in patients with renal cell carcinoma (RCC) and the long-term outcomes have not been well studied. ObjectiveWe evaluated the risk of synchronous and asynchronous adrenal involvement in patients with RCC and the effect of adrenalectomy on recurrence and survival in a large, single-institution cohort. Design, setting, and participantsFrom 1970 to 2006, 4018 consecutive patients with RCC treated by surgical extirpation (radical nephrectomy [RN]: 3107; partial nephrectomy [PN]: 911) from Mayo Clinic were studied for adrenal involvement. Risk of asynchronous adrenal metastasis and cancer-specific survival (CSS) were also compared between those who underwent concomitant ipsilateral adrenalectomy (n=1541) and those who did not (n=2477) using multivariate Cox models. InterventionSurgical removal of the adrenal gland at the time of kidney tumor resection. MeasurementsPrimary outcome is cancer specific survival; secondary outcomes are incidence of synchronous and asynchronous adrenal metastases. Results and limitationsMedian postoperative follow-up among those still alive was 8.2 yr (interquartile range [IQR]: 5.3–13.6). Synchronous ipsilateral adrenal involvement was rare (n=88; 2.2%). Ipsilateral adrenalectomy at the time of nephrectomy did not lower the risk of subsequent adrenal metastasis (hazard ratio [HR]: 0.96; 95% confidence interval [CI], 0.64–1.42) or improve CSS (HR: 1.08; 95% CI, 0.95–1.22). The development of asynchronous adrenal metastasis occurred in 147 patients (3.7%) at a median of 3.7 yr (IQR: 1.2–7.7) after initial surgery. The risk of developing an ipsilateral versus a contralateral asynchronous adrenal metastasis was equivalent at 10 yr in those who did not undergo adrenalectomy at initial surgery. This study is limited by its single-institution, nonrandomized nature. ConclusionsRoutine ipsilateral adrenalectomy in patients with high-risk features does not appear to offer any oncologic benefit while placing a significant portion of patients at risk for metastasis in a solitary adrenal gland. Therefore, adrenalectomy should only be performed with radiographic or intraoperative evidence of adrenal involvement.

Effect of routine ipsilateral adrenalectomy on cancer-specific survival and risk of adrenal insufficiency for patients with pT3/4 renal cell carcinoma.

324 Background: The indications for the removal of the ipsilateral adrenal gland in patients with renal cell cancer (RCC) have not been well defined. Most continue to advocate ipsilateral adrenalectomy in patients with risky features such as a tumor thrombus, large, locally advanced tumors, and/or upper pole tumors. We evaluated the oncologic outcomes of concurrent adrenalectomy with either partial (PN) or radical nephrectomy (RN) in a large single institution cohort. Methods: From 1970–2006, 4,019 consecutive patients with RCC treated by RN (n=3,107) or PN (n=912) from Mayo Clinic were studied for adrenal involvement. Risk of asynchronous adrenal metastasis and cancer specific survival (CS) were also compared between those who underwent concomitant adrenalectomy (n=1,464) and those who did not (n=2,555) using multivariate cox models. Results: Median postoperative follow-up was 6 years. Synchronous ipsilateral adrenal involvement was rare even for those with large (&gt;7cm) tumors (2.5%), upper pole (1.3%), and locally advanced (pT3/4) tumors (3.5%). The development of asynchronous adrenal metastasis occurred in 109 patients (2.7%) at a median of 3.7 years after initial surgery. The risk of developing an ipsilateral (1.4% 95% CI 0.8, 2.0) vs. contralateral (1.8% 95% CI 1.0, 2.6) asynchronous adrenal metastasis was equivalent at 10 years, in those who did not undergo adrenalectomy at initial surgery. At 10 years, 7.3% (99% CI: 4.4, 10.2) of patients with higher stage tumors (pT3/4) are predicted to develop a contralateral adrenal metastasis. On multivariate analysis, routine adrenalectomy was associated with a decreased risk of subsequent adrenal metastasis (HR 0.88: 99% CI 0.81, 0.95), but did not significantly impact CS (HR 1.15: 99% CI 0.99, 1.34). Conclusions: Asynchronous metastasis can usually be salvaged without apparent effect on CS. Ipsilateral adrenal involvement from RCC was uncommon even in large, locally advanced, and/or upper pole tumors. Routine adrenalectomy in these high risk patients may lead to an unacceptably high rate of adrenal insufficiency when a significant subset develops a contralateral adrenal metastasis. No significant financial relationships to disclose.

Routine Adrenalectomy Is Unnecessary During Surgery for Large and/or Upper Pole Renal Tumors When the Adrenal Gland Is Radiographically Normal

Concurrent adrenalectomy during renal surgery for renal cell carcinoma was once routine. More recent data suggest that adrenalectomy should be reserved for tumors 7 cm or greater, particularly those involving the upper pole. We evaluated the radiographic and pathological incidence of adrenal involvement in patients undergoing renal surgery for renal cell carcinoma 7 cm or greater. Patients who underwent renal surgery for tumors 7 cm or greater between 1999 and 2008 were identified from our kidney cancer registry. We used Fisher's exact test to determine whether radiographic tumor site predicted adrenal involvement. The Kaplan-Meier method and Cox proportional hazard regression models were used to analyze the impact of adrenal resection on outcome. Of 1,650 patients we identified 179 patients who underwent surgery for renal cell carcinoma 7 cm or greater. Of these patients 91 underwent concurrent total ipsilateral adrenalectomy at renal surgery with pathological adrenal involvement confirmed in 4 (4.4%). Upper pole site did not predict involvement (p = 0.83). Preoperative adrenal imaging was 100% sensitive and 92% specific to detect adrenal involvement by renal cell carcinoma with 100% negative predictive value. No survival advantage was noted on multivariate analysis when comparing patients who underwent adrenal resection to 88 in whom the adrenal gland was spared (p = 0.38). Synchronous ipsilateral adrenal involvement with renal cell carcinoma is rare even in cases of large and/or upper pole tumors, making routine adrenalectomy unnecessary. Preoperative adrenal imaging is highly sensitive and should inform the decision to perform adrenalectomy more than tumor size or site.

Management of the Adrenal Gland During Partial Nephrectomy

Nephron sparing surgery is an increasingly used alternative to Robson's radical nephroadrenalectomy. The indications for adrenalectomy in patients undergoing partial nephrectomy are not clearly defined and some surgeons perform it routinely for large and/or upper pole renal tumors. We analyzed initial management and oncological outcomes of adrenal glands after open partial nephrectomy. Institutional review board approval was obtained for this study. During partial nephrectomy the ipsilateral adrenal gland was resected if a suspicious adrenal nodule was noted on radiographic imaging, or if intraoperative findings indicated direct extension or metastasis. Concomitant adrenalectomy was performed in 48 of 2,065 partial nephrectomies (2.3%). Pathological analysis revealed direct invasion of the adrenal gland by renal cell carcinoma (1), renal cell carcinoma metastasis (2), other adrenal neoplasms (3) or benign tissue (42, 87%). During a median followup of 5.5 years only 15 patients underwent subsequent adrenalectomy (0.74%). Metachronous adrenalectomy was ipsilateral (10), contralateral (2) or bilateral (3), revealing metastatic renal cell carcinoma in 11 patients. Overall survival at 5 years in patients undergoing partial nephrectomy with or without adrenalectomy was 82% and 85%, respectively (p = 0.56). Adrenalectomy should not be routinely performed during partial nephrectomy, even for upper pole tumors. We propose concomitant adrenalectomy only if a suspicious adrenal lesion is identified radiographically or invasion of the adrenal gland is suspected intraoperatively. Using these criteria adrenalectomy was avoided in more than 97% of patients undergoing partial nephrectomy. Even using such strict criteria only 13% of these suspicious adrenal nodules contained cancer. The rarity of metachronous adrenal metastasis and the lack of an observable benefit to concomitant adrenalectomy support adrenal preservation during partial nephrectomy except as previously outlined.

The Therapeutic Value of Adrenalectomy in Case of Solitary Metastatic Spread Originating from Primary Renal Cell Cancer

Introduction: Solitary adrenal metastases occur in about 1.2–10% of renal cell cancer patients. Since the vast majority of intraadrenal lesions can be detected preoperatively, we and others have recently recommended to renounce a routine adrenalectomy during surgery of renal cell cancer. However, the impact of adrenalectomy on the patients’ clinical prognosis in case of a solitary metastatic lesion within the adrenal gland remains an issue of controversial discussion. Whereas some authors suggest adrenalectomy as a potentially curative treatment option in these cases, others compare its clinical value with that of a mere lymphadenectomy. Patients and method: Between 1981 and 2000, 648 patients (440 males and 208 females) underwent nephrectomy in combination with adrenalectomy in our clinic for the diagnosis of renal cell cancer. The median age at first diagnosis was 59 (range 33–84) and 60 (range 20–85) years for male and female patients, respectively. The median postoperative follow - up was 2.4 years (0.2–18 years). According to the TNM – classification system (2003) tumor stages were classified as follows: T1, 228 pat. (37%); T2, 70 pat. (11%); T3, 287 pat. (46%); T4, 37 pat. (6%). In total, 339 patients revealed regional lymph node or distant metastases at the time of the surgical treatment. Although metastases of the adrenal gland were diagnosed in 48 patients, solitary intraadrenal metastases without further systemic spread were observed in only 13 cases. Several patients’ and tumor characteristics (age, tumor stage and size, the presence of regional lymph node metastases, the presence of metastatic lesions at different organ sites as well as the detection of solitary intraadrenal metastases) were correlated with the patients’ overall survival by univariate and multivariate statistical analysis (logistic Cox regression analysis). Results: The median long – term survival was 4.8 years for the entire cohort of patients investigated. The median long – term survival was 13.8 years and 11.7 years for patients with no evidence of metastatic spread as well as for patients with a solitary intraadrenal metastatic lesion, respectively. Accordingly, the long – term survival rates at 5 and 10 years after surgery were 66%/50% and 51%/51% for patients with no evidence of metastatic spread or isolated intraadrenal metastases. This difference was not statistically significant. In contrast, for patients revealing lymph node or distant metastases at other organ sites, the median long – term survival was significantly decreased (lymph node metastases: 0.7 years; distant metastases: 1.2 years). Discussion: For patients with a solitary intraadrenal metastatic lesion, adrenalectomy is a potentially curative treatment option. The observation that the long – term survival of the latter patients is comparable to that of patients with organ – confined disease might suggest the establishment of a separate TNM – category for patients revealing a solitary metastasis within the adrenal gland and no hint at further systemic metastatic spread.

The need for routine adrenalectomy during surgical treatment for renal cell cancer: the Hannover experience.

To further clarify the need for routine adrenalectomy during the surgical treatment of renal cell cancer, as in the absence of clinically overt metastatic disease, tumorous lesions within the adrenal gland are found in only 2-10% of patients, with most being over-treated by adrenalectomy. The medical records of 819 patients undergoing adrenalectomy combined with nephrectomy, irrespective of the local extension of the primary tumour or the clinical stage at first diagnosis, were reviewed to determine the reliability of currently available imaging methods in predicting adrenal gland metastases. Several patient and tumour characteristics were correlated with the presence of intra-adrenal metastases, and their possible independent prognostic value was determined by a multivariate logistic regression model. There was metastatic spread into the adrenal gland in 27 of 819 (3.3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site were preoperative abdominal computed tomography scans interpreted as false-negative. On multivariate statistical analysis only the presence of distant metastases, vascular invasion within the primary tumour and multifocal growth of renal cell cancer within the tumour-bearing kidney were identified as independent predictors of the presence of intra-adrenal metastases. None of the patient or tumour characteristics evaluated reliably predicted the likelihood of adrenal metastases in patients with no evidence of disseminated metastatic spread. However, previously published data indicate that the frequency of metachronous metastases within the contralateral kidney (1.8-3.8%) is significantly higher than the risk of a preoperatively undetected isolated intra-adrenal metastatic lesion when currently available imaging modalities are applied. Therefore, routine adrenalectomy should not be recommended if the preoperative radiological examinations are normal.

The need for routine adrenalectomy during the surgical treatment of renal cell cancer - the Hannover experience

The need for routine adrenalectomy during the surgical treatment of renal cell cancer - the Hannover experience

Modulation by N-stearoylethanolamine of K+ and Mitotane Effects on Steroid Hormones Labeling in Human Adrenocortical Tissue

N-Acylethanolamine derivatives have attracted considerable attention of investigators owing to their effects on membrane processes. We studied the effect of stearoylethanolamine, NAE-18:0, upon the rate of [ 3 H]-cholesterol label incorporation into steroid hormones. We have evaluated the modulating effect of NAE-18:0 on corticosteroids labeling in the slices of conventionally normal tissue of human adrenals. The adrenal specimens were obtained from 3 patients undergoing routine adrenalectomy for unsuccessfully treated Cushing's disease or aldosteroma and androsteroma. The label incorporation varied widely in the three used samples of tissue. [ 3 H]-cholesterol label incorporation was increased when K + concentration in the incubation medium rose from 3.5 to 8.5 mM. NAE-18:0 further enhanced aldosterone labeling. Mitotane which is used for therapy of cortical carcinoma inhibited aldosterone labeling. NAE-18:0 attenuated the inhibitory effect of mitotane. NAE18:0 effect on corticosterone labeling was similar but less pronounced. The labeling of 17-hydroxy-hormones under the influence of NAE-18:0 changed to a lesser extent. The membranotropic mechanisms of NAE-18:0 and mitotane action are discussed.

IS ADRENALECTOMY A NECESSARY COMPONENT OF RADICAL NEPHRECTOMY? UCLA EXPERIENCE WITH 511 RADICAL NEPHRECTOMIES

We determine the incidence and characteristics of adrenal involvement in localized and advanced renal cell carcinoma, and evaluate the role of adrenalectomy as part of radical nephrectomy. The records of 511 patients undergoing radical nephrectomy with ipsilateral adrenalectomy for renal cell carcinoma at our medical center between 1986 and 1998 were reviewed. Mean patient age was 63.2 years (range 38 to 85), and 78% of the subjects were males and 22% were females. Patients were divided into subgroups of 164 with localized (stage T1-2 tumor, group 1) and 347 with advanced (stage T3-4N01M01, group 2) renal cell carcinoma. Staging of tumors was performed according to the 1997 TNM guidelines. A retrospective review of preoperative computerized tomography (CT) of the abdomen was performed. Radiographic findings were subsequently compared to postoperative histopathological findings to assess the predictive value of tumor characteristics and imaging in determining adrenal metastasis. Of the 511 patients 29 (5.7%) had adrenal involvement. Average size of the adrenal tumor was 3.86 cm. (standard deviation 1.89). Tumor stage correlated with probability of adrenal spread, with T4, T3 and T1-2 tumors accounting for 40%, 7.8% and 0.6% of cases, respectively. Upper pole intrarenal renal cell carcinoma most likely to spread was local extension to the adrenal glands, representing 58.6% of adrenal involvement. In contrast, multifocal, lower pole and mid region renal cell carcinoma tumors metastasized hematogenously, representing 32%, 7% and 4% of adrenal metastasis, respectively. The relationship between intrarenal tumor size (mean 8.9 cm., range 3 to 17) and adrenal involvement (independent of stage) was not statistically significant. Renal vein thrombus involvement was demonstrated in 8 of 12 cases (67%) with left and 2 of 9 (22%) with right adrenal involvement. Preoperative CT demonstrated 99.6% specificity, 99.4% negative predictive value, 89.6% sensitivity and 92.8% positive predictive value for adrenal involvement by renal cell carcinoma. With a low incidence of 0.6%, adrenal involvement is not likely in patients with localized, early stage renal cell carcinoma and adrenalectomy is unnecessary, particularly when CT is negative. In contrast, the 8.1% incidence of adrenal involvement with advanced renal cell carcinoma supports the need for adrenalectomy. Careful review of preoperative imaging is required to determine the need for adrenalectomy in patients at increased risk with high stage lesions, renal vein thrombus and upper pole or multifocal intrarenal tumors. With a negative predictive value of 99.4%, negative CT should decrease the need for adrenalectomy. In contrast, positive findings are less reliable given the relatively lower positive predictive value of this imaging modality. Although such positive findings may raise suspicion of adrenal involvement, they may not necessarily indicate adrenalectomy given the low incidence, unless renal cell carcinoma with risk factors, such as high stage, upper pole location, multifocality and renal vein thrombus, is present.

Real Indications for Adrenalectomy in Renal Cell Carcinoma

Objectives: Adrenalectomy is a part of radical nephrectomy because of the surgical oncology principle of a ‘wide margin beyond the malignancy’ and due to concern over possible metastases to the ipsilateral adrenal gland, especially in upper pole tumors. But, neither the frequency, predisposing factors of the renal cell carcinoma nor mechanisms of involvement of the adrenal gland are well defined. We assessed the ipsilateral adrenal involvement in renal cell carcinoma to determine whether ipsilateral adrenalectomy during radical nephrectomy is essential. Material and Method: In a series of 15,347 autopsies in Jena from 1985 through 1996, 272 renal cell carcinoma with 24 adrenal metastases were found. In the same period 9 adrenal metastases were found in 639 radical nephrectomies. Contralateral and bilateral metastases were seen in 15 cases of the autopsy series and in 2 cases of the operative series. Results: The risk of adrenal metastases correlated with multifocal tumors, pleomorphic cell type, anaplastic growth pattern and tumors that were larger than 2.5 cm. Of the 24 renal cell carcinomas with adrenal metastases in the autopsy series, 23 had evidence of widespread disease and 22 had lymph node metastases. A preoperative abdominal computerized tomography was performed in all 9 patients of the operative series with renal cell carcinoma and adrenal involvement. The adrenal gland was considered abnormal in 8 of the 9 cases (88.9%). Only in 1 patient was the computerized tomography incorrectly interpreted as negative. Conclusion: We think adrenalectomy should only be performed if there is radiographic evidence of metastases in the adrenal gland or adrenal infiltration by a large upper-pole tumor is possible. Macroscopically normal adrenal glands should not be removed during tumor nephrectomy because the need and benefit of routine adrenalectomy are extremely limited.

On the Necessity of Adrenal Extirpation Combined with Radical Nephrectomy

Adrenal metastasis of renal cell carcinoma usually is an autopsy finding and seldom a clinical diagnosis. The incidence of ipsilateral suprarenal gland involvement also can be identified by histological examination of the organ with radical nephrectomy.The necessity of adrenalectomy performed in combination with nephrectomy is discussed. After a retrospective examination of our patients we discovered 8 adrenal metastases among 138 radical nephrectomies. Five patients who also had metastases in the lymph nodes (stages pN1 to pN2) died after an average of 26.4 months. Three patients without lymph node involvement are free of tumor. In these cases routine adrenalectomy must be regarded as a possible curative treatment. (J. Urol., 144: 842–844, 1990)