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The American Journal of Surgery”
Nationwide analysis of adrenocortical carcinoma reveals higher perioperative morbidity in functional tumors
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Punam P. Parikh*, Gustavo A. Rubio, Josefina C. Farra, John I. Lew
Division of Endocrine Surgery, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States
ARTICLE INFO
Article history: Received 11 July 2017 Received in revised form 9 August 2017 Accepted 21 August 2017
Keywords:
Adrenocortical carcinoma Functional tumor Clinical outcomes
ABSTRACT
Background: Current adrenalectomy outcomes for functional adrenocortical carcinoma (ACC) remain unclear. This study examines nationwide in-hospital post-adrenalectomy outcomes for ACC.
Methods: A retrospective analysis of the Nationwide Inpatient Sample database (2006-2011) to identify unilateral adrenalectomy patients for functional or nonfunctional ACC was performed. Patient de- mographics, comorbidities and postoperative outcomes were evaluated by t-test, Chi-square and multivariate regression.
Results: Of 2199 patients who underwent adrenalectomy, 87% had nonfunctional and 13% had functional ACC (86% hypercortisolism, 16% hyperaldosteronism, 4% hyperandrogenism). Functional ACC patients had significantly more comorbidities, and experienced certain postoperative complications more frequently including wound issues, adrenocortical insufficiency and acute kidney injury with longer hospital stay compared to nonfunctional ACC (P < 0.01). On multivariate analysis, functional ACC was an independent prognosticator for wound complications (28.1, 95%CI 4.59-176.6).
Conclusion: Patients with functional ACC manifest significant comorbidities with certain in-hospital complications. Such high-risk patients require appropriate preoperative medical optimization prior to adrenalectomy.
@ 2017 Elsevier Inc. All rights reserved.
1. Introduction
Adrenocortical carcinoma (ACC) is a rare and aggressive endo- crine tumor of the adrenal gland with a reported annual incidence of approximately 1-2 cases per million individuals per year.1,2 The clinical presentation may be characterized by functional symptoms related to adrenal hormone overproduction, including hyper- cortisolism, hyperaldosteronism and hyperandrogenism and/or by local symptoms due to compression by the tumor mass. Approxi- mately 40% of ACC do not secrete hormones and therefore, may present as large nonfunctional tumors causing local mass effect.3 As a result, most patients present with advanced disease, and have a median survival time of <12 months.3
Complete surgical excision with curative intent remains the
mainstay of treatment for this aggressive endocrine malignancy.4 While surgical resection offers the best chance to achieve long- term survival, ACC is still associated with a 5-year survival ranging from 16% to 45%, largely due to disease recurrence.2,3 Surgical evaluation for primary ACC should determine the appro- priate extent of resection for each patient amenable to surgical treatment. Depending upon variables such as functional status and hormone secretion profile, tumor size, location and patient anat- omy, optimal surgical treatment may vary from radical adrenalec- tomy to complex en bloc multi-organ resection.2,5
Unfortunately, disease rarity has restricted the assessment of large numbers of patients with ACC. Given the scarcity of studies with robust patient sample size, perioperative outcomes after adrenalectomy for functional ACC remain unclear. This study is one of the first in the literature to examine nationwide in-hospital outcomes after adrenalectomy for ACC. Based on surgeon experi- ence and current literature, the authors hypothesize that functional ACC may be associated with worse perioperative outcomes as compared to nonfunctional ACC.
* Corresponding author. Division of Endocrine Surgery, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, 1120 NW 14th St, 4th Floor, Clinical Research Building 410P, Miami, FL 33136, United States.
E-mail address: Pparikh@med.miami.edu (P.P. Parikh).
2. Methods
A retrospective cross-sectional analysis using data from the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (HCUP-NIS) from 2006 to 2011 was performed. This large sample size allows for analysis of rare conditions such as ACC stratified by tumor functionality. Clinical and pathologic data of 2199 consecutive patients with ACC who underwent adrenalec- tomy were analyzed. Patients were initially identified by a primary procedure involving unilateral adrenalectomy using International Classification of Diseases, Ninth Revision (ICD-9) codes 07.21, 07.22 and 07.29. Patients with a primary diagnosis of ACC (ICD-9194.0) were included and stratified based on diagnosis of functional (hormonally active) compared to nonfunctional ACC. The functional ACC group included patients with Cushing’s syndrome (ICD- 9255.0), Conn’s syndrome (ICD-9255.12) or primary hyper- aldosteronism (ICD-9255.10) and hyperandrogenism (ICD-9255.2). All remaining patients were classified as having nonfunctional ACC.
Patients with metastases to the adrenal gland from secondary malignancies (ICD-9198.7) were excluded. Patients with a diagnosis of pheochromocytoma (ICD-9255.6) were also excluded given that these patients represent a separate diagnostic entity from ACC. All operative cases listing nephrectomy as the primary procedure performed were excluded (ICD-9 55.4/55.54/55.52). Lastly, lapa- roscopy was found only in a limited subset of nonfunctional pa- tients and therefore, excluded given lack of a comparative group in patients with a functional adrenal tumor.
Patient characteristics including demographic, socioeconomic and comorbidities were recorded and compared between the aforementioned cohorts. Variables available from HCUP-NIS included age, sex, race, payer type, admission status (elective versus non-elective) and hospital characteristics such as urban versus rural location, and teaching versus non-teaching hospital. Hospital annual adrenalectomy volume was also calculated using unique NIS hospital identifiers assigned to each case. Hospitals were then stratified into quartiles by annual adrenalectomy vol- ume. Comorbidities including history of diabetes mellitus type 2, hypertension, congestive heart failure, chronic lung disease, kidney failure, liver disease, obesity, coagulopathy and peripheral artery disease were also recorded. A modified version of the Charlson Comorbidity Index was calculated for each patient and compared between groups.º
Dependent postoperative variables included in-hospital com- plications and length of stay. Perioperative complications were identified using ICD-9 diagnostic codes largely based on a previ- ously published model with exception of in-hospital death that is reported in HCUP-NIS.7 Perioperative complications analyzed included intraoperative vascular, spleen or liver injury, blood transfusion and hematoma formation. Wound complications analyzed included surgical site infections, seroma, dehiscence, and delayed healing. Endocrine complications included adrenocortical insufficiency. Medical complications included pulmonary embo- lism, renal, cardiovascular and pulmonary adverse events. All complications listed refer to in-hospital events, as there is no post- discharge data in the HCUP-NIS database.
Of note, on multivariate analysis, each row represents a multi- variable logistic regression model with biochemical functional status as the main predictor variable. Models also include: age (years), gender (woman, man), race (Asian, Black, Hispanic, White, others), insurance (Medicare, Medicaid, private, uninsured/other), medical comorbidities (congestive heart failure, chronic lung dis- ease, coagulopathy, hypertension, obesity, liver disease, renal fail- ure, peripheral vascular disease, diabetes mellitus), admission status (elective, emergent/urgent), hospital location/teaching sta- tus, and hospital annual adrenalectomy volume quartile.
Statistical analyses were performed using SPSS Statistical Pack- age version 22 (IBM, Chicago, IL). Categorical data were analyzed using Chi-squared tests, and Student t-tests were used for normally distributed continuous variables. Risk-adjusted multivariate logis- tic regression models for each of the primary outcomes included the primary predictor group (functional ACC versus nonfunctional ACC), in addition to co-variables including demographic charac- teristics, insurance status, comorbidities and admission status. Adjusted odds ratios (OR) with corresponding 95% confidence in- tervals (95% CI) along with P values and area under the curve (AUC) for each model were calculated. A P < 0.05 was considered statis- tically significant for all analyses. This study of de-identified patient data was exempt from review by the Institutional Review Board (IRB) at the University of Miami Leonard M. Miller School of Medicine.
3. Results
Of 2199 consecutive patients with ACC who underwent unilat- eral adrenalectomy, 13% (n = 276) had functional ACC compared to 87% (1923) of patients with nonfunctional ACC (Table 1). Among patients with functional ACC, 86% had hypercortisolism and 16% (n = 44) had hyperaldosteronism. Hyperandrogenism was found in 4% (n = 10) of all functional ACC patients. On average, patients with functional ACC were younger (51 vs. 55 years, respectively; P < 0.01) and more likely to be women (63% vs. 54%, respectively; P < 0.01) than those patients with nonfunctional ACC. There were no statistically significant differences in terms of race and insurance type between groups. All patients included in this study underwent open resection for ACC. Adrenalectomies were performed during emergent hospital admission 24% and 16% of the time in functional and nonfunctional ACC groups, respectively (P < 0.01). Further- more, the majority of patients in each group underwent adrenal- ectomy at an urban hospital (100% vs. 95%, respectively; P < 0.01) and teaching institution (85% vs. 77%, respectively; P < 0.01). Pa- tients with functional ACC were more likely to undergo adrenal- ectomy at hospitals in the highest quartile for adrenalectomy volume (37% vs. 29%, respectively; P < 0.01) (Table 1).
Overall, functional ACC patients had a significantly higher rate of several preoperative comorbidities including diabetes mellitus type 2 (33% vs. 19%, respectively; P < 0.01), hypertension (81% vs. 58%, respectively; P < 0.01), congestive heart failure (11% vs. 4%, respectively; P < 0.01), obesity (31% vs. 11%, respectively; p < 0.01), and coagulopathy (9% vs. 3%, respectively; P < 0.01) compared to nonfunctional ACC. The functional ACC group was also more likely to be associated with a Charlson comorbidity index of ≥2 as compared to the nonfunctional group (21% vs. 17%, respectively; P < 0.01) (Table 2).
Overall, perioperative complication rates were higher in pa- tients with functional ACC compared to patients with nonfunc- tional ACC, but did not reach significance (46% vs. 41%, respectively; P = 0.16). While rate of in-hospital death was similar between both cohorts (2% vs. 2%, respectively; P = 0.77), certain perioperative adrenalectomy complications were more prevalent in the func- tional ACC group of patients. Functional ACC patients were signif- icantly more likely to incur a postoperative wound complication (5% vs. 1%, respectively; P < 0.01), adrenocortical insufficiency (10% vs. 5%, respectively; P < 0.01) and acute kidney injury (14% vs. 6%, respectively; P < 0.01) compared to nonfunctional ACC patients. Patients with functional ACC had higher rates of postoperative hematoma (9% vs. 6%, respectively; P = 0.054) and pulmonary embolism (3% vs. 2%, respectively; P = 0.11), although this differ- ence was not statistically significant. Intraoperative complications including vascular and liver injury were infrequent, and did not differ between groups. Conversely, splenic injury was more
| Characteristics | Overall (n = 2199) | Functional (n = 276, 13%) | Nonfunctional (n = 1,923, 87%) | P Value |
|---|---|---|---|---|
| Mean age (SD) | 55 (15) | 51 (15) | 55 (15) | <0.01 |
| Sex | <0.01 | |||
| Women | 55% | 63% | 54% | |
| Men | 45% | 46% | 37% | |
| Race | 0.29 | |||
| White | 77% | 73% | 78% | |
| Black | 9% | 9% | 9% | |
| Hispanic | 8% | 11% | 8% | |
| Asian | 3% | 4% | 3% | |
| Native American | 0.3% | 0% | 0.3% | |
| Other | 3% | 3% | 3% | |
| Payer type | 0.09 | |||
| Medicare | 27% | 22% | 28% | |
| Medicaid | 9% | 12% | 8% | |
| Private | 58% | 59% | 58% | |
| Uninsured/other | 6% | 7% | 6% | |
| Hospital Location/Teaching Status | <0.01 | |||
| Rural | 5% | 0% | 5% | |
| Urban, Non-teaching | 18% | 15% | 18% | |
| Urban, Teaching | 78% | 85% | 77% | |
| Admission Status | <0.01 | |||
| Elective | 83% | 76% | 84% | |
| Emergent | 17% | 24% | 16% | |
| Hospital Annual Adrenalectomy Volume (Quartile) | <0.01 | |||
| 1st (<4/year) | 22% | 12% | 23% | |
| 2nd (≤4-10/year) | 21% | 23% | 21% | |
| 3rd (≤10-26/year) | 27% | 28% | 27% | |
| 4th (>26/year) | 30% | 37% | 29% |
SD, standard deviation.
ACC, adrenocortical carcinoma.
commonly seen in nonfunctional ACC patients as compared to their counterparts (10% vs. 4%, respectively; P < 0.01). Mean hospital stay was 9 and 7 days for functional and nonfunctional ACC groups, respectively (P < 0.01) (Table 3).
On risk-adjusted multivariate logistic regression, functional ACC was an independent prognosticator for wound complications (OR 28.1, 95% CI 4.59-176.6, P < 0.01) and lower rate of blood trans- fusion (OR 0.68, 95% CI 0.47-0.97, P < 0.033) (Table 4). On risk- adjusted multivariate analysis for overall postoperative complica- tions, certain factors such as Asian race (OR 1.91, 95% CI 1.06-3.46, P = 0.03), Black race (OR 2.72, 95% CI 1.89-3.90, P < 0.01), elective admission status (OR 0.61, 95% CI 0.70-0.80, P < 0.01), and Charlson comorbidity index of 1 (OR 1.61, 95% CI 1.27-2.05, P < 0.01) and ≥2 (OR 1.78 95% CI 1.35-2.36, P < 0.01) were independently associated with perioperative complications (Table 5).
4. Discussion
ACC is an aggressive endocrine malignancy typically resistant to chemotherapy and radiation where surgical resection is the only potentially curative treatment.3 Overwhelmingly nonfunctional, ACC are either discovered incidentally on abdominal imaging or as tumor enlargement leading to compressive symptoms. The remaining subset of functional ACC may be associated with autonomous cortisol, aldosterone or androgen hypersecretion. However, perioperative outcomes following adrenalectomy for functional ACC have not been well defined due to inherent limita- tions of studying such a rare disease. This contemporary population-based analysis of the HCUP-NIS database examines in- hospital outcomes after unilateral adrenalectomy in patients with functional and nonfunctional ACC. To the authors’ knowledge, this study represents one of the largest series in the literature to review patient perioperative outcomes related to functional and
| Characteristics | Overall (n = 2199) | Functional (n = 276, 13%) | Nonfunctional (n = 1,923, 87%) | P Value |
|---|---|---|---|---|
| Comorbidities | ||||
| Diabetes Mellitus | 21% | 33% | 19% | <0.01 |
| Hypertension | 61% | 81% | 58% | <0.01 |
| Congestive Heart Failure | 5% | 11% | 4% | <0.01 |
| Chronic Lung Disease | 15% | 12% | 15% | 0.30 |
| Renal Failure | 6% | 5% | 6% | 0.61 |
| Liver Disease | 4% | 5% | 4% | 0.23 |
| Obesity | 13% | 31% | 11% | <0.01 |
| Coagulopathy | 4% | 9% | 3% | <0.01 |
| Peripheral Artery Disease | 4% | 6% | 4% | 0.24 |
| Charlson Comorbidity Index | ||||
| 0 | 57% | 51% | 58% | <0.01 |
| 1 | 26% | 28% | 26% | |
| ≥2 | 17% | 21% | 17% |
ACC, adrenocortical carcinoma.
| Characteristics | Overall (n = 2199) | Functional (n = 276, 13%) | Nonfunctional (n = 1,923, 87%) | P Value |
|---|---|---|---|---|
| Overall Complications | 42% | 46% | 41% | 0.16 |
| In-Hospital Death | 2% | 2% | 2% | 0.77 |
| Intraoperative Complications | 18% | 14% | 19% | 0.09 |
| Vascular Injury | 10% | 11% | 10% | 0.58 |
| Spleen Injury | 9% | 4% | 10% | <0.01 |
| Liver Injury | 0.5% | 0% | 0.5% | 0.23 |
| Wound Complication | 2% | 5% | 1% | <0.01 |
| Infection | 1.3% | 5.1% | 0.8% | <0.01 |
| Seroma | 0.0% | 0.0% | 0.0% | 0.99 |
| Delayed healing | 0.0% | 0.0% | 0.0% | 0.99 |
| Dehiscence | 0.5% | 0.0% | 0.6% | 0.21 |
| Requiring wound drainage | 0.7% | 0.8% | 0.0% | 0.14 |
| Blood Transfusion | 21% | 25% | 20% | 0.08 |
| Hematoma | 6% | 9% | 6% | 0.054 |
| Adrenocortical Insufficiency | 6% | 10% | 5% | <0.01 |
| Pulmonary Embolism | 2% | 3% | 2% | 0.11 |
| Acute Kidney Injury | 7% | 14% | 6% | <0.01 |
| Cardiac Complications | 2% | 0% | 2% | 0.02 |
| Pulmonary Complications | 19% | 17% | 19% | 0.44 |
| Length of Stay, Days Mean (SD) | 7 (8.0) | 9 (9) | 7.0 (8) | <0.01 |
ACC, adrenocortical carcinoma.
nonfunctional ACC.
Functional adrenal tumors hypersecrete hormones that increase risk for metabolic and cardiovascular disease, making early diag- nosis and subsequent adrenalectomy paramount for successful outcomes.8 In accordance with previous reports, glucocorticoids and/or aldosterone have been known as the most frequent hor- mones oversecreted, and women are most frequently affected.5,9 This sex difference could be the consequence of the role of estro- gen in adrenal tumorigenesis, where suggested mechanisms include the enhancement of adrenocortical cell proliferation mediated by 17ß-estradiol.10 In this study, patients with hyper- cortisolism represented the majority among functional ACC. Pa- tients with functional ACC also had significant preoperative comorbidities. Specifically, functional ACC patients had higher rates of diabetes, hypertension, congestive heart failure, obesity and coagulopathy compared to patients with nonfunctional ACC. Furthermore, functional ACC patients had significantly more post- operative complications including wound issues, acute kidney injury and adrenocortical insufficiency, which may be supported by both the higher Charlson comorbidity index and proclivity for emergent operation, as compared to their nonfunctional counter- parts. Lastly, the higher rate of certain postoperative complications may in part explain the longer length of hospitalization in
| Outcomes | Functional adrenocortical carcinoma vs. nonfunctional ACC | ||
|---|---|---|---|
| aOR (95% CI) | P value | AUC | |
| Any complication | 0.99 (0.74-1.32) | 0.95 | 0.65 |
| In-hospital death | 1.76 (0.65-4.79) | 0.27 | 0.85 |
| Intraoperative technical complication | 0.69 (0.46-1.01) | 0.06 | 0.60 |
| Wound complication | 28.1 (4.59-176.6) | <0.01 | 0.98 |
| Pulmonary complication | 1.03 (0.71-1.49) | 0.89 | 0.75 |
| Cardiac complication | e | 0.99 | 0.87 |
| Pulmonary embolism | 0.74 (0.18-3.04) | 0.68 | 0.87 |
| Blood transfusion | 0.68 (0.47-0.97) | 0.033 | 0.69 |
| Adrenocortical insufficiency | 1.46 (0.84-2.55) | 0.18 | 0.78 |
ACC, adrenocortical carcinoma.
aOR (95%CI), adjusted odds ratio with 95% confidence interval.
AUC, area under the curve.
functional compared to nonfunctional ACC patients.
A majority of patients in this study underwent adrenalectomy at urban teaching hospitals. However, patients with functional ACC underwent adrenalectomy at highest volume hospitals more frequently, and this may reflect referral patterns for these more complicated cases. Previous studies have shown improved adre- nalectomy outcomes at higher volume centers.11,12 However, one study found that treatment at high volume centers did not improve long-term survival for patients with ACC.13 In our study, while patients with functional ACC were more likely to undergo opera- tion at highest volume hospital centers, they were more likely to encounter worse outcomes including a subsequent higher rate of specific perioperative complications as compared to their nonfunctional counterparts.
While the rate of in-hospital mortality is similar between groups in this study, patients who experienced early mortality, as defined by death within two years, had significantly higher rates of cortisol- secreting tumors, nodal metastasis, synchronous distant metastasis and R1 or R2 resections in a multicenter review of actual 10-year survivors after ACC resection.3 Among 180 patients enrolled in the aforementioned study, only 12 patients (7%) were actual 10- year survivors where most patients (67%) had non-secreting tu- mors.3 None of the 10-year survivors had hypercortisolism, a
| Any complication | OR (95% CI) | P value |
|---|---|---|
| Age | 1.01 (0.996-1.014) | 0.31 |
| Women (vs Men) | 0.85 (0.70-1.04) | 0.12 |
| Race (vs White) | ||
| Black | 2.72 (1.89-3.90) | <0.01 |
| Hispanic | 0.95 (0.65-1.40) | 0.81 |
| Asian | 1.91 (1.06-3.46) | 0.03 |
| Payer Type (vs Medicare) | ||
| Medicaid | 0.95 (0.63-0.1.44) | 0.81 |
| Private insurance | 0.86 (0.65-1.14) | 0.30 |
| Hyperfunctional ACC (vs Nonfunctional) | 0.99 (0.74-1.32) | 0.95 |
| Elective Admission (vs Emergent) | 0.61 (0.70-0.80) | <0.01 |
| Charlson Comorbidity Index (vs 0) | ||
| 1 | 1.61 (1.27-2.05) | <0.01 |
| ≥2 | 1.78 (1.35-2.36) | <0.01 |
ACC, adrenocortical carcinoma.
finding attributed to the negative effects of cortisol production on tumor cell growth and cell immunity.5
In another study of 202 patients with adrenal tumors, 148 pa- tients had a secreting tumor, of which 95 patients (64%) had mixed hormone secretion, 41 patients (28%) had hypercortisolism, 10 patients (7%) had hyperandrogenism and 2 patients (1%) had hyperaldosteronism.5 On univariate analysis, poor survival was associated with hypersecreting adrenal tumors (HR 1.63, P = 0.04), especially for glucocorticoid secreting tumors (alone or associated with other steroids) (HR 2.33, P < 0.001) and mineralocorticoid secreting tumors (HR 1.96, P = 0.01).5 Conversely, patients having an adrenal incidentaloma had higher survival rates (HR 0.32, P = 0.004).5 In another report of 72 patients with ACC, cortisol oversecretion was also found to be a negative prognosticator for survival.9,14,15 Poor prognosis of cortisol-secreting tumors may be related to its associated co-morbidities. It is also possible that the immunosuppressive effects of excess cortisol favor tumor growth and metastasis.5 Alternatively, the pathophysiology of cortisol oversecreting ACC may lead to the growth of a more aggressive tumor.5
In the authors’ current study, functional status was shown on multivariate analysis to be one of the most important variables in determining the risk of postoperative wound complications. In another study, functional status of ACC was found to be the most important variable in determining the risk of metastasis or local recurrence.16 They observed that adrenal tumors secreting cortisol only or with mixed secretion had an odds ratio of 45.17 for the occurrence of metastasis or relapse.16 Interestingly, the association of hyperandrogenism was protective and resulted in a better prognosis among both children and adults alike.16 These findings have been corroborated by another study of 32 ACC patients where individuals with isolated hyperandrogenism had the lowest rate of disease progression and death compared with cortisol-secreting (P < 0.01) and even nonfunctioning ACC patients (P < 0.05).1
While many studies in the literature validate the association of functional tumor status with poor patient outcome after adrenal- ectomy for ACC, particularly when in association with Cushing’s syndrome,1,3,5 the effect of hypercortisolism on disease recurrence may differ from that of primary disease. In a multi-institutional study, several important determinants of poor survival after cura- tive intent resection of recurrent ACC, including distant metastases, multifocal disease and disease-free interval of less than 12 months were identified.17 Interestingly, hormonal hypersecretion did not have a significant prognostic impact on survival in patients un- dergoing repeat resection, and therefore, did not preclude long- term survival after surgery in this setting.17
Traditionally, open surgical resection has been the procedure of choice in the management of ACC. This finding is expected, as pa- tients with functional and nonfunctional adrenal tumors generally undergo adrenalectomy for tumors with known or suspected ma- lignancy.18,19 However, in recent years, an increasing number of reports have investigated the use of open resection for all cases of ACC with a number of authors advocating the use of laparoscopic adrenalectomy in this setting.20-22 In the authors’ study, a low percentage of patients underwent laparoscopic resection, all of who had nonfunctioning ACC (9% overall), and therefore, were excluded given the inability to compare to functional ACC patients, who were all documented as undergoing open adrenalectomy. This discrepancy may be due, in part, to potentially larger tumor size or more advanced disease severity in functional compared to nonfunctional ACC necessitating an open approach. Nonetheless, the most important component of the surgical approach to ACC is to ensure adequate resection margins, which may be achieved by both laparoscopic and open surgical approaches depending on patient and tumor characteristics.
There are certain additional limitations of this study. HCUP-NIS is an administrative database that relies on diagnostic and proce- dural codes. There is an inherent risk of coding errors leading to missed or inaccurate diagnoses. This can result in over or under- estimation of complication rates analyzed in this study. For example, subclinical disease is not reported in this database, potentially contributing to a higher number of nonfunctional versus functional adrenal tumors as compared to that in the current literature. In addition, certain parameters of interest, such as TNM staging, tumor size, R0 resection, intraoperative blood loss, intra- operative hemodynamic instability and operative time are not re- ported in HCUP-NIS and therefore, could not be analyzed. More importantly, since there is no post-discharge data, the current analysis is limited to in-hospital events. Therefore, complications occurring after hospital discharge and readmissions were not captured in this data set. Lastly, the authors were unable to analyze the proportion of laparoscopic cases between groups likely due to limitations in coding where only a small subset of patients with a nonfunctional adrenal tumor were found to have undergone lapa- roscopy, and therefore excluded from this study. Nevertheless, this large nationwide study provides an overview of perioperative complication rates for adrenalectomy in the setting of this rare malignancy that can be used to facilitate prognostication of patients with ACC.
5. Conclusion
ACC is a rare and aggressive adrenal tumor where complete surgical excision with curative intent remains the mainstay of treatment. Among functional ACC patients undergoing adrenalec- tomy, patients with hypercortisolism represent the majority. Pa- tients with functional ACC present with significant preoperative comorbidities. These patients also experience higher rates of certain postoperative complications such as wound issues, adre- nocortical insufficiency and acute kidney injury, ultimately leading to longer length of hospitalization. Patients with functional ACC should undergo appropriate preoperative medical optimization and counseling in preparation for adrenalectomy.
Disclosure
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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