Impact of Laparoscopic Adrenalectomy on Overall Survival in Patients with Nonmetastatic Adrenocortical Carcinoma
Kelly T Huynh, MD, David Y Lee, MD, Briana J Lau, MD, Devin C Flaherty, DO, PhD, JiHey Lee, PhD, Melanie Goldfarb, MD, FACS
BACKGROUND: Appropriate use of laparoscopic adrenalectomy (LA) for adrenocortical carcinoma (ACC) re- mains controversial because complete resection with negative margins is the best chance for potential cure. This study compared the oncologic outcomes and overall survival (OS) of LA and open adrenalectomy (OA) for ACC.
STUDY DESIGN: A retrospective analysis of the National Cancer Data Base (NCDB) between 2010 and 2014 identified 423 European Network for the Study of Adrenal Tumors (ENSAT) stage I to III ACC patients who had LA (n = 137) or OA (n = 286). Outcomes and OS were compared between the 2 groups.
RESULTS: Patients who underwent OA had more advanced stage disease (p = 0.0001), larger (≥5 cm) tumors (p < 0.0001), and were younger (age less than 55 years, p = 0.05). Nodal assessment was rare in LA (n = 4) compared with OA (n = 88) (p < 0.0001). Margin positivity was affected only by surgical approach in patients with T3 tumors (LA 54.6% vs OA 21.7%; p = 0.0009). Neither surgical procedure nor any socio-demographic factor(s) affected OS for the entire cohort. Only positive margins (p = 0.007), positive nodes (p = 0.02), tumor extension (p = 0.01), and more advanced ENSAT stage (p = 0.004) increased mortality. When stratified by disease stage, LA decreased OS for patients with stage II disease (p = 0.04), and remained an independent risk factor for death on multivariate analysis (hazard ratio [HR] 1.86, 95% CI 1.02 to 3.38; p = 0.04). Only positive margins decreased OS in the entire cohort (HR 2.17, 95% CI 1.32 to 3.57; p = 0.002).
CONCLUSIONS: Use of LA may decrease OS in select patients with ACC. Because margin status remains the strongest predictor of mortality, caution should be used in selecting LA for patients with ACC. (J Am Coll Surg 2016;1:1-8. @ 2016 by the American College of Surgeons. Pub- lished by Elsevier Inc. All rights reserved.)
CME questions for this article available at http://jacscme.facs.org
Disclosure Information: Authors have nothing to disclose. Timothy J Eberlein, Editor-in-Chief, has nothing to disclose.
Abstract presented at the Pacific Coast Surgical Association’s 87th Annual Meeting, Kohala Coast, HI, February 2016.
Received March 21, 2016; Revised May 6, 2016; Accepted May 15, 2016. From the Departments of Surgical Oncology (Huynh, D Lee, Lau, Flaherty, Goldfarb), Biostatistics (J Lee), John Wayne Cancer Institute at Providence St John’s Health Center, Santa Monica, CA.
Correspondence address: Melanie Goldfarb, MD, FACS, John Wayne Can- cer Institute at Providence St John’s Health Center, 2200 Santa Monica Blvd, Santa Monica, CA 90404. email: melaniegoldfarbmd@gmail.com; goldfarbm@jwci.org
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that portends a poor prognosis secondary to its late stage at presentation and high recurrence rates.1-5 Estimated 5-year survival is 82% for stage I dis- ease, but drops dramatically for patients with advanced disease to 50% for stage III patients and only 13% for those with stage IV disease.6 Often patients are diag- nosed with large primary tumors that may invade adja- cent tissues or organs, or demonstrate vascular involvement.2,7 As such, complete operative resection with negative margins remains the only potential cure for patients with ACC.4,8-11 In cases in which local inva- sion is already present, curative resection remains feasible, but overall survival (OS) in these patients is much lower. 12,13
| Abbreviations and Acronyms | |
| ACC | = adrenocortical carcinoma |
| ENSAT | = European Network for Staging of Adrenal Tumors |
| HR | = hazard ratio |
| LA | = laparoscopic adrenalectomy |
| LND | = lymph node dissection |
| NCDB | = National Cancer Data Base |
| OA | = open adrenalectomy |
| OS | = overall survival |
Laparoscopic adrenalectomy (LA) was initially described in 1992 and has become the gold standard for treatment of benign adrenal tumors.14-17 In multiple retrospective studies, LA is associated with lower opera- tive complication rates, shorter hospital stays, reduced 30-day morbidity, and lower overall costs.18-22 However, the role of LA for treatment of patients with ACC re- mains controversial, particularly as it relates to its onco- logic outcomes. Several studies cite an increased risk of tumor capsule violation, tumor fragmentation, port site or peritoneal carcinomatosis, as well as a reduced ability to achieve an R0 resection as reasons to avoid utilizing a laparoscopic approach.2,3,23-26 However, other series have shown comparable results between the laparoscopic and open approaches, although the optimal tumor size and stage of patients selected for LA is still highly debat- able.7,27-31
Given the rarity of ACC, most of the studies regarding laparoscopic vs open adrenalectomy have been single institution studies and are limited by small numbers.2,3,7,23,24,27,29-31 In addition, many of the studies included only early stage patients or those with more favorable tumor characteristics such as smaller size and lack of tumor extension into adjacent fat or other nearby organs.29-31 Given the conflicting data, it is impossible to make generalized conclusions as to the appropriateness of laparoscopic resection for malignant adrenal tumors. Therefore, this study compared the oncologic outcomes and OS of LA and OA in patients diagnosed with Euro- pean Network for the Study of Adrenal Tumors (ENSAT) stage I to III ACC (nonmetastatic) in the National Cancer Data Base (NCDB) between 2010 and 2014.
METHODS
Patient population and data collection
The NCDB is a joint project of the American Cancer Society and the American College of Surgeons. It is a nationwide clinical oncology database of more than
1,500 Commission on Cancer (CoC)-accredited facil- ities, and it captures an estimated 70% of newly diag- nosed cancers in the United States annually.32 This study was determined by the Institutional Review Board to be exempt from oversight because of the de-identified nature of the data.
| Characteristic | OA group (n = 286) | LA group (n = 137) | p Value |
|---|---|---|---|
| Age, y, mean ± SD | 53.3 ± 18.5 | 58.6 ± 15.0 | 0.002* |
| Age, y, n (%) | |||
| <55 | 138 (48.3) | 52 (38.0) | 0.05* |
| ≥55 | 148 (51.8) | 85 (62.0) | |
| Sex, n (%) | |||
| Female | 170 (59.4) | 89 (65.0) | 0.28 |
| Male | 116 (40.6) | 48 (35.0) | |
| Facility type, n (%) | |||
| Academic | 168 (58.7) | 74 (54.0) | 0.06 |
| Community | 106 (37.1) | 62 (45.3) | |
| Other | 12 (4.2) | 1 (0.7) | |
| Facility location, n (%) | |||
| West | 27 (9.4) | 13 (9.5) | 0.03* |
| Midwest | 68 (23.8) | 29 (21.2) | |
| South | 108 (37.8) | 43 (31.4) | |
| Northeast | 50 (17.5) | 42 (30.7) | |
| Unknown | 33 (11.5) | 10 (7.3) | |
| Race, n (%) | |||
| Asian/Pacific Islander | 8 (2.8) | 2 (1.5) | 0.88 |
| White non-Hispanic | 233 (81.5) | 113 (82.5) | |
| Black non-Hispanic | 19 (6.6) | 9 (6.6) | |
| Hispanic | 13 (4.6) | 8 (5.8) | |
| Other | 13 (4.6) | 5 (3.7) | |
| Insurance, n (%) | |||
| Private | 153 (53.5) | 65 (47.5) | 0.13 |
| Public/government | 103 (36.0) | 61 (44.5) | |
| Uninsured | 19 (6.6) | 10 (7.3) | |
| Unknown | 11 (3.9) | 1 (0.7) | |
| Income, n (%) | |||
| Comfortable | 84 (29.4) | 52 (38.0) | 0.30 |
| Moderate | 158 (55.2) | 64 (46.7) | |
| Low | 43 (15.0) | 20 (14.6) | |
| Unknown | 1 (0.4) | 1 (0.7) | |
| Education, n (%) | |||
| High | 55 (19.2) | 16 (11.7) | 0.17 |
| Moderate | 73 (25.5) | 32 (23.4) | |
| Low | 157 (54.9) | 88 (64.2) | |
| Unknown | 1 (0.4) | 1 (0.7) |
*Significant.
LA, laparoscopic adrenalectomy; OA, open adrenalectomy.
Using the NCDB (between 2010 and 2014), patients with ACC were identified on the basis of the International Classification of Diseases for Oncology, 3rd edition (ICD- O-3) for site C74.0-C74.9 and histology 8370.3 (adre- nal cortical carcinoma). Only patients with primary ACC were included. The time frame was chosen based on recording of the surgical approach, which was started in 2010. Based on codes for tumor size (T1, ≤ 5 cm confined to adrenal; T2, >5 cm confined to adrenal; T3, any size with extension into adjacent fat), tumor extension, nodal status, and presence or absence of metastasis, the ENSAT stage was determined. Stage I patients included those with tumors ≤ 5 cm with no extra-adrenal extension;
stage II were patients with tumors > 5 cm but still without extra-adrenal extension; and stage III patients included those with tumors of any size with either inva- sion of adjacent organs or with regional lymph node metastasis, but no distant disease.6 Patients were placed in a “no lymph nodes positive” group if lymph nodes were not examined. Patients with metastatic disease (M1) (ENSAT stage IV) or with unknown surgical approach were excluded.
The LA group included patients who underwent laparoscopic and robotic assisted adrenalectomy. Laparoscopic and robotic operations that were converted to open were included in the OA group.
| Characteristic | OA group (n = 286) | LA group (n = 137) | p Value |
|---|---|---|---|
| Tumor size, cm, mean ± SD | 12.7 ± 7.1 | 8.0 ± 5.8 | <0.001* |
| ENSAT I | 3.3 ± 1.1 | 3.6 ± 1.1 | 0.50 |
| ENSAT II | 13.1 ± 7.6 | 7.9 ± 2.3 | <0.0001* |
| ENSAT III | 13.3 ± 5.9 | 10.6 ± 10.6 | 0.09 |
| Tumor size, cm, n (%) | |||
| <5 | 19 (6.6) | 27 (19.7) | <0.0001* |
| ≥5 | 267 (93.4) | 110 (80.3) | |
| Lymph nodes examined, n (%)* | |||
| Yes | 88 (30.8) | 4 (2.9) | <0.0001* |
| No | 198 (69.2) | 133 (97.1) | |
| Lymph nodes positive, n (%) | |||
| Yes | 17 (5.9) | 0 | 0.004* |
| No+ | 269 (94.1) | 137 (100) | |
| N0, n | 71 | 4 | |
| NX, n | 198 | 133 | |
| Lymphovascular invasion, n (%) | |||
| Yes | 133 (46.5) | 50 (36.5) | 0.13 |
| No | 95 (33.2) | 57 (41.6) | |
| Unknown | 58 (20.3) | 30 (21.9) | |
| Margin status | 0.58 | ||
| Positive | 43 (15.0) | 25 (18.3) | |
| Negative | 218 (76.2) | 98 (71.5) | |
| Unknown | 25 (8.7) | 14 (10.2) | |
| Primary tumor extension, n (%) | |||
| None (T1 or T2) | 165 (57.7) | 95 (69.3) | 0.003* |
| Adjacent fat (T3) | 77 (26.9) | 36 (26.3) | |
| Adjacent organ (T4) | 44 (15.4) | 6 (4.4) | |
| ENSAT stage, n (%) | |||
| I | 11 (3.9) | 20 (14.6) | 0.0001* |
| II | 152 (53.2) | 75 (54.7) | |
| III | 123 (43.0) | 42 (30.7) |
*Significant.
“One patient in each group with unknown status of lymph nodes examined was included in the “No” group.
*This group included patients with negative lymph nodes (NO) and those who did not have lymph nodes examined (NX). ENSAT, European Network for the Study of Adrenal Tumors; LA, laparoscopic adrenalectomy; OA, open adrenalectomy.
Statistical analysis
Univariable comparison of socio-demographic variables, clinico-pathologic factors, and adjuvant therapies between the LA and OA groups were performed using chi-square test, or Student’s t-test, as appropriate. Factors found to be significant in a univariable analysis were then entered into a multivariable analysis using multivariate logistic regression. Because complete opera- tive resection has been shown to affect outcomes for ACC patients, all variables were assessed for impact on margin status, both in the entire cohort and after stratification by T stage, with the same statistical methods.
Three-year OS was compared using Kaplan-Meier and the log-rank test both for the entire cohort and after strat- ification by ENSAT stage. Multivariable Cox propor- tional hazard regression analyses incorporated variables with p value < 0.1 on the log-rank test. The final models were built using a stepwise selection method. All statistical analyses were performed on SAS version 9.3 (SAS Insti- tute), and p values ≤ 0.05 were considered significant.
RESULTS
Patient socio-demographic characteristics
There were 423 patients with ENSAT stage I to III ACC who met inclusion criteria for the study. A total of 137 patients (32.4%) had an LA and 286 patients (67.6%) had an OA. With the exception of patients in the LA group being older than those in the OA group (mean age ± SD: LA, 58.6 ± 15.0 years; OA, 53.3 ± 18.5 years; p = 0.002) and more frequently from the Northeast (30.7% vs 17.5%), no other socio- demographic characteristic differed between the 2 groups (Table 1).
Tumor characteristics and treatment
Patients who had an OA had larger tumors (mean size, 12.7 ±7.1 cm vs 8.0±5.8cm,p <0.001) and presented with more advanced disease (ENSAT stage III) (OA 43.0% vs LA 30.7%; p = 0.0001) (Table 2). Addition- ally, more patients in the OA group had T4 tumors defined by ENSAT staging that extended into an adjacent organ (OA 15.4% vs LA 4.4%; p = 0.003). However, margin positivity and the presence of lymphovascular in- vasion did not differ significantly between the 2 groups. Nodal assessment was performed in only 4 patients (2.9%) in the LA group, whereas 88 patients (30.8%) in the OA had lymph nodes examined (p < 0.0001); 5.9% of all patients in the OA group had positive lymph nodes compared with no patients who underwent LA (p = 0.004). Lastly, margin status was not affected by surgical approach. However, after stratification by T stage,
| Characteristic | OA group (n = 286) | LA group (n = 137) | p Value | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Radiation | |||||
| Yes | 57 | 19.9 | 23 | 16.8 | 0.57 |
| No | 222 | 77.6 | 112 | 81.8 | |
| Unknown | 7 | 2.5 | 2 | 1.5 | |
| Chemotherapy | |||||
| Yes | 104 | 36.4 | 35 | 25.6 | 0.03* |
| No | 182 | 63.6 | 102 | 74.5 | |
| Hormone therapy | |||||
| Yes | 7 | 2.5 | 2 | 1.5 | 0.67 |
| No | 275 | 96.2 | 134 | 97.8 | |
| Unknown | 4 | 1.4 | 1 | 0.7 | |
*Significant.
LA, laparoscopic adrenalectomy; OA, open adrenalectomy.
patients with T3 tumors who underwent LA had greater rates of margin positivity than patients who had an OA (LA 54.6% vs OA 21.7%; p = 0.0009).
Adjuvant radiation (<20%) and hormonal therapy (<3%) were given in a minority of patients in both the OA and LA groups (Table 3). However, adjuvant chemo- therapy was administered in more than one-third of the OA patients vs only a quarter of those undergoing laparo- scopic resection (p = 0.03).
Survival analyses
Median follow-up for patients in the LA group was 21.9 months and 22.0 months in the OA group. For the entire cohort, only positive margins (p = 0.007), positive nodes (p = 0.02), tumor extension (p = 0.01), and more advanced ENSAT stage (p = 0.004) increased mortality in univariate analyses (Table 4). After multivariate anal- ysis, only positive margins decreased 3-year OS in the entire cohort (hazard ratio [HR] 2.17, 95% CI 1.32 to 3.57; p = 0.002). However, when stratified by disease stage, LA decreased 3-year OS for patients with stage II disease (Fig. 1) and remained an independent risk factor for death on multivariate analysis (HR 1.86, 95% CI 1.02 to 3.38; p = 0.04). For patients with ENSAT stage III tumors, those who were female (HR 0.51, 95% CI 0.29 to 0.90, p = 0.02) or received adjuvant chemo- therapy (HR 0.44, 95% CI 0.24 to 0.80, p = 0.007) had improved 3-year OS.
DISCUSSION
Complete surgical resection remains the mainstay of treat- ment for patients with ACC and offers the only potential
| Variable | Overall survival, % | p Value |
|---|---|---|
| Age, y | ||
| <55 | 60.9 | 0.42 |
| ≥55 | 49.2 | |
| Sex | ||
| Female | 58.5 | 0.22 |
| Male | 48.8 | |
| Facility type | 0.24 | |
| Academic | 48.3 | |
| Community | 54.4 | |
| Other | 87.5 | |
| Facility location | ||
| West | 52.2 | 0.37 |
| Midwest | 67.7 | |
| South | 46.2 | |
| Northeast | 57.0 | |
| Unknown | 65.8 | |
| Race | ||
| Asian/Pacific Islander | 100 | 0.57 |
| White non-Hispanic | 55.8 | |
| Black non-Hispanic | 57.1 | |
| Hispanic | 48.9 | |
| Other | 54.6 | |
| Insurance | ||
| Private | 56.3 | 0.73 |
| Public/government | 52.9 | |
| Uninsured | 69.2 | |
| Unknown | 58.3 | |
| Income | ||
| Comfortable | 56.5 | 0.26 |
| Moderate | 53.0 | |
| Low | 58.2 | |
| Education | ||
| High | 52.8 | 0.26 |
| Moderate | 61.8 | |
| Low | 51.9 | |
| Tumor size, cm | ||
| <5 | 62.5 | 0.68 |
| ≥5 | 53.9 | |
| Lymph nodes examined | ||
| Yes | 52.2 | 0.52 |
| No | 55.4 | |
| Lymph nodes positive | ||
| Yes | 28.6 | 0.02* |
| No+ | 56.1 | |
| N0 | 57.9 | |
| NX | 55.3 |
(Continued)
| Variable | Overall survival, % | p Value |
|---|---|---|
| Lymphovascular invasion | ||
| Yes | 54.2 | 0.08 |
| No | 60.2 | |
| Unknown | 50.2 | |
| Margin status | ||
| Positive | 42.8 | 0.007* |
| Negative | 58.5 | |
| Unknown | 49.8 | |
| Primary tumor extension | ||
| None (T1 or T2) | 60.0 | 0.01* |
| Adjacent fat (T3) | 44.4 | |
| Adjacent organ (T4) | 56.0 | |
| ENSAT | ||
| I | 80 | 0.004* |
| II | 58.4 | |
| III | 46.7 | |
| Radiation | ||
| Yes | 58.2 | 0.96 |
| No | 53.8 | |
| Unknown | 40.0 | |
| Chemotherapy | ||
| Yes | 59.3 | 0.64 |
| No | 51.6 | |
| Hormonal therapy | ||
| Yes | 88.9 | 0.25 |
| No | 52.8 | |
| Unknown | 66.7 |
*Significant.
“This group included patients with negative lymph nodes (NO) and those who did not have lymph nodes examined (NX).
One patient in each group with unknown status of lymph nodes examined was included in the “No” group.
ENSAT, European Network for the Study of Adrenal Tumors.
for cure. Because the risk of recurrence after surgery can be as high as 50% to 70%, and adjuvant therapy has been largely ineffective, the choice of surgical approach must be highly scrutinized so that patients have the best chance for improved survival.33-35 Although LA has been well established for treatment of patients with benign adrenal tumors and affords advantages well established with mini- mally invasive surgery, including decreased perioperative morbidity and lower costs, its role for ACC remains highly scrutinized.14-22 In this study, positive margins decreased OS for all patients, patients with T3 tumors had higher rates of margin positivity, and patients who had LA for stage II disease had a decreased OS compared with patients who had an OA. By the ENSAT staging system, stage III patients are defined as those having T3 or T4 tumors.
1.0
Proportion of Patients Alive
0.8
p=0.34
0.6
0.4
0.2
0.0
0
10
20
30
40
Time, Months
A
Group
LA
OA
1.0
Proportion of Patients Alive
0.8
0.6
p=0.04
0.4
0.2
0.0
0
10
20
30
Time, Months
40
B
Group
LA
OA
1.0
Proportion of Patients Alive
0.8
0.6
0.4
p=0.88
0.2
0.0
0
10
20
30
40
Time, Months
C
Group
LA
OA
The inclusion of more patients with T4 tumors in the OA group likely accounts for the reason why OS was not worse in the LA group for stage III patients.
In a recent meta-analysis by Autorino and colleagues,36 which included a series of 9 retrospective case-controlled studies published in a contemporary era (2010 to 2014), as in this study, the authors’ findings were similar. They reported that tumors treated with LA were signifi- cantly smaller (p < 0.001), and a higher proportion had earlier stage disease (stage I to II: 80.8% in LA groups vs 67.7% in OA groups, p < 0.001).36 Although they did not find a difference in time to recurrence or cancer- specific mortality, LA was associated with a higher risk of peritoneal carcinomatosis at the time of recurrence (relative risk [RR] 2.39; 95% CI 1.41 to 4.04; p = 0.001).36 Because complete surgical resection offers the best chance for cure, which would not be feasible with peritoneal carcinomatosis, they concluded that OA should still be considered the standard for surgical man- agement of ACC and that the laparoscopic approach should be offered in “carefully selected” ACC patients. Another recent multi-institutional analysis reported that margin status was an independent predictor of decreased OS in patients with nonmetastatic disease.37 Margonis and associates37 showed that both recurrence-free survival (p = 0.03) and OS (p < 0.001) were lower in patients with an R0 vs R1 (defined as margin > 1 mm) resection. Because positive margins was the only predictor of decreased OS, in ACC, in which tumors can be infiltrative on pathology but not apparently infiltrative on gross visu- alization during surgery, LA may be viewed a suboptimal procedure that jeopardizes the patient’s best chance for long-term survival. Opponents of LA for ACC also cite other oncologic concerns including increased risk for tumor spillage and recurrences at port sites or in the peritoneum. 2,3,23-26,33,38
It is unknown whether the difference in OS between LA and OA for stage II patients observed in this study could be a function of stage migration, ie, if lymph nodes were not examined, then some stage II patients might really be unknown stage III patients. This is a possibility because only 2.9% of patients who had LA had any nodes examined; however, only 30.8% of patients under- going OA had their nodes examined, so both groups were subject to potential under-staging. Many surgeons do not routinely perform a formal lymph node dissection (LND) because it is controversial, and the number of nodes involved is not part of the staging system. The largest study from the German ACC group looked at 283 patients and found that there was a reduced risk of tumor recurrence and disease-related death in patients undergoing LND vs no LND.39 However, despite im- provements in staging, there is conflicting evidence with regard to improved disease-free survival or recurrence. 39,40
In this analysis, stage III patients appeared to benefit from adjuvant chemotherapy despite historically disap- pointing treatment results in general.2 This may reflect advances in single and multiagent chemotherapy that have so far not been reported in such a large group due to the rarity of the malignancy.
This study represents the largest comparison to date of LA vs OA for nonmetastatic ACC. However, the study has inherent limitations. In addition to coding errors or missing data, the foremost limitation is the lack of information on disease recurrence and disease- specific survival. Additionally, it is unknown if there was a suspicion for cancer before the operation leading to selection bias. Lastly, because the NCDB only cap- tures data on the type of surgical approach for ACC starting in 2010, the follow-up time is limited. Howev- er, most deaths from ACC are likely to occur within the first 5 years and would have been captured by our data.
Given the rarity of this malignancy, it is unlikely that a prospective randomized controlled trial will be per- formed, and this underscores the need for a multi- institutional prospective database and standardized treat- ment protocols. Conversely, even in more common malignancies, such as rectal cancer, which has been stud- ied in previous and ongoing randomized controlled tri- als, the debate regarding the oncologic safety of laparoscopic vs open surgery remains unresolved.41-43 Most studies have been designed as noninferiority trials comparing laparoscopic vs open surgery, and although similar safety and completeness of resection have been shown, the long-term data on survival outcomes remains to be seen. Additionally, these studies excluded rectal cancers invading adjacent tissues or organs, citing that laparoscopic resection of large tumors is difficult and can lead to a less than complete surgical resection, and therefore, a higher rate of locoregional recurrence. 42,43 Although not looked at specifically in our study, surgeon experience with laparoscopic surgery also plays an important role in cancer operation outcomes and is even more challenging when dealing with rare malig- nancies such as ACC.
CONCLUSIONS
Although there may be a selection bias for smaller tumors in this study for patients undergoing LA, patients with more advanced disease were more likely to have positive margins if they underwent LA vs OA. Moreover, the use of LA in those with stage II ACC decreased OS. Therefore, caution should still be used in selecting LA for surgical treatment of ACC.
Author Contributions
Study conception and design: Huynh, DY Lee, J Lee, Goldfarb
Acquisition of data: Huynh, DY Lee, Lau, J Lee, Goldfarb Analysis and interpretation of data: Huynh, DY Lee, Flaherty, J Lee, Goldfarb
Drafting of manuscript: Huynh, DY Lee, Lau, Flaherty, J Lee, Goldfarb
Critical revision: Huynh, DY Lee, Lau, Flaherty, J Lee, Goldfarb
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