Is 6 cm Diameter an Upper Limit for Adrenal Tumors to Perform Laparoscopic Adrenalectomy?

Abstract

Background:

We aimed to compare the results of patients who underwent laparoscopic adrenalectomy (LA) for masses ≥6 cm versus <6 cm in diameter in our tertiary referral university hospital.

Materials and Methods:

Three hundred thirty consecutive patients were divided into two groups according to tumor size (≥6 and <6 cm in diameter). Demographic variables, body mass index (BMI), lesion localization (right/left), tumor diameter, pathological diagnosis and surgical outcomes, including operation time, estimated blood loss (EBL), conversion to open surgery, complications, and length of hospital stay were compared between groups.

Results:

Between February 2008 and March 2020, 53 patients (29 male–24 female) with ≥6 cm (L group) adrenal tumor and 277 patients (105 male–172 female) with <6 cm tumor (S group) underwent transperitoneal LA. One hundred sixty-eight (50.9%) tumors localized on the left side. In L group mean tumor size in female and male patients was 87.5 ± 40.8 mm (range 50–225 mm) and 67.3 ± 18.4 mm (range 10–100 mm), respectively (P < .05). Age, American Society of Anesthesiology scores, BMI, and mean operation time were similar between groups (P > .05). Postoperative complications were more often in L group (P = .005). EBL in group L and group S was 86 ± 70.4 mL (range 10–500 mL) and 55 ± 44.2 mL (range 10–300 mL), respectively (P = .003). Length of hospital stay in group L and group S was 3.7 ± 3.5 days (range 1–26) and 3 ± 1.6 days (range 1–9), respectively (P = .086). Significant variables in multivariate analysis, including gender (male), EBL, and postoperative complication rate, were entered into multivariate regression analysis, which presented that EBL and postoperative complication rates were independent significants for the L group.

Conclusion:

Six centimeters should not be considered as an upper limit of transperitoneal lateral LA and may be safely performed in centers with experience. Further studies are needed to confirm our data.

Introduction

Laparoscopic techniques have become a standard approach for therapeutic and diagnostic procedure in urology. Laparoscopic adrenalectomy (LA) raises attention of urologists and endocrine surgeons because of the adrenal gland's deep and retroperitoneal location and its minimal invasive nature. Open adrenalectomy requires a wide incision on the abdominal wall and causes higher postoperative morbidity and longer hospitalization.^1,2 LA was first described by Gagner et al. with the experience with 3 patients in 1992.³ The minimally invasive approach has been widely used for the surgical treatment of adrenal masses and considered as the gold standard procedure.^4,5 Comparing to open adrenalectomy, laparoscopic technic provides less blood loss, less postoperative pain, shorter hospital stay, and less morbidity.^5,6 Gagner described lateral decubitus transperitoneal approach; also supine transperitoneal approach, prone retroperitoneal approach, and lateral retroperitoneal approaches are alternatives. It is not clear which approach is more advantageous.^7,8

In terms of laparoscopic approach, upper limit in diameter of the adrenal mass is still controversial in the literature.^4,9–11 In the early times of LA, large masses were considered as relative contraindication for laparoscopic approach. It seems that with the experience gained in LA, large adrenal masses are no longer to be considered as contraindication for laparoscopy.¹² In this study we aimed to compare the perioperative and postoperative outcomes of LA for large (≥6 cm) and small (<6 cm) adrenal masses.

Materials and Methods

Patients diagnosed incidentally or referred to our clinic from Endocrinology department underwent LA with the initial diagnose of adrenal mass. Adrenal lesions suspicious of malignancy in computed tomography scans or magnetic resonance imaging were excluded from the study. Preoperative medication of the patients was arranged in accordance with Endocrinology consultations. All of the cases were performed transperitoneally in lateral decubitus position by three experienced surgeons in a single center. Patients were divided into two groups according to the size of adrenal masses in longest diameter as L (≥6 cm) and S (<6 cm) groups. Patients demographics' (age, gender, body mass index [BMI], American Society of Anesthesiologists [ASA] score), localization of mass (right/left adrenal), mass size, operating time, estimated blood loss (EBL), postoperative complications, length of hospital stay (days), and pathology reports were compared between the L and S groups. The measurement of the pathology specimen was taken as the mass size. The operating time was calculated as the time from entry of the camera and working trocars till closure of the incision after removing the mass from the body.

Skewness and Kurtosis test was used to assess normality. The normally distributed data were presented as mean ± standard deviation, and non-normally distributed data were presented as median value (interquartile range). Univariate analyses were performed between groups using the Student's t-test, Mann–Whitney U test, and Chi-squared test when appropriate. Significant variables on univariate analyses were entered into multivariate logistic regression analyses to determine the independent variables. All statistical procedures were performed with SPSS 23.0 (SPSS Inc, Chicago, Illinois). P < .05 was considered significant. Data obtained in the study were analyzed statistically using SPSS v 22 software (Chicago, IL, USA).

Results

Between February 2008 and March 2020, 330 consecutive patients underwent LA with diagnosis of adrenal mass in our tertiary reference hospital. Two hundred and seventy seven patients (105 male, 172 female) were in S group, and 53 (29 male, 24 female) patients were in L group. Overall, adrenal masses were mostly diagnosed in female patients (n = 196, 59.3%) compared to the male patients (P = .01). One hundred sixty-two right LAs and 168 left LAs were performed. Demographic data of the patients are shown in Table 1.

Table 1.

Outcomes of Group L and Group S

Parameters	L Group	S Group	P
Gender (F/M)	24/29	172/105	.017
Age (mean/min–max)	49.7 ± 12.7/27–77	50.9 ± 12.5/21–88	.55
Tumor size in diameter (cm) (F/M)	87.5 ± 40.8/67.3 ± 18.4	33 ± 12/8–59	N/A
ASA score (ASA ≥3/ASA <3)	8/45	55/222	.274
BMI (kg/m²)(≥30/ < 30)	17/36	112/165	.16
Pathologic diagnosis (benign/malignant)	42/11	237/40	.168
Localization (right/left)	28/25	134/143	.32
Operation time (minutes/min–max)	101.6 ± 39.9/35–180	94.4 ± 35.8/20–210	.25
EBL (mL/min–max)	86.2 ± 70.4/10–300	55 ± 44.2/10–500	.003
Hospitalization (days/min–max)	3.7 ± 3.5/1–26	3 ± 1.6/1–9	.086
Presence of complication	5/48	2/275	.001

Bold values are found to be significant in statistical analysis.

L group: Tumor size ≥6 cm patients, S Group: Tumor size <6 cm patients.

ASA, American society of Anesthesiologists; BMI, body mass index; EBL, estimated blood loss; F, Female; M, Male; max, maximum; min, minimum; NA, not applicable.

On the preoperative evaluation 78 patients had ASA score 1, 189 patients had ASA score 2, 55 patients had ASA score 3, and 8 patients had ASA score 4. Patients were divided into low morbidity (ASA score <3) and high morbidity (ASA score ≥3) groups. In terms of morbidity each group was similar (P = .274).

Mean tumor size in female patients and male patients was 42.8 ± 25.3 mm (range 10–100 mm) and 42 ± 20.3 mm (range 10–225 mm), respectively, and 168 (50.9%) tumors were localized on the left side. In L group mean tumor size in female and male patients was 87.5 ± 40.8 mm (range 50–225 mm) and 67.3 ± 18.4 mm (range 10–100 mm), respectively (P < .05).

For Groups compared in the aspect of BMI ≥30 and BMI <30, both groups (L and S) were similar (P = .161); likewise according to the pathology reports, number of malignant and benign cases were similar between groups (P = .168).

Mean operation time was 101.6 ± 39.9 minutes (range 35–180 minutes) and 94.4 ± 35.8 minutes (range 20–210 minutes) for L group and S group, respectively (P = .25).

Postoperative complication was considered to be within the first 30 days after surgery. Five (9.4%) postoperative complications occurred in L group. Four Clavien Dindo Class (CDC) 1 (mild respiratory distress) and one CDC 4 (intracranial hemorrhage) complications were managed conservatively. Two (0.72%) postoperative complications were presented in S group, including one CDC 2 (bleeding that requires transfusion) and one CDC 3 (pancreatic drainage due to pancreatic injury). Hereby, postoperative complications were seen more often in L group (P = .005).

EBL in group L and group S was 86 ± 70.4 mL (range 10–500) and 55 ± 44.2 mL (range 10–300), respectively (P = .003).

Hospital stay in group L and group S was 3.7 ± 3.5 days (range 1–26) and 3 ± 1.6 days (range 1–9), respectively (P = .086).

In subgroup analysis of L group, ASA score ≥3 patients had significantly larger adrenal lesions than ASA score <3 ones, 8.4 ± 1.3 (7–10) and 7.6 ± 2 (6–15) cm, respectively (P = .03). Similarly ASA score ≥3 patients had significantly prolonged hospital stay compared to ASA score <3 patients, 4.4 ± 1.1 (2–5) and 3.6 ± 3.8 (1–26) days, respectively (P = .01).

According to the pathologic diagnoses, patients were divided into three subgroups benign, malignant, and pheochromocytoma groups. In terms of pathologic diagnoses, group L and group S were similar (P = .168) and, in subgroup analysis of three groups, had similar effects on perioperative and postoperative parameters.

Male gender, EBL, and postoperative complications found significant in univariate analysis were entered into binary logistic regression analysis. In logistic regression analysis, EBL and complication rates were significantly associated with the L group (P < .05) (Table 2).

Table 2.

Logistic Regression Analysis of Gender, Estimated Blood Loss, and Presence of Complication

	Exp (B)	SE	Wald	95% CI for Exp (B) (lower/upper)	P
Gender (male)	1.742	0.316	3.094	0.939/3.23	.079
EBL	1.007	0.003	5.477	1.001/1.013	.019
Presence of complication	0.137	0.937	4.490	0.22/0.862	.034
Constant	0.636	0.983	0.212		.645

CI, confidence interval; EBL, estimated blood loss; SE, standard error.

Discussion

Larger adrenal incidentalomas are diagnosed more commonly with the technologic developments in the imaging modalities. In the literature, cutoff value for adrenal masses is provided as 5–6 cm. Regarding increased risk for malignancy, larger tumors and large adrenal lesions are considered as rare with incidence rates ranging from 8.6% to 38.6%.^{10,11,13–15} Here in this report we present our experience in large adrenal masses managed with transperitoneal laparoscopic technique. Approximately 16% of the patients were presented in L group with tumor size larger than 6 cm. This group of patients had significantly differed from the S group (<6 cm) in terms of preoperative comorbid diseases (P < .05). Tumor pathology, operation technique, perioperative complication rates, and demographic parameters, including age and BMI, were similar in between groups, although male gender, operation time, excess blood loss, postoperative complication rates, and length of hospital stay were increased in the L group. Excess blood loss and postoperative complication rates were significantly higher in the L group (P < .05).

A study from Japan, in patients with BMI >25, has reported that BMI is not associated with unfavorable outcomes in LA.¹⁶ These findings are consistent with the other studies that performed retroperitoneal LA.^17,18 Our study presented similar findings that BMI did not significantly affect perioperative and postoperative parameters in group L and group S.

There is no consensus in the literature that large adrenal masses prolong operation time. Balla et al.¹⁹ and Natkaniec et al.¹¹ reported significantly longer operation time for ≥6 cm adrenal lesions. A recent study noticed that tumor volume is not associated with a difference in operative time.²⁰ Tiberio et al. found that >140 minutes operation time is significantly associated with perioperative complications at multivariate analysis²¹; as a remarkable outcome, mean operative time in both L and S groups was lower than the parameters in Tiberio et al. study. However group L had longer operation time than group S as 101.6 ± 39.9 and 94.4 ± 35.8 minutes, respectively, with insignificant operative outcomes (P < .05).

Nguyen et al. reported that pathologic diagnosis was not associated with a particular side or development of a complication but patients with pheochromocytomas had longer operation time and EBL.²² A similar study reported the diagnosis of pheochromocytoma as an independent factor associated with increased complications.²³

For pheochromocytoma patients Rao et al. reported a longer operative time in a retrospective analysis of transperitoneal LA using a cutoff value of 4 cm, but this difference was not statistically significant.²⁴ In our study, there was no statistically significant difference between the groups in the diagnosis-based subgroup analysis.

Some studies reported 6.7%–9.8% conversion rate for ≥6 cm adrenal lesions and 0.5%–4.9% for <6 cm lesions, and some others reported no conversion to open surgery.^11,12,19 In L group we had no need for conversion to open surgery. In S group only in one case conversion to open surgery was needed because of bleeding. Our low rate of conversion to open surgery may be due to the use of the same technique (lateral transperitoneal) in all patients and the highly experienced adrenal surgeons.

Bleeding is the most common perioperative complication during LA because need to conversion to open surgery is generally due to uncontrolled bleeding. Carter et al. found significant difference in terms of EBL for ≥6 cm versus <6 cm pheochromocytomas (150 mL versus 100 mL; P = .04).¹² A recent study from China reported 100 mL EBL for ≥6 cm lesions.²⁵ Our EBL is in accordance with the literature, however 86.2 ± 70.4 and 55 ± 44.2 mL for group L and group S, respectively (P = .003), and has significant difference between L and S groups. In our opinion this difference depends on anatomical and locational factors. Bigger adrenal lesions tend to have more vein drainage, and especially in the right side, bigger lesions often locate in retrocaval space particularly so dissection may cause more bleeding as we reported before.²⁶

Natkaniec et al. reported close to statistically different complication rates between ≥6 and <6 cm adrenal lesion groups 15.7% versus 9.3% (P = .069).¹¹ Similarly Chung et al. reported high but not significantly different complication rates 33.3% versus 18.5% (P = .47) ≥6 and <6 cm pheochromocytomas, respectively.²⁷ In addition, a recent study noticed higher but not significantly different postoperative complication rates for ≥6 cm lesions.¹⁹ Unlike these, in our study complication rates may be considered similar to other studies but we found statistically significant difference between group L and group S; 9.4% versus 0.72% (P = .005) consistent with a study from Unites States.²³

Chen et al. evaluated that patients with ≥4 cm adrenal tumors experience increased odds of prolonged length of hospital stay²³; likewise, another study reported significantly prolonged length of hospital stay for ≥5 cm adrenal tumors that performed retroperitoneal LA.²⁸ As opposed to this, Carter et al. found comparable length of hospital stay between ≥6 and <6 cm pheochromocytomas.¹² In accordance to Carter et al. and to some authors^19,27,29 we found longer but not statistically significant mean length of hospital stay for group L compared to group S (P = .086). We found significantly increased postoperative complication rates for group L; however, these increased rates did not cause significantly prolonged hospital stay for this group. This can be explained by the fact that the complication scores in the L group are generally low.

Pisarska et al. found ASA score ≥3 related to prolonged length of stay in univariate logistic regression analysis but not in multivariate analysis.³⁰ Similarly a study from United States revealed that being ASA score ≥3 is an independent factor for complication development and also prolongs the operation time.²³ In subgroup analysis in L group, ASA ≥3 patients had longer operation time and larger tumors compared to ASA <3 ones (P = .01 and P = .03, respectively). It should not be considered strange that high comorbidity and bigger lesions may prolong hospital stay.

In our study, gender, bleeding amount, and complication rates found significant in univariate analysis were subjected to binary logistic regression analysis. EBL and complication rate in logistic regression were determined as independent risk factors for LA in the L group. Our study stands out among other studies evaluating LA for large adrenal lesions with the multivariate analysis in the literature and revealing these factors.

In the regression analysis, male gender emerged as an independent risk factor. Although EBL and complication rates were higher in group L, hospital stay, duration of surgery, tumor localization, malignant/benign distinction, ASA score, and age were not observed as significantly different.

Our study has several limitations. First of all retrospective nature and limited number of patients are the main limitations, although other studies in English literature do not have very high numbers of patients either. Absence of control groups with retroperitoneal and anterior transperitoneal approaches may be considered as the lack of the study.

Conclusion

As a conclusion, 6 cm without the suspect of adrenal primary malignancy should not be considered as an upper limit of transperitoneal lateral LA and may be safely performed in centers with experience. Furthermore, large sample size and prospective controlled studies are needed to confirm our data.

Footnotes

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding or grant for research was received.

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