ORIGINAL ARTICLE
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Tumour size in adrenal tumours: its importance in the indication of adrenalectomy and in surgical outcomes-a single-centre experience
C. Mínguez Ojeda1 . V. Gómez Dos Santos1 . J. Álvaro Lorca1 . I. Ruz-Caracuel2 . H. Pian2 . A. Sanjuanbenito Dehesa3 . F. J. Burgos Revilla1 . M. Araujo-Castro4(D
Received: 23 November 2021 / Accepted: 4 June 2022 / Published online: 24 June 2022 @ The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE) 2022
Abstract
Objective To evaluate the relevance of tumour size in adrenal tumours in the estimation of malignancy risk and in the out- comes of adrenalectomy.
Methods We evaluate the histological results and surgical outcomes (intraoperative and postsurgical complications) in a retrospective single-centre cohort of patients without history of active extraadrenal malignancy with adrenal tumours con- secutively operated in our centre during January 2010 and December 2020. We compared these results in lesions smaller and larger than 40, 50, and 60 mm.
Results Of 131 patients with adrenal tumours who underwent adrenalectomy, 76 (58.0%) had adrenal masses measur- ing ≥40 mm; 47 were> 50 mm and 28>60 mm. The final diagnosis was adrenocortical carcinoma (ACC) in 7 patients, pheochromocytoma in 35, and benign lesions in the remaining. All patients with ACC had adrenal masses>50 mm, with Hounsfield units> 40 and low lipidic content in the CT. The risk of ACC and pheochromocytoma increased as tumour size did. The diagnostic accuracy of tumour size was quite good for the prediction of ACC (AUC-ROC 0.883). Nevertheless, when only adrenal tumours with HU <40 were considered, the risk of ACC was 0% independent of tumour size. For pheo- chromocytomas, the risk was of 8.6% independent of tumour size for lesions with <20HU. The risk of intraoperative and postoperative complications was independent of tumour size.
Conclusion Risk of malignancy and of pheochromocytoma increased as tumour size increased, but, in the presurgical estimation of malignancy risk and of pheochromocytoma, not only tumour size, also lipidic content and other radiological features, should be considered. The risk of complications was independent of tumour size, but hospital stay was longer in patients with complication or open approach.
Keywords Adrenal incidentalomas · Tumour size · Adrenalectomy · Adrenocortical carcinoma · Pheochromocytoma
M. Araujo-Castro
☒ marta.araujo@salud.madrid.org
1 Urology Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
2 Pathology Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
3 General Surgery Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
4 Endocrinology and Nutrition Department, Hospital Universitario Ramón y Cajal, IRYCIS, Colmenar Viejo Street, km. 9, 100, 28034 Madrid, Spain
Introduction
The detection of adrenal incidentalomas (AIs) is increasing with widespread use of abdominal imaging [1]. In patients with AIs, the clinician needs to address two important aspects: if the mass is functional and whether it is benign or malignant [2]. Most incidentally discovered adrenal tumours are benign and non-functioning adrenocortical adenomas (ACAs). On the other hand, adrenocortical carcinomas (ACCs) or metastasis are diagnosed in up to 11% of patients with AIs [3]. The risk of malignancy increases in patients with a known active extraadrenal malignancy, being of up to 71% according to some series [4].
In patients with AIs, the risk of malignancy increases with tumour size; in tumours < 40 mm, the risk of malig- nancy is <5% and increases to> 25% for lesions>60 mm. Tumour size of more than 40 mm has a sensitivity of 80-93% for the diagnosis of malignant adrenal mass, and a specificity of 31-61% [5]. Some guidelines recommend adrenalectomy based on tumour size greater than 40-60 mm [1]. Currently, is not recommend an absolute size cut-off for adrenalectomy and it is important to considered other vari- ables when deciding on surgery, including hounsfield units (HU) attenuation on CT, growth or stability on follow-up, age, sex, and comorbidities [2]. Moreover, it is known that surgery is mortality, morbidity and cost associated; thus, it is essential to use the diagnostic tools to assess the risk of malignancy of adrenal mass and decide surgery of hyper- secretory lesions and lesions with significant risk of malig- nancy [6].
The purpose of our study was to evaluate the implica- tions of tumour size in the histological diagnosis of adrenal tumours and in surgical outcomes, including intraoperative and postoperative complications.
Methods
Study population
This was a retrospective cohort study performed at Ramón y Cajal University Hospital, Madrid, Spain, between Janu- ary 1, 2010, and December 31, 2020. This study received approval from the Ethical Committee of the Ramón y Cajal Hospital (approval date: July 2020, ACTA 395). We have followed the STROBE guidelines for the design of our study [7]. All electronic medical records of patients with adrenal tumours underwent adrenalectomy during the study period were individually reviewed for inclusion criteria. Only those patients without history of active extraadrenal malignancy were included. The functional status of adrenal tumours was obtained through medical record review. Hormonal study at the initial evaluation included urinary catecholamines and/or urinary free metanephrines and dexamethasone suppression test (DST). Moreover, urinary free cortisol (UFC), ACTH, age- and sex-adjusted DHEA-S, and late-night salivary cor- tisol were evaluated in some patients according to the physi- cian judgment. For the diagnosis of primary aldosteronism, plasmatic aldosterone concentration and renin concentration or activity was measured. Overt Cushing’s syndrome, pri- mary hyperaldosteronism, pheochromocytoma or androgen excess were diagnosed on the basis of most recent guide- lines [8-10]. Autonomous cortisol secretion was defined as a post-DST serum cortisol> 50 nmol/L (1.8 µg/dL) in the absence of specific clinical features of overt Cushing’s syn- drome [11].
Data were extracted from the electronic medical records system and were collected in an electronic database (RedCAP® database). Information registered in the data- base included demographic, clinical, biochemical, hormonal, and radiological data, anaesthetic risk [American Society of Anaesthesiologists classification (ASA)], and variables related to preoperative, intraoperative, and surgical manage- ment. Medical history of comorbidities at diagnosis includ- ing hypertension, type 2 diabetes mellitus, obesity, dyslipi- daemia, cerebrovascular, and cardiovascular disease, and physical examination variables including body mass index (BMI) and systolic and diastolic blood pressure were also registered. Information about biochemical study including fasting plasma glucose, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, was performed in most of the patients.
Radiological evaluation
All patients underwent unenhanced CT scan and/or MRI examinations at diagnosis. The following image features were extracted from study reports: (1) In CT studies, size (largest reported diameter), uni- or bilaterality, lipid content measured on unenhanced phase on the CT scan, presence of calcifications or necrosis, and HU; and (2) in MRI studies: size (largest reported diameter) and chemical shift imaging [12]. For bilateral AIs, the size of the largest adenoma was included in the analyses. Adrenal tumours were considered rich in lipid content when attenuation was low (< 10 HU) in a CT performed without intravenous contrast [1].
Surgical technique and outcomes
The choice to operate laparoscopically or with an open approach was based on the size of the tumour and the malig- nancy risk of the patient. Laparoscopic surgery was per- formed transperitoneally with the patients placed in lateral position. Open surgery was performed throw transabdomi- nal approach with using of transverse incision just below costal margin. All surgeries were conducted under general anaesthesia. The choice of anaesthetic agent, vasoactive and hypotensive drugs and other additional monitoring were left to the anaesthesiologist’s in charge judgment. Patients were all sent to intensive care unit postoperatively and transferred to ward after haemodynamic variables were stable.
Registered intraoperative complications included intra- operative hypertensive crisis, intraoperative bleeding, pro- longed hypotensive episode, arrhythmias, haemodynamic instability, and others. Postoperative complications were classified in hypertensive crisis, hypotension episode, hypo- glycaemia, acute renal failure, postsurgical ileus and others. They were also classified based on their severity, following the classical Clavien-Dindo scale, considering any deviation
from the normal postoperative course which required phar- macological treatment or interventional procedures, i.e. grade II or higher on the Clavien-Dindo classification [13]. For intraoperative and postoperative complications, we used the same definitions as we have previously described [14, 15].
Histological classification
All specimens were analysed following standardised proto- cols. Briefly, formalin-fixed specimens were macroscopi- cally examined, and tumour sized was measure in mm. A minimum of one block per 10 mm was obtained for histo- logical study. Diagnoses were stablished following WHO classification of Tumours of Endocrine Organs (4th edition, 2017). In addition to haematoxylin-eosin, reticulin histo- chemistry was performed in adrenocortical neoplasms. When necessary, immunohistochemical panels were used to differentiate primary from metastatic tumours, and corti- cal from medullary neoplasms. In adrenocortical neoplasms, Weiss criteria were applied to differentiate adenomas from ACC [16]. Benign and malignant oncocytic adrenocortical neoplasms were differentiated according to Lin-Weiss-Bis- ceglia criteria [17].
Statistical analysis
The statistical analysis was performed using STATA.15. Normality assumption was checked using Shapiro-Wilk test. Categorical variables are expressed as percentages and absolute values and quantitative variables as mean ± stand- ard deviation or median and ranges depending on the normal distribution of the variable. When data were missing for a variable, the number of patients analysed were indicated. Logistic regression model was used for the estimation of the odds ratios (OR) and 95% confidence intervals. The chi2 test was performed for the comparison of categorical variables between independent groups and the t-test for comparison between means. For quantitative variables reaching statis- tical significance in the comparisons, receiver operating characteristics curve (ROC) analysis was used as a measure of diagnostic accuracy, and to identify the cut-off values showing the best combination of sensitivity and specificity. In all cases, a two-tailed p value <0.05 or a 95% confidence interval of the OR not including the number 1, were consid- ered statistically significant. Pearson’s correlation coefficient was performed.
Results
Baseline characteristics
Of the 131 patients with adrenal tumours included in the study, 57.5% were women and the mean age at diagnosis was of 55.3 +13.51 years old. The main indications of surgery were overt Cushing’s syndrome in 14, pheochromocytoma in 35, primary aldosteronism in 27, ACS in 8 and tumour size greater than 40 mm and/or atypical features in the remaining. Moreover, there were 14 patients with adrenal lesions that have experienced a growth> 5 mm in less than 6 months. In total, 76 (58.0%) had adrenal masses measuring 40 mm or more in diameter; 47 were equal or larger than 50 mmm and 28 equal or larger than 60 mm. Most patients with diagnosis of pheochromocytomas were discovered in the context of the study of an AI (n=32), but there were three patients with typical clinical symptoms of catecholamine hypersecretion at diagnosis. Regarding patients with ACC, no evidence of metastasis was observed in any case at diagnosis. Baseline characteristics of the patients are reported in Table 1.
Tumour size and histological results
The final histological results were ACC in 7 patients, ACA in 77, pheochromocytoma in 35, cortical hyperplasia in 8 and myelolipoma in 4. All patients with histological diagno- sis of ACC were adrenal masses greater than 50 mm (median tumour size: 78 mm, range 50-170) and had Hounsfield units> 40 [median 70 (range 43-150) and low lipidic con- tent in the CT. Moreover, 57% of them had necrosis or calci- fications in the CT. The risk of ACC and pheochromocytoma increased as tumour size did (MH Test for linear Trend: Chi2(1)=13.26; p=0.0003] (Table 2). Nevertheless, when only adrenal tumours with HU <40 was considered, the risk of ACC was 0% independently of tumour size. In this way, the risk of ACC was 0% for adrenal lesions with < 40UH, 18.2% for adrenal lesions with> 40 UH. Nevertheless, for pheochromocytomas, the risk was close to 0% independently of tumour size for lesions with <20 HU (only 3 patients with pheochromocytomas had HU <20: 10, 15 and 14 HU). We found that the diagnostic accuracy of tumour size was quite good for the prediction of ACC (AUC-ROC: 0.883 [0.796-0.970]), being the cut-off of 56 mm the one that offered the highest diagnostic accuracy (Sensitivity 85.7%, specificity 80.6%). However, the positive predictive value of this threshold was as low of 20%, but the negative predic- tive value was of 99%. In fact, the variables strongly associ- ated with the risk of ACC were necrosis and HU (Table 3). Tumour size was a poor predictor of pheochromocytoma, being 41 mm the threshold that offered the highest diagnos- tic accuracy (Sensitivity 74.3%, specificity 55.2%) (Table 4
| Variable | % (n) |
|---|---|
| Age (years) | 55.3±13.51 |
| Women | 57.5% (75) |
| Type 2 diabetes | 26.0% (34) |
| Obesity | 5.3% (7) |
| Hypertension | 60.3% (79) |
| Functionality | 64.1% (84) |
| DST in ACS and CS (nmol/L [ug/dL]) | 219.9±201.44 [7.7±7.30] |
| Urinary free cortisol in CS (nmol/24 h [ug/24 h]) | 4327.5±5166.02 [156.9±187.24] |
| Urinary free metanephrine in PHEO (ug/24 h) | 2212.1±6252.81 |
| Urinary free normetanephrine in PHEO (ug/24 h) | 219.7±229.94 |
| Tumour size (mm) | 45.4±29.58 |
| Tumour size ≥ 40 mm | 58.0% (76) |
| Tumour size ≥ 50 mm | 35.9% (47) |
| Tumour size ≥ 60 mm | 21.4% (28) |
| Bilaterality | 4.6% (6) |
| Calcifications in CT (n=118) | 16.1% (19) |
| Necrosis in CT (n=118) | 8.5% (10) |
| Low lipidic content (n=117) | 94.0% (110) |
| Hounsfield Units (n=87) | 46.1±42.52 |
| Hounsfield Units> 10 (n=87) | 88.5% (69) |
| Hounsfield Units <40 (n=87) | 54.0% (47) |
CS: Cushing’s syndrome; DST: dexamethasone suppression test. Normal ranges: for urinary free cortisol: < 140 µg/24 h; for urinary free metanephrine: < 1000 µg/24 h; for urinary free norme- tanephrine < 800 µg/24 h
| Tumour size (mm) | Risk of ACC | Risk of PHEO | Risk of ACC if HU<30 | Risk of PHEO if HU<30 |
|---|---|---|---|---|
| <40 | 0% (0/55) | 12.7% (7/55) | 0% (0/17) | 11.8% (2/17) |
| 40-50 | 0% (0/29) | 34.5% (10/29) | 0% (0/6) | 16.7% (1/6) |
| 50-60 | 10.5% (2/19) | 31.6% (6/19) | 0% (0/6) | 33.3% (2/6) |
| >60 | 17.9% (5/28) | 42.9% (12/28) | 0% (0/7) | 0% (0/7) |
ACC adrenocortical carcinoma, PHEO pheochromocytoma, HU Hounsfield units
| Variable | Odds ratio [95% confident interval] |
|---|---|
| Age (years) | 1.03* [0.97-1.11], p=0.269 |
| Tumour size (mm) | 1.03* [1.01-1.05], p=0.003 |
| Calcifications in CT | 1.01 [0.64-1.78], p=0.809 |
| Necrosis in CT | 11.14 [2.07-59.86], p=0.010 |
| Hounsfield units >40 in CT | NC |
| Bilaterality | NC |
| Loss of signal in phase opposi- tion in MRI | 0.32 [0.02-5.59], p=0.418 |
*Per each increased in unit. NC: not calculable, as all ACC were bilateral and had HU>40
| Tumour size | ACC | PHEO |
|---|---|---|
| <40 mm | 0% (0/7) | 20% (7/35) |
| 40-50 mm | 0% (0/7) | 28.6% (10/35) |
| 50-60 mm | 28.5% (2/7) | 17.1% (6/35) |
| >60 mm | 71.5% (5/7) | 34.3% (12/35) |
and Fig. 1). There was a strong positive correlation between the radiological tumour size and the histological size of the tumour (r=0.906, p<0.0001).
Tumour size and surgical outcomes
Most patients underwent unilateral laparoscopic adre- nalectomy (n= 102), followed by unilateral open adre- nalectomy in 24, bilateral laparoscopic adrenalectomy in 3 and bilateral open surgery in 2. Mean tumour size was of 71.4 ±48.57 mm in adrenal tumours underwent open adrenalectomy, and 38.8 ± 17.74 mm in those submitted to laparoscopic approach (p=0.024). Reconversion to open adrenalectomy was necessary only in 3 patients: in one cortisol secreting adrenal adenoma of 17 mm and another non-secreting adrenal adenoma of 45 mm, due to adhesions
A1)
TUMOUR SIZE AS PREDICTOR OF ACC
1.00
A2)
HOUNSFIELD UNITS AS PREDICTOR ACC
1.00
Sensitivity
0.75
Sensitivity
0.75
0.50
0.50
AUC = 0.771
0.25
AUC= 0.883
0.25
0.00
0.00
0.00
0.25
0.50
1.00
0.00
0.25
0.50
1 - Specificity
0.75
1 - Specificity
0.75
1.00
B1)
TUMOUR SIZE AS PREDICTOR OF PHEO
B2)
HOUNSFIELD UNITS AS PREDICTOR PHEO
1.00
1.00
Sensitivity
0.75
Sensitivity
0.75
0.50
0.50
AUC = 0.685
AUC= 0.728
0.25
0.25
0.00
0.00
0.00
0.25
0.50
1 - Specificity
0.75
1.00
0.00
0.25
0.50
1 - Specificity
0.75
1.00
| Tumour size (mm) | Risk of intraoperative complications* | Risk of postop- erative complica- tions ** |
|---|---|---|
| <40 | 7.3% (4/55) | 4.3% (2/47) |
| 40-50 | 10.3% (3/29) | 3.7% (1/27) |
| 50-60 | 16% (3/19) | 11.1% (2/18) |
| >60 | 14.3% (4/28) | 11.1% (3/27) |
*MH Test for linear Trend: Chi2(1)=1.34 (p=0.2464); ** MH Test for linear Trend: Chi2(1) 1.76 (p=0.1848)
and in a pheochromocytoma of 42 mm due to a lesion of the renal vein. An open approach was performed in 12.7% of adrenal tumours <40 mm (7/55); 6.9% of lesions between 40 and 50 mm (2/29); 21.1% of tumours of 50-60 mm (4/19) and in 46.4% of lesions > 60 mm (13/28).
Overall, 10.7% (n=14) of the patients experienced any intraoperative complication, being bleeding the most fre- quent (n=8). Postsurgical complications were recorded in 6.7% (n=8) of the patients, being haemodynamic insta- bility the most frequent (n =2). The risk of intraopera- tive and postoperative complications was independent of tumour size (Table 5). However, there were a tendency to an increase in complications as tumour size increased, since 10.9% of tumours of < 40 mm experienced complica- tions (intraoperative or postsurgical) compared to 28.6% of tumours greater than 60 mm (p=0.059). Intraoperative and
postsurgical complications were more common in patients underwent open adrenalectomy than laparoscopic surgery (23.1% vs 7.6%, p=0.022 and 21.7% vs 3.1%, p=0.001, respectively). Hospital stay was longer in patients expe- rienced intraoperative or postsurgical complications than without (5.8±4.31 vs 3.4±1.35 days, p=0.037), and in those patients underwent open approach than laparoscopic surgery (5.0±3.12 vs 3.4±1.82 days, p=0.029).
Discussion
The aim of this study was to investigate the relevance of tumour size in the estimation of malignancy risk and in the outcomes of adrenalectomy. The main findings of our study were that all patients with histological diagnosis of ACC were adrenal masses greater than 50 mm and with more than 40 U Hounsfield units in the CT scan. Although the diagnostic accuracy of tumour size was quite good for the prediction of ACC (AUC-ROC: 0.883), based on the optimal cut-off, the positive predictive value was as low of 20%. In this way, other radiological characteristics as Hounsfield units should be considered for the estimation of malignancy risk. In adrenal lesions with <40UH the risk of ACC was 0% independently of tumour size. Similarly, the risk of pheo- chromocytoma was close to 0.1% independent of tumour size for lesions with < 30HU.
As expected, the adrenal cancer risk observed in our study increased as lesion size increased. In accordance with
our results, a previous study reported that the risk of ACC is less than 2% in patient with tumours < 40 mm, 6% between 40 and 60 mm and increase to 25% in large adrenal tumours (>60 mm) [18]. Moreover, in a multicenter study of 1096 patients with AIs, a tumour size threshold of at least 40 mm distinguished ACC from benign adrenal tumours with a sen- sitivity of 93% but a specificity of only 42% [19]. These results are in line with ours, as 100% of ACC in our series were higher than 50 mm, being 56 mm the optimal threshold to differentiate benign lesions and ACC. However, in our study this cut-off offered a lower sensitivity (85.7%) but a notably higher specificity (80.6%).
ACC is an aggressive disease with a poor prognosis, at the time of diagnosis, 26.5% of patients will have metastases and 5-year survival rates range between 35 and 40%. Thus, it is important to achieve an early diagnosis of ACC because the consequences of a missed ACC in small tumours might be considerably, since the only curative treatment is com- plete surgical resection [20]. The imaging characteristics of ACC are important to distinguish it from benign ACA. CT density > 10 UH has a high sensitivity for detection adrenal malignant tumours; however, 30% of benign tumours are “lipidic-poor” with an attenuation > 10 UH on CT. In these cases, it is important to consider other imaging and clinical characteristics. For example, necrosis is uncommon in ACA, and it is present in up to 5-10% of ACC, similarly irregular margins and calcifications are a relatively common finding in ACC, while is anecdotally reported in ACA. Moreover, Hounsfield units hardly ever reached 40 UH in ACA, even in poor lipidic ACA, whereas a value of 40 HU or higher is reported in up of 80-90% of ACC [21]. Thus, we consider that Hounsfield units that reveals the lipidic content of the adrenal tumour is a crucial parameter to evaluate when the risk of malignancy is estimated, not only the tumour size. As we can observed in our results, the risk of ACC was 0% when only lesions <30 HU were evaluated, independently of tumour size. These results suggest that lipidic content is even a more accurate radiological characteristic to differenti- ate benign and malignant adrenal tumours than tumour size. Nevertheless, it is important to take into account that up to 30% of adrenal lipid-poor adenomas may have a borderline- malignant potential at histopathology [22]. A more recent tool for adrenal characterisation is the CT texture analysis. A recent meta-analysis [23] described an area under the ROC curve of 0.85 of the texture analysis, depicting a high diagnostic accuracy, up to 93% in differentiating ACA from ACC. Another important point to consider for predicting the behaviour of the adrenal mass is the hormonal status, as it is reported that the steroid pattern may indicate whether an adrenal lesion is an ACC. Moreover, hormonal evaluation is of prognostic value as cortisol-secreting tumours generally have a worse prognosis [24].
Pheochromocytomas were the second most frequent diagnosis (27%) in our cohort patients, 80% of pheochro- mocytomas were greater than 40 mm and 100% had an attenuation > 10 UH on CT, and only 3 patients had < 20 UH. These findings are in accordance with several previ- ous studies in which the mean of density in pheochro- mocytomas was 38.6 UH and all PHEOs demonstrated attenuation more than 10UH [25]. Because there were 20% of pheochromocytomas smaller than 40 mm, it is essen- tial to biochemically exclude PHEO, especially in AIs with indeterminate imaging characteristics independently of a tumour size. However, when high lipid content was combined with a small tumour size (<20 mm), the prob- ability that an adrenal lesion was a pheochromocytoma is reported to be less than 0.1%, so the biochemical screen- ing to rule out pheochromocytoma may be spared in these adrenal lesions [26]. Nevertheless, assessment of UH may be less reliable in patients with cortisol-secreting adeno- mas, since some authors reported a reduced lipid content according to the increase of cortisol secretion [27].
The majority of adrenal resections are performed via laparoscopic approach, the open surgical approach should be considered for tumours demonstrating features suspi- cious for malignancy such as large tumour size (> 100 mm) or radiographic evidence of adjacent organ or vascular invasion, the use of laparoscopic surgery for the treat- ment of known or suspected ACC is controversial, should only be undertaken by experienced laparoscopic surgeons and if a complete en bloc resection of the mass without adrenal capsular rupture is in doubt, conversion to an open approach is advised [28]. In this way, a recent study that includes 529 patients who underwent adrenalectomy, found that adrenal lesions measuring ≥ 40 mm are not a contraindication for laparoscopic adrenalectomy neither in terms of cancer risk nor of conversion and morbidity rates, even if the operative time increases with increasing adre- nal lesion diameter [29]. Chen et al. reported that patients with adrenal tumours greater than 40 mm experience more perioperative complications and prolonged length of hos- pitalisation [25]. Other studies described a significantly prolonged hospital stay and postoperative complications for adrenal tumours > 50 mm [26, 30]. In contrast, our results revealed that the risk of intraoperative and post- operative complications was independent of tumour size, Accordingly, other studies didn’t found differences in postoperative complications according to tumour size, but rather patient’s medical history, whether it is a hormone- secreting tumour or the surgical approach, which could be conditioned by the tumour size, are more important risk factors that are related to complications [31]. In our study, hospitalisation was longer in patients who experienced intraoperative or postsurgical complications, and in those patients, that underwent open approach. Similar findings
were reported in other studies that suggest postoperative complications occurred more often in open surgeries com- pared with laparoscopic approach, this could be explained because open adrenalectomy require a wide incision on the abdominal wall and causes higher postoperative morbid- ity and longer hospitalisation [32]. Moreover, the size of the adrenal tumour is not the exclusive variable affecting the clinical outcomes, other parameters (BMI, operating time, duration of procedure > 140 min, ASA> 3) were also associated with increased postoperative complications and length of hospitalisation [33].
It is important to note that our study has several limita- tions. First, its retrospective nature and a long-lasting study period. Second, it is an unicentral study with a reduced group of adrenalectomies, as in most of the published series. The small number of malignant lesions (only 7 patients with ACC) may affect the statistical analysis. Moreover, we are aware that the radiological evaluation of an adrenal mass is not so easy, and a close collaboration with an adrenal dedi- cated radiologist is required for a correct characterisation [34]. For this reason, our results may not be totally extrapo- lated to other centres that do not have specialised radiolo- gists. To solve these limitations, it is important for future studies to carry out a prospective multicenter study, with a large cohort to confirm our findings.
Conclusions
The risk of malignancy and of pheochromocytoma increased as tumour size increased, but for adrenal tumours with HU <40, the risk of ACC was 0% independently of tumour size; and for adrenal tumours with HU <20, the risk of pheo- chromocytoma was lower than 10% independently of tumour size. Thus, in the presurgical estimation of malignancy risk, not only tumour size, also lipidic content and other radio- logical features, should be considered. The risk of complica- tions was independent of tumour size, but hospital stay was longer in patients who experienced surgical complications or who underwent open approach.
Funding SENDIMAD: BECA SENDIMAD de Ayuda a la Inves- tigación en Endocrinología, Nutrición y Diabetes 2019. IRYCIS: Convocatoria intramural de ayudas a proyectos de investigación de investigadores noveles, investigadores clínicos asociados y/o grupos emergentes del Hospital Universitario Ramón y Cajal 2019.
Declarations
Conflict of interest The authors have no conflict of interest.
Ethical approval All procedures performed in the participants of the study were in accordance with the ethical standards of the institutional
research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent Patient consent was waived due to the retrospec- tive nature of the study. Only for patients who continued follow-up or prospectively included the informed consent was requested.
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