ORIGINAL ARTICLE
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Tailored surgery for large adrenal tumors: the minimally invasive to open (hybrid) approach
Agata Dukaczewska1 . Konrad Ilgner1 . Catarina Alisa Kunze2 . Jennifer Sladek1 . Eva Maria Dobrindt1 . Peter E. Goretzki1,3 . Johann Pratschke1 . Martina T. Mogl1 . Frederike Butz1 (D
Received: 23 April 2025 / Accepted: 18 August 2025 / Published online: 29 August 2025 @ The Author(s) 2025
Abstract
Conversion from minimally invasive techniques to open surgery has mostly been considered as an undesirable event associ- ated with intraoperative complications or poor preoperative planning. However, the impact of conversion to open surgery during adrenalectomy for large adrenal tumours remains unclear. This study investigates the outcomes of conversion from minimally invasive to open surgery for adrenal masses ≥60 mm with an additional focus on the identification of survival predictors in patients with large adrenocortical carcinoma (ACC). We retrospectively analyzed 97 patients who underwent unilateral adrenalectomy for tumours ≥60 mm. Patient characteristics, tumour features, surgical approaches, and outcomes were compared. Survival outcomes in ACC patients (n=34) were assessed using Kaplan-Meier analysis, with prognos- tic factors evaluated via univariate Cox regression and Ridge Regression modeling. Of 97 patients, 41 (42%) underwent minimally invasive adrenalectomy (MIA), 40 (41%) open adrenalectomy (OA), and 16 (17%) required conversion to open surgery (hybrid adrenalectomy, HA). HA had a longer operative time (median 226.5 vs. 108.5 min; p <0.001) and hospital stay (median 9 vs. 4 days; p<0.001) compared to MIA but not OA (median 188 min; p=0.102; 10 days; p=0.519, respec- tively). Overall, complications were more frequent in HA (43.7%) than MIA (7.3%; p=0.003) but similar to OA (37.5%; p=0.897). Minor complications were more common in HA than MIA (31 vs. 7%; p=0.032), while major complications were comparable (12.5 vs. 7.5%; p=0.617). Tumours in HA cases more often showed vascular infiltration (p=0.001) and required multivisceral resection (p=0.002). ENSAT tumour stage (OS: HR=4.66, p=0.041; PFS: HR =2.52, p=0.005) and the S-GRAS score (OS: HR =6.00; PFS: HR = 1.50) were significant survival predictors in ACC, whereas the opera- tive technique was not. Conversion to open surgery increases minor complications compared to MIA but not OA. ENSAT tumour stage and S-GRAS score predict survival in ACC, while the surgical approach does not. Timely conversion should be performed to ensure oncological safety when needed.
Keywords Adrenalectomy · Conversion · Large adrenal tumours
Martina T. Mogl and Frederike Butz contributed equally to this work.
☒ Frederike Butz frederike.butz@charite.de
1 Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt- Universität zu Berlin, 10117 Berlin, Germany
2 Department of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
3 Department of Endocrine Surgery, Helios Universitätsklinikum Wuppertal, Universität Witten-Herdecke, Heusnerstraße 40, 42283 Wuppertal, Germany
Introduction
While minimally invasive techniques are currently the gold standard in the treatment of non-invasive adrenal tumours measuring less than 60 mm [1-4], open adrenalectomy is recommended when malignancy and local invasion is suspected to prevent rupture of the tumor capsule [2, 5]. However, as surgical experience with minimally invasive procedures for adrenal tumours continues to grow, the indications for laparoscopic adrenalectomy have expanded [6-8]. When minimally invasive surgery is applied to large adrenal tumours, the possibility or necessity of conversion to open surgery should be evaluated. To date, conversion has mostly been seen as an undesirable event associated
with intraoperative bleeding [9] and an elevated rate of R1 resections [10]. Large tumour size, histological type (pheo- chromocytoma or malignant tumour) and the need for mul- tivisceral resection [6, 11, 12] were identified as risk factors for conversion at the planning stage of the operation thereby justifying an open surgical approach [11]. The implications of conversion, however, have not been sufficiently investi- gated. Studies on conversion are scarce and yield contradic- tory results [6, 9, 13]. As conversion is an important secu- rity measure that should consciously be applied to prevent undesirable intraoperative events [4], there is an urgent need to reduce bias towards it. Furthermore, a hybrid technique that involves a planned transition from minimally invasive to open surgery may be selected in specific cases to benefit from both approaches within a single operation [14].
We conducted the current study to retrospectively evalu- ate the impact of conversion on operative and postoperative outcomes in the surgical treatment of large adrenal tumours in patients treated at the tertiary centre for endocrine surgery of Charité - Universitätsmedizin Berlin .
Materials and methods
Patient demographic and clinical data
468 consecutive patients who underwent adrenalectomy from January 2008 to April 2023 at the tertiary centre of endocrine surgery of Charité - Universitätsmedizin Berlin were included in a retrospective database. Patients who underwent bilateral adrenalectomy (n=12), who had prior surgery on the ipsilateral or contralateral adrenal gland (n=9), or who were operated on for adrenal haematoma were excluded from the study. Finally, patients who under- went unilateral surgery for an adrenal tumour measuring at least 60 mm (n=97) were retrieved from the database and assigned to three groups on the basis of the surgical tech- nique used for adrenalectomy: minimally invasive (MIA), open (OA) and hybrid adrenalectomy (HA), the latter including conversion from a minimally invasive to an open approach. None of the tumors in this cohort were resected using a robotic technique. The abovementioned surgical approaches were compared with respect to patient-specific factors (patient age, sex, body mass index (BMI) and physi- cal status according to American Society of Anaesthesiolo- gists (ASA) classification), tumour-specific factors (tumour type, size, and location, presence of vascular and/or adjacent organ infiltration and lymph node metastases, hormone pro- duction), intraoperative and postoperative outcomes (dura- tion of surgery, necessity of multivisceral resection, need for intraoperative or postoperative blood transfusion, require- ment for postoperative intensive care unit (ICU) monitoring, length of stay in the ICU and postoperative hospital stay)
and occurrence of postoperative complications according to the Clavien-Dindo classification [15], with minor complica- tions including all 1-3a complications and major complica- tions greater than or equal to 3b. The reasons for conversion in the HA group were retrieved from surgical reports. The S-GRAS score [16], encompassing sex, grade (according to the European Network for the Study of Adrenal Tumours (ENSAT) system), resection status, age, and tumour-related symptoms, was calculated for all ACC patients. The study was conducted in accordance with the principles of the Dec- laration of Helsinki, and institutional review board approval was obtained (EA1/394/20, 21 January 2021).
Statistical analysis
Continuous variables are displayed as medians (range), cat- egorical variables as frequencies. The Mann-Whitney U test was used for group comparison of metric variables, the chi- square or Fisher’s exact test for categorical variables. The Kaplan-Meier method was used to calculate overall survival (OS), defined as time between adrenalectomy and death and progression-free survival (PFS), defined as time between adrenalectomy and first postoperative progression in patients with adrenocortical carcinoma. Patients who did not reach the respective endpoints or were lost to follow-up were cen- sored at the last follow-up visit. Patients without follow- up were excluded from the PFS and OS analyses. Survival rates were compared using log-rank tests. The prognostic value of variables was assessed with univariate Cox regres- sion models. R1 and Rx categories were pooled to improve model stability due to small samples. To address multicol- linearity and model instability, a multivariate analysis was performed using the Ridge Regression model with regulari- zation parameter 2 =0.0174 applied for OS and 2=0.4551 for PFS. The significance level was set to 0.05. Statistical analyses were performed using R version 024.12.0+467 (R Foundation for Statistical Computing, Vienna, Austria).
Results
Patient and adrenal tumour characteristics
During the observation period, a total of 97 patients under- went surgery for an adrenal tumour measuring at least 60 mm. While the most common indications for surgery included adrenocortical carcinomas (n=33, 34%), pheo- chromocytomas and paragangliomas (n=23, 23.7%), and adrenocortical adenomas (n=19, 19.6%), other indications (n=7) included single cases of an oncocytoma, sarcoma, fibroma, schwannoma, B-cell-Hodgkin lymphoma, gangli- oneuroma, and haemangioma. Approximately one-quarter of the lesions infiltrated blood vessels (n=25, 25.8%) while
only a small portion of tumors (n=5, 5.2%) exhibited infil- tration into adjacent organs (kidney, liver, diaphragm, and lymph node). The characteristics of the study cohort are summarized in Table 1.
Intra- and postoperative outcomes of the study cohort
As shown in Table 2, 41 (42.3%) operations were con- ducted as MIA (38 via transperitoneal and 3 via retroperi- toneoscopic approach), 40 (41.2%) as OA and 16 (16.5%) as HA. The transperitoneal laparoscopic approach was indicated due to suspected benign tumours (n = 18, 47%) or pheochromocytomas (n=9, 24%). The retroperitoneo- scopic approach was chosen in one case due to a sus- pected benign tumour (n = 1, 33.3%) and in another due to suspected adhesions after previous transabdominal
operations (n= 1, 33.3%). In 11 patients (29%) oper- ated on via transabdominal laparoscopy and in 1 patient (33.3%) via the retroperitoneoscopic approach, no expla- nation was provided in the operation report or discharge letter.
Open surgery was performed due to suspected malig- nancy (n=5, 12.5%), suspected organ infiltration (n=2, 5%), planned multivisceral resection (n=20, 50%), large tumour size (n = 8, 20%), suspected adhesions after abdominal operations (n= 1, 2.5%), and, in one patient (2.5%), due to heart insufficiency as a contraindication to laparoscopy. In 3 patients (7.5%) who underwent open surgery, no reason was documented in the operation report.
Planned hybrid adrenalectomy was chosen in 8 (89%) patients to achieve maximum tumour mobilisation lapa- roscopically before conversion, and in 1 (11%) patient because laparoscopic resection of a liver metastasis was
| Genderª | Female | 51 (52.6%) |
| Male | 46 (47.4%) | |
| Age (years)b | 57 [18-86] | |
| BMI (kg/m2)b (n.a .= 3) | 26.3 [17.9-78] | |
| ASAª | 1 | 6 (6.2%) |
| 2 | 40 (41.2%) | |
| 3 | 48 (49.5%) | |
| 4 | 3 (3.1%) | |
| Tumour sideª | Right | 42 (43.3%) |
| Left | 55 (56.7%) | |
| Tumour size (mm)b | 84 [60-260] | |
| Hormonal activityª (n.a .= 1) | 60 (62.5%) | |
| Tumour entityª | Adrenocortical carcinoma | 33 (34.0%) |
| Adrenocortical adenoma | 19 (19.6%) | |
| Adrenal metastasis | 12 (12.4%) | |
| PPGL | 23 (23.7%) | |
| Adrenal cyst | 3 (3.1%) | |
| Other | 7 (7.2%) | |
| Lymph node metastasesª | 8 (8.2%) | |
| Vascular infiltrationª | 25 (25.8%) | |
| Infiltration of adjacent organsª | 5 (5.2%) | |
| Hormonal activity | Hormonally inactiveª | 37 (38%) |
| Catecholaminesª | 20 (21%) | |
| Cortisolª | 15 (16%) | |
| Aldosteroneª | 7 (7%) | |
| Androgen-related steroids1 | 4 (4%) | |
| Cortisol + Androgen-related steroidsª | 13 (13%) | |
| Cortisol + Catecholaminesª | 1 (1%) |
BMI Body Mass Index, ASA American Association of Anesthesiologists, n.a. not available, PPGL phaeo- chromocytoma and paraganglioma, ICU Intensive Care Unit
ªCount (percentage)
bMedian [range]
Table 2 Intra and postoperative outcomes after surgery for adrenal tumours measuring ≥60 mm (n=97)
Intra and postoperative course
| Technique of operationª | Minimally invasive | 41 (42.3%) |
| Open surgery | 40 (41.2%) | |
| Hybrid approach | 16 (16.5%) | |
| Duration of surgery (minutes)b (n.a .= 4) | 148 [52-825] | |
| Multivisceral resectionª | 27 (27.8%) | |
| Blood transfusionª | 13 (13.4%) | |
| ICUª | 62 (63.9%) | |
| Length of postoperative ICU stay (days)b | 1 [0.5-38] | |
| Length of postoperative hospital stay (days)b | 6 [1-78] | |
| Complications (any)ª | 25 (25.8%) | |
| Type of complicationsª | Minor | 20 (20.6%) |
| Major | 5 (5.2%) |
n.a. not available, ICU Intensive Care Unit
ªCount (percentage)
Median [range]
planned. No specific reason for laparoscopic exploration was documented in the group of patients with unplanned conversion.
Characteristics of patients undergoing hybrid adrenalectomy
As the study focused on the impact of conversion on intra- and postoperative outcomes, we provided a detailed description of the HA group (Table 3). Sixteen patients
| Patient | Age | Gender | ASA | BMI (kg/m2) | Side | Size (mm) | Pathology | Reasons for conversion | Planned conver- sion |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 74 | M | 3 | 32,4 | R | 60 | META | Infiltration of the liver | No |
| 2 | 58 | F | 2 | 28.4 | R | 60 | META | Infiltration of the vena cava inferior | No |
| 3 | 59 | M | 3 | 26.5 | L | 95 | PHEO | Poor anatomical overview due to tumour size | No |
| 4 | 70 | F | 2 | 30.0 | R | 60 | ACC | No laparoscopic preparation possible due to stretching of the vena cava inferior over the tumour | No |
| 5 | 35 | F | 4 | 24.3 | L | 120 | PHEO | Adhesion to pancreas and kidney; Poor anatomical overview due to tumour size | Yes |
| 6 | 64 | F | 3 | 41.1 | R | 65 | ACC | Elevated risk of capsule injury (thin capsule) | Yes |
| 7 | 58 | M | 2 | 26.9 | R | 85 | ACC | Adhesion to the kidney; Poor anatomical overview due to tumour size | Yes |
| 8 | 39 | M | 2 | 25.7 | L | 75 | PHEO | Adhesion to the kidney | No |
| 9 | 72 | M | 3 | 31.0 | L | 130 | ACC | Adhesion to the kidney | Yes |
| 10 | 49 | M | 3 | 21.7 | L | 105 | PHEO | Adhesion to pancreas | Yes |
| 11 | 29 | M | 1 | 29.2 | L | 65 | SARCOMA | Adhesion to kidney | No |
| 12 | 61 | F | 2 | 29.7 | R | 67 | ACC | Adhesion to the liver, elevated risk of capsule injury (soft tumour) | Yes |
| 13 | 70 | M | 3 | 24.2 | L | 85 | META | Poor anatomical overview due to tumour size | No |
| 14 | 60 | M | 3 | 35.7 | L | 88 | ACA | Adhesion to the kidney | Yes |
| 15 | 49 | M | 3 | 28.1 | L | 130 | ACC | Adhesion to the kidney | Yes |
| 16 | 63 | F | 3 | 27.3 | L | 133 | ACC | Poor anatomical overview due to tumour size | Yes |
M male, F female, ASA American Association of Anesthesiologists classification, BMI body mass index, R right, L left, META adrenal metasta- sis, PHEO pheochromocytoma, ACC adrenocortical carcinoma, ACA adrenocortical adenoma
underwent surgery via a hybrid approach; in nine patients (56%), conversion was implemented as a planned strategic manoeuvre during the surgical procedure. The indications for surgery included adrenocortical carcinoma (n=8), pheochromocytoma (n=4), adrenal metastasis (n=3) of a leiomyosarcoma, non-small cell lung cancer, hepa- tocellular carcinoma, and one case of sarcoma. In each patient, maximum tumour mobilization was reached lapa- roscopically before conversion. The reasons for conver- sion included adhesions to or infiltration of other organs (liver pancreas and/or kidney) or blood vessels and a poor anatomical overview due to the tumour size.
Outcome according to the surgical technique used for adrenalectomy: comparison of the three groups
The number of female patients in the OA group was sig- nificantly greater than that in the MIA group (n=28, 70% vs. n= 17, 41% p=0.018). Moreover, no differences in age, BMI and ASA of the patients were found among the 3 groups, as presented in Table 4.
In the OA and HA groups, a significantly greater pro- portion of diagnoses of adrenocortical carcinoma were con- firmed than in the MIA group (n=23, 57.5% (p<0.001) and n=7, 43.75% (p=0.003) versus n=3, 7.3%, respec- tively). Conversely, minimally invasive adrenalectomies were performed more often for adrenal adenoma (n=15, 36.6%) than open (n=3, 7.5%) and hybrid adrenalecto- mies (n=1, 6.25%); (p<0.001 and p=0.023, respectively).
| MIA (n=41) | OA (n=40) | HA (n=16) | p Value | |||
|---|---|---|---|---|---|---|
| MIA vs OA | MIA vs HA | OA vs HA | ||||
| Genderª | ||||||
| Female | 17 (41.0%) | 28 (70.0%) | 6 (37.5%) | 0.018 | 1 | 0.052 |
| Male | 24 (59.0%) | 12 (30.0%) | 10 (62.5%) | |||
| Age (years)b | 58 [28-86] | 51.5 [18-84] | 59.5 [29-74] | 0.067 | 0.952 | 0.141 |
| BMI (kg/m2)b | 27 [17.9-42.3] | 24.6 [18.2-78] (n.a .= 3) | 28.25 [21.7-41] | 0.140 | 0.241 | 0.025 |
| ASAª | ||||||
| 1 | 4 (9.8%) | 1 (2.5%) | 1 (6.25%) | 0.581 | 0.446 | 0.524 |
| 2 | 19 (46.3%) | 16 (40.0%) | 5 (31.25%) | |||
| 3 | 17 (41.5%) | 22 (55.0%) | 9 (56.25) | |||
| 4 | 1 (2.4%) | 1 (2.5%) | 1 (6.25%) | |||
| Tumour sideª | ||||||
| Right | 18 (43.9%) | 18 (45.0%) | 6 (37.5%) | 1 | 0.888 | 0.831 |
| Left | 23 (56.1%) | 22 (55.0%) | 10 (62.5%) | |||
| Tumour size (mm)b | 70 [60-120] | 100 [60-260] | 85 [60-133] | <0.001 | 0.293 | 0.031 |
| Hormonal activityª | 26 (63.4%) | 23 (59.0%) (n.a .= 1) | 11 (68.75%) | 0.859 | 0.944 | 0.710 |
| Tumour entityª | ||||||
| ACC | 3 (7.3%) | 23 (57.5%) | 7 (43.75%) | <0.001 | 0.003 | 0.556 |
| ACA | 15 (36.6%) | 3 (7.5%) | 1 (6.25%) | <0.001 | 0.023 | 1 |
| MET | 3 (7.3%) | 6 (15.0%) | 3 (18.75%) | 0.482 | 0.338 | 0.700 |
| PPGL | 14 (34.1%) | 5 (12.5%) | 4 (25.0%) | 0.019 | 0.542 | 0.250 |
| CYST | 2 (4.9%) | 1 (2.5%) | 0 (0%) | 0.615 | 1 | 1 |
| Other | 4 (9.8%) | 2 (5.0%) | 1 (2.5%) | 0.432 | 1 | 1 |
| Lymph node metastasesª | 0 (0.0%) | 8 (20%) | 0 (0.0%) | 0.002 | 1 | 0.089 |
| Vascular infiltrationª | 3 (7.3%) | 16 (40%) | 6 (37.5%) | 0.016 | 0.001 | 1 |
| Infiltration of adjacent organsª | 0 (0.0%) | 4 (10%) | 1 (6.3%) | 0.054 | 0.281 | 1 |
MIA minimally invasive adrenalectomy, OA open adrenalectomy, HA hypbrid approach, BMI Body Mass Index, ASA American Association of Anesthesiologists, n.a. not available, ACC adrenocortical carcinoma, ACA adrenocortical adenoma, MET adrenal metastasis, PPGL phaeochro- mocytoma and paraganglioma, CYST adrenal cyst, ICU Intensive Care Unit
aCount (percentage)
bMedian [range]
Phaeochromocytomas and paragangliomas were more often operated via MIA (n=14, 34.1% than via OA (n=5, 12.5%); (p=0.019). Adrenal tumors operated via OA were signifi- cantly larger than those operated via MIA (median size 100 mm [range 60-260 mm] vs 70 mm [range 60-120 mm], p <0.001). There were no statistical differences in tumour size between MIA and HA, as well as between HA and OA groups. Compared with tumors operated via laparoscopic or retroperitoneoscopic approaches, those operated via OA or HA had a greater rate of infiltration into neighbouring ves- sels (n=16, 40% (p=0.016) and n=6, 37.5% (p=0.001) vs n=3, 7.5%, respectively). No differences in infiltration of adjacent organs were noted between the groups.
With respect to all other observed underlying conditions, no evidence of significantly different distributions between MIA, OA, and HA were identified. Moreover, the three groups did not differ in terms of the proportion of hormone- producing lesions or the side of the lesion.
Table 5 presents the group comparisons for the intra- and postoperative outcomes. Notably, regarding the duration of surgery, the MIA procedure lasted significantly shorter (median time 108.5 min [range 57-254 min]) than the OA and HA procedures did (median times 188 min [range 52-825] and 226.5 [range 136-466], respectively; p <0.001 for both). At the same time, significantly less multivisceral resections were performed via MIA (n=1, 2.4%) than OA (n=20, 50%) and HA (n=6, 37.5%), (p<0.001 and p=0.002, respectively).
No significant difference in the need for blood transfusion was detected among the groups. The occurrence of post- operative complications was lower in the MIA procedures than in the OA and HA procedures (p=0.003 and p=0.004, respectively). However, no differences in the rate of major
complications were found. MIA patients were less frequently transferred to the ICU than OA and HA patients (p<0.001 and p=0.028, respectively) and had shorter hospital stays (p<0.001 for both). When comparing the open and hybrid groups, no differences in patient and tumour characteristics as well as intra- or postoperative outcome parameters were demonstrated. Importantly, no patients died during the post- operative hospital stay.
ªCount (percentage)
bMedian [range]
In the study cohort, a total of 34 patients underwent surgery for adrenocortical carcinoma (ACC) measur- ing ≥ 60 mm. The characteristics of the patients are sum- marized in Table 6.
Complete resection (R0) was achieved in 27 ACC patients (79.4%), while 4 patients (11.8%) had microscopic residual disease (R1), including two operated via HA and two via OA. Additionally, 3 patients (8.8%) had an unknown resec- tion status (Rx), all of whom underwent OA.
For three patients with ACC who underwent open sur- gery, no follow-up data were available. These patients were excluded from the survival analysis. Among patients with ACC included in the survival analysis, the median follow- up time was 37 months [range: 3-154 months], and the median progression-free survival was 19 months [range: 2-154 months]. Survival analysis showed no statistically sig- nificant differences in overall survival (OS) and progression- free survival (PFS) between surgical techniques (log-rank p>0.05), as shown in Fig. 1. A pairwise comparison of OS and PFS between hybrid and open adrenalectomy showed no significant differences (p=0.31 and p=0.84, respectively).
In the univariate Cox regression analysis of the five S-GRAS score components in ACC, tumour stage (according
| MIA (n=41) | OA (n=40) | HA (n=16) | p Value | |||
|---|---|---|---|---|---|---|
| MIA vs OA | MIA vs HA | OA vs HA | ||||
| Duration of surgery (minutes)b | 108.5 [57-254] (n.a .= 1) | 188 [52-825] (n.a. = 3) | 226.5 [136-466] | <0.001 | <0.001 | 0.102 |
| Multivisceral resectionª | 1 (2.4%) | 20 (50.0%) | 6 (37.5%) | <0.001 | 0.002 | 0.582 |
| Blood transfusionª | 2 (4.9%) | 8 (20%) | 3 (18.7%) | 0.084 | 0.253 | 1 |
| ICU stayª | 16 (39%) | 33 (82.5%) | 13 (81.3%) | <0.001 | 0.010 | 1 |
| Length of postoperative ICU stay (days)b | 1 [0.5-4] | 1 [1-38] | 1 [0.5-14] | 0.237 | 0.417 | 0.903 |
| Length of postoperative hospital stay (days)b | 4 [1-13] | 10 [3-78] | 9 [4-40] | <0.001 | <0.001 | 0.519 |
| Complications (any)ª | 3 (7.3%) | 15 (37.5%) | 7 (43.7%) | 0.003 | 0.004 | 0.897 |
| Type of Complicationsª | 0.6171 | |||||
| Major | 0 (0.0%) | 3 (7.5%) | 2 (12.5%) | 0.116 | 0.0752 | |
| Minor | 3 (7.3%) | 12 (30%) | 5 (31.25%) | 0.011 | 0.032 | |
MIA minimally invasive adrenalectomy, OA open adrenalectomy, HA hybrid approach, n.a. not available, ICU Intensive Care Unit
Table 6 Patient and tumour characteristics, along with intra- and postoperative outcomes after surgery for adrenocortical carcinoma measuring ≥ 60 mm (n=34)
Patient and tumor characteristics
| Genderª | Female | 22 (64.7%) |
| Male | 12 (35.3%) | |
| Age (years)b | 55 [18-77] | |
| BMI (kg/m2)b (n.a .= 2) | 31 [23-78] | |
| ASAª | 1 | 2 (5.9%) |
| 2 | 11 (32.4%) | |
| 3 | 20 (58.8%) | |
| 4 | 1 (2.9%) | |
| Localization of the adrenal tumourª | Right | 17 (50.0%) |
| Left | 17 (50.0%) | |
| Tumour size (mm)b | 105 [65-260] | |
| Hormonal activityª (n.a .= 1) | 24 (70.6%) | |
| Ki67 | 17.5 [3-80] | |
| R-status | R0 | 27 (79.4%) |
| R1 | 4 (11.8%) | |
| Rx | 3 (8.8%) | |
| S-GRAS-Score | 1 | 4 (11.8%) |
| 2 | 3 (8.8%) | |
| 3 | 5 (14.7%) | |
| 4 | 15 (44.1%) | |
| 5 | 4 (11.8%) | |
| 7 | 2 (5.9%) | |
| 8 | 1 (2.9%) | |
| Metastases to other organs at the time of operation | 6 (17.6%) | |
| Lymph node metastasesª | 6 (17.6%) | |
| Vascular infiltration | 15 (44.1%) | |
| Infiltration of adjacent organs | 4 (11.8%) | |
| Intra- and postoperative course | ||
| Technique1 | Minimally invasive | 4 (11.8%) |
| Open surgery | 23 (67.6%) | |
| Hybrid approach | 7 (20.6%) | |
| Duration of surgery (minutes)b (n.a .= 2) | 188 [73-825] | |
| Multivisceral resectionª | Yes | 15 (44.1%) |
| Blood transfusion | Yes | 8 (23.5%) |
| ICU stayª | Yes | 26 (76.5%) |
| Length of postoperative ICU stayb | 1 [0-38] | |
| Length of postoperative hospital stayb | 12.5 [3-78] | |
| Complications (any)ª | Yes | 13 (18.1%) |
| Type of complicationsª | Minor | 10 (29.4%) |
| Major | 3 (8.8%) |
n.a. not available, ICU Intensive Care Unit aCount (percentage) bMedian [range]
to ENSAT classification) was a significant predictor of over- all survival (OS) (HR=4.66, p=0.041) and progression-free survival (PFS) (HR=2.56, p=0.004) (see Supplementary Tables 1 and 2, respectively). The Ki-67 index was signifi- cantly associated with PFS (HR = 1.03, p=0.004) but not with OS (HR =1.06, p=0.081), while tumour size, patient’s
age at surgery, and tumour resection status had no significant effect on OS or PFS of ACC patients.
As presented in Supplementary Tables 3 and 4, the uni- variate cox regression analysis of the S-GRAS score, ASA classification, and surgical technique identified S-GRAS score as predictive of OS (HR =5.79, p=0.0257 and PFS
1.00
Overall survival
0.75
0.50
MIA
- - HA
. . OA
0.25
p = 0.34
0.00
0
20
40
60
80
100
Time in weeks
(a)
(HR=2.48; p=0.0113). Both, ASA classification and the surgical method had no significant effect on overall and progression-free survival. However, wide confidence inter- vals demonstrate the model’s instability. The Ridge Regres- sion model stabilized estimates and confirmed the S-GRAS score as an independent predictor of OS (HR =6.00) and PFS (HR=1.50). ASA classification and surgical technique did not significantly impact survival outcomes. The results of the Ridge regression analysis for S-GRAS score, ASA classification, and surgical technique in relation to survival are presented in the Supplementary Tables 5 and Table 6.
Patients with the lowest S-GRAS scores (1-3) had a longer PFS than those with S-GRAS scores of 4-5 (p=0.016), but not a significantly longer OS (p=0.14). Compared to patients with an S-GRAS score of 6-8, those with the lowest S-GRAS scores showed favorable PFS (p=0.026) and OS (p=0.003). No significant difference in OS or PFS was observed between patients with S-GRAS scores of 4-5 and 6-8. A detailed analysis of the impact of the S-GRAS score on survival is presented in Supplemen- tary Fig. 1.
Discussion
This study primarily aimed to analyse the outcomes of hybrid adrenalectomy (HA) for large adrenal tumors (≥60 mm), comparing it to minimally invasive adrenalec- tomy (MIA) and open adrenalectomy (OA). MIA offered shorter operative times, reduced minor complication rates, and shorter hospital stays and was predominantly utilized for smaller and less invasive tumors. In contrast, OA and HA were more frequently performed for more aggressive tumors, including adrenocortical carcinomas (ACC), and
1.00
Progression-free survival
0.75
0.50
MIA
HA
OA
0.25
p = 0.41
0.00
0
20
40
60
80
100
Time in weeks
(b)
for cases requiring multivisceral resections. Importantly, no significant differences in intra- and postoperative outcomes were observed between OA and HA in our patients, nor did we discover significant differences in overall survival (OS) or progression-free survival (PFS) in patients with ACC treated with different surgical techniques. These findings support a tailored approach for large adrenal tumours. Pre- operative assessment and individualized surgical procedure based on tumour characteristics therefore seem possible and mandatory.
With increasing experience in minimally invasive adre- nal surgery, the indications for laparoscopic adrenalectomy have broadened [6, 8, 17-20]. Reported conversion rates vary, from none [21] to 20% [22]. In our cohort, the conver- sion rate for adrenal masses measuring ≥60 mm was 28%. Planned conversions because of inadequate anatomical over- view, adhesions to surrounding structures or infiltration of adjacent organs accounted for 15.8%, while intraoperative conversion in primarily questionable cases was indicated to prevent tumour rupture or other unnecessary complica- tions in 12.3% of cases. Contrary to the findings reported by Higashihara et al., where bleeding caused 45% of conversion [9], none of the conversions in our cohort were performed due to bleeding. The need for possible conversion should be anticipated as part of the surgical strategy for large and complex tumors.
A few studies have compared converted adrenalectomies with minimally invasive procedures in terms of intraop- erative and immediate postoperative outcomes. Schweitzer et al. reported that tumour size greater than 60 mm was associated with conversion to open surgery [23]. However, Gaujoux et al. found no association between tumour size and conversion in their cohort [13]. Notably, in their study, tumours larger than 120 mm were primarily approached via
open surgery. In addition, they identified conversion to open surgery as an independent predictive factor for medical com- plications, including pulmonary and thromboembolic events as well as organ failure, but not for surgical complications [13]. Similarly, Schweitzer et al. reported that conversion was associated with a postoperative Clavien-Dindo grade II-V morbidity in patients undergoing surgical treatment for pheochromocytoma [23]. No distinction was made between medical and surgical complications in their analysis. In our cohort, conversion was associated with a higher rate of minor complications but did not lead to an increase in major complications compared to MIA.
In line with the findings of Schweitzer et al., our patient cohort also showed a longer hospital stay following conver- sion to open adrenalectomy compared to minimally inva- sive surgery [23]. Additionally, consistent with the results of Gaujoux et al. [13] and Higashihara et al. [9], conversion in our cohort was associated with prolonged operative time. However, tumors operated via HA were more frequently malignant and demonstrated greater vascular infiltration and lymph node involvement. Thus, as possible explana- tions for the prolonged operation time, surgical complex- ity and radicality can be assumed. Given these factors, a more relevant question is whether conversion leads to worse postoperative outcomes compared to direct open surgery. More specifically, it is worth considering whether certain intra- and postoperative complications could be avoided by opting directly for open surgery rather than beginning with a minimally invasive approach while anticipating the pos- sibility of conversion. Importantly, in our patient cohort, no statistically significant differences were observed between HA and OA in this regard.
While combining laparoscopic and open approaches in one operation has been studied in pancreatic surgery [24, 25], data on the hybrid approach in adrenalectomy are scarce. The strategic use of conversion may offer a balanced approach by combining the benefits of minimally invasive techniques with the safety of open surgery in challenging cases [14]. Laparoscopy not only provides reduced postop- erative pain and shorter hospital stays [8], but also offers technical benefits in adrenal surgery given the anatomic location. The distal subdiaphragmatic region can be reached more easily via laparoscopy than via open surgery. Thus, mobilization of the spleen or liver and parts of the adrenal tumor laparoscopically may facilitate the next surgical steps conducted via the open approach. The open approach allows for easier management of vascular structures, identification of tumor infiltration and, therefore, a reduced risk of incom- plete tumour resection [26]. The potential advantage of the hybrid approach in allowing for a smaller incision compared to primary open surgery has yet to be studied.
While none of the adrenalectomies for tumors larger than 60 mm were performed via the robotic approach (RA)
during the study period at our center, the method has been increasingly applied in other centers [27], particularly in large tumors [28]. Studies suggest that RA offers advan- tages in specific clinical scenarios, including shorter opera- tive times for tumors ≥6 mm, patients with high BMI, and those with previous abdominal surgery [29, 30]. RA is also associated with shorter hospital stays [31, 32]. Interestingly, the need for conversion decreases with tumor size in RA compared to LA [33, 34]. While conversion remains safe when necessary, RA represents an increasingly preferred option for large adrenal tumors, particularly where resources and expertise are available. Importantly, while LA remains more cost-effective overall, this difference decreases with increasing tumor size, making RA comparatively more effi- cient for tumors ≥40 mm [35]. Moreover, recent institutional data suggest that RA may lead to lower overall costs due to shorter hospital stays, despite higher disposable expenses [32]. Nevertheless, access to robotic platforms remains lim- ited in many centers [28], highlighting the continued rel- evance of discussing minimally invasive, hybrid and open approaches.
Unlike the findings of Delozier et al. [10], our results showed that conversion did not negatively affect survival outcomes in ACC. Both the S-GRAS score and ENSAT clas- sification emerged as significant predictors of OS and PFS, while the choice of surgical method-whether MIA, OA, or HA-did not significantly impact survival outcomes. Thus, in our patients with ACC, survival outcomes were predomi- nantly influenced by tumour biology and stage rather than the choice of surgical technique.
Our data highlight the critical importance of careful preoperative assessment and a tailored surgical approach based on tumour characteristics and the individual patient’s clinical status. Conversion to an open approach should be considered as a strategic maneuver to optimize oncologic outcomes [3, 4], rather than being perceived as a surgical failure. Future studies should explore whether a proactive, strategy-driven approach to conversion can further improve outcomes in complex adrenal surgeries, particularly in cases of malignancy.
This study has several limitations that should be consid- ered when interpreting the results. First, it was conducted over an extended period at a single tertiary referral center for endocrine surgery, where all adrenalectomies were per- formed by highly experienced visceral surgeons. This high level of surgical expertise and the specialized setting may not reflect broader clinical practice, potentially limiting the generalizability of our findings to other institutions or surgi- cal teams with different levels of experience and resources. However, complex adrenal surgeries, especially in cases suspected of malignancy, should be referred to special- ized centers [4]. Second, adrenal tumors measuring at least 60 mm are relatively rare, resulting in a limited cohort size
with heterogeneous adrenal pathologies. Lastly, our study was retrospective in nature, and prospective studies with larger patient cohorts are needed to validate our findings and explore the impact of conversion on short-term surgical and medical, as well as long-term oncologic outcomes in cases of adrenal malignancy.
Conclusions
Our study highlights the importance of an individualized surgical approach for large adrenal tumors (≥60 mm) that considers both tumor-specific and patient-specific factors as well as the surgeon’s expertise. While minimally invasive adrenalectomy offers advantages such as shorter operative times and reduced complication rates, the use of open and hybrid approaches is justified in complex cases, particularly when addressing aggressive or large tumors. Importantly, conversion from minimally invasive to open surgery should not be regarded as a complication but rather as a strategic decision that enhances patient safety and optimizes onco- logic outcomes. Our results indicate that conversion did not significantly impact overall or progression-free survival in adrenocortical carcinoma patients. Instead, the S-GRAS score and ENSAT classification were the primary predictors of survival, underscoring the need for a robust preoperative assessment and a tailored surgical approach. Further pro- spective studies are necessary to evaluate and compare the roles of laparoscopic, hybrid, open, and robotic adrenalec- tomy in improving intraoperative safety, oncologic outcomes and cost-effectiveness in surgical management of large and complex adrenal tumors.
Supplementary Information The online version contains supplemen- tary material available at https://doi.org/10.1007/s13304-025-02388-7.
Funding Open Access funding enabled and organized by Projekt DEAL.
Data availability The datasets generated during and analyzed during the current study are not publicly available due to reasons of sensitivity and are only available from the corresponding author on reasonable request.
Open Access This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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