Transperitoneal laparoscopic surgery in large adrenal masses
Nuri Alper Sahbaz1, Ahmet Cem Dural1, Cevher Akarsu1, Deniz Guzey1, Mehmet Kulus1, Sema Ciftci Dogansen2, Meral Mert2, Halil Alis3
1Department of Surgery, Faculty of Medicine, University of Health Sciences, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
2Department of Endocrinology, Faculty of Medicine, University of Health Sciences, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
3Department of Surgery, Faculty of Medicine, Aydin University, VM Medical Park Florya Hospital, Istanbul, Turkey
Videosurgery Miniinv 2020; 15 (1): 106-111
DOI: https://doi.org/10.5114/wiitm.2019.85177
Abstract
Introduction: The laparoscopic adrenalectomy (LA) has become the gold standard since the transperitoneal laparo- scopic approach was first reported.
Aim: To evaluate the applicability, safety and short-term results of laparoscopic surgery in adrenal masses over 6 cm. Material and methods: Demographic data, hormonal activities, imaging modalities, operative findings, operation time, conversion rates, complications, duration of hospital stay and histopathologic results of 128 patients who underwent laparoscopic adrenalectomy were evaluated retrospectively. Patients included in the learning curve (n = 23), robotic surgery cases (n = 15) and patients with suspected metastasis (n = 4) were excluded from the study. Six cm mass size was taken as a reference and two groups were formed (group 1: < 6 cm, group 2: ≥ 6 cm). The results of the two groups were compared.
Results: There were 64 cases in group 1 and 22 cases in group 2. Functional mass ratio and mass sides were similar between the groups (p = 0.30 and p = 0.17, respectively). The mean mass size in group 1 was 36.4 +11.2 mm and in group 2 82.4 +15.5 mm. The conversion rate was similar between the two groups (p = 0.18). The duration of surgery was 135.5 ±8.29 min in group 1, 177.0 ±14.9 min in group 2 (p = 0.014). Morbidity and lengths of hospital stay were similar (p = 0.76, p = 0.34 respectively). Adrenocortical carcinoma was detected in three cases in group 1, which were completed laparoscopically, and in two cases in group 2, which were converted to open surgery (p = 0.46).
Conclusions: Although open surgery is still recommended in the guidelines, studies are now being carried out to ensure that laparoscopy can be safely performed on masses over 6 cm. There was no difference between short-term follow-up and histopathologic results in our study.
Key words: large adrenal tumors, adrenalectomy, laparoscopy, minimally invasive adrenalectomy.
Introduction
The laparoscopic adrenalectomy (LA) has become the gold standard since the transperitoneal laparo- scopic approach was first described by Gagner et al. [1-3]. It has been shown to demonstrate benefits in terms of safety, recovery, analgesic requirements and
hospital stay when compared to the open procedure [4, 5]. Beside these benefits, the widespread adop- tion of Laparoscopic adrenalectomy has also been due to the improvements in laparoscopic equipment and technical expertise [6].
The prevalence of adrenal incidentalomas in imaging modalities performed for different rea-
Address for correspondence
Nuri Alper Sahbaz, Department of Surgery, Faculty of Medicine, University of Health Sciences, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Tevfik Sağlam Cad. No. 11, 34147 Istanbul, Turkey, phone: +90 5055572762, e-mail: alpersahbaz@yahoo.com
sons ranges between 3% and 5% [7, 8]. Laparo- scopic adrenalectomy is considered the choice of treatment for benign small adrenal tumors and current guidelines recommend surgical removal of adrenal lesions larger than 4 cm. In contrast, adrenocortical cancer (ACC) is an uncommon malignancy, with an incidence of 0.5-2/1 million population/year. In the lack of local invasion or metastatic disease, the suspicion of ACC is solely based on the size and the imaging features of the lesion [9].
While it has been shown that tumor size is typ- ically an indicator of malignant disease, and it is unclear if the laparoscopic approach to a large and possibly malignant lesion is suitable due to concern over capsular disruption, incomplete resection, and local recurrence [10], it is still debated whether size of the tumor should be a contraindication to the lap- aroscopic adrenalectomy [11].
Malignancy being the single contraindication for LA [12, 13], the correct surgical approach depends on the ability to differentiate benign and malignant lesions, preoperatively. Without evidence of invasion to surrounding tissues, lymphadenopathy or distant metastasis, malignancy of a large adrenal tumor is difficult to identify before or maybe even during the operation [14].
During the last decade, cut-off values for ma- lignancy potential of adrenal lesions have been increased during the years in various guidelines. The more recent guidelines set this threshold as 6 cm and reported that lesions greater than 6 cm have a significant increase in risk for malignancy [15-18]. However, currently, the indication for LA for lesions > 6 cm is still a matter of debate. Some surgeons regard large tumors as a contraindica- tion [19-21] and some report series with larger adrenal tumors successfully treated laparoscopi- cally [22-24].
Aim
Our aim was to evaluate the applicability, safety and short-term results of laparoscopic surgery in ad- renal masses over 6 cm.
Material and methods
The records of 128 consecutive patients who underwent laparoscopic adrenalectomy at our in- stitution between December 2012 and December 2017 were evaluated retrospectively. Demograph- ic data, preoperative hormonal activities, imaging modalities, surgical and medical history, operative findings, operation time, conversion to open surgery, complications, duration of hospital stay and histo- pathologic results were analyzed. Patients included in the learning curve (n = 23), robotic surgery cas- es (n = 15) and patients with suspected metastasis (n = 4) were excluded from the study to reduce po- tential sources of bias. Six cm mass size was taken as a reference and two groups were formed (group 1: < 6 cm (n = 64), group 2: ≥ 6 cm (n = 22)). The results of the two groups were compared (Figure 1).
All cases were discussed in the multidisciplinary adrenal tumor board for the surgical indication. All procedures were performed by surgeons who have experience in the field of endocrine surgery and minimally invasive surgery as well.
Surgical technique
Laparoscopic adrenalectomy was performed us- ing the lateral transabdominal approach as described by Gagner et al. [1]. During the procedure we aimed at minimal handling of the tumor and resection with its surrounding fat. Energy devices (LigaSure) were used for the dissection of the tumor but all adre- nal veins were clipped before division. Metallic clips (LIGACLIP, Ethicon US, LLC) or Hem-o-lock clips (Tele- flex Medical, Research Triangle Park, NC) were used
Patients who underwent minimally invasive adrenalectomy (n = 128)
Excluded from study (n = 42)
· Learning curve period (n = 23)
· Robotic surgery (n = 15)
Patients included in the study (n = 86)
· Suspected malignancy/metastasis (n = 4)
Group 1 (< 6 cm) (n = 64)
Group 2 (≥ 6 cm) (n = 22)
A
B
C
D
for ligation. All tumors were removed using endo- scopic retrieval bags. In case of suspicion for a locally invasive tumor, the procedure was converted to open surgery for en-bloc resection ± lymph node dissec- tion according to oncological principles (Photo 1).
Ethics
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional ethics commit- tee (Registration No: 2015-161-14-11) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants includ- ed in the study.
Statistical analysis
For statistical analysis, a statistical software package (IMP version 10.0.0, SAS, Cary, NC) was used. Continuous variables were expressed as mean + SD or median and interquartile ranges. Categori-
cal variables were expressed as frequencies and percentages. Comparison of parametric continuous variables was performed using Student’s t test. The Mann-Whitney U test was used for comparison of non-parametric variables. The x2 test was used in the comparison of categorical variables. P-values of 0.05 or less were considered as statistically significant.
Results
A total of 86 patients were included in the study. Thirty-six of them were hormonally active. Demo- graphic data of the groups are given in Table I. The only difference was a female predominance in group 1.
The mean operative time was significantly lon- ger in group 2. Average blood loss, conversion rates and intra-operative complication rates did not differ between the two groups. In group 1, 3 patients re- quired conversion to an open approach. The reasons were technical difficulties in dissection in 1 case, ad- hesions due to previous surgery in the other case and renal vein injury in the last one. In group 2, also 3 patients needed conversion, two of them due to suspicion of malignancy and local invasion and one due to adhesions (Table II).
We encountered one port site hernia in group 1 and one wound infection in group 2 as a post-oper- ative complication. We did not have any mortality. Length of hospital stay was similar in both groups. Post-operative pathology results revealed 3 ACCs in group 1 and 2 ACCs in group 2 (p = 0.46) (Table III).
Discussion
Adrenalectomies have become more frequent worldwide, especially as minimally invasive tech-
| Demographics | Group 1 (< 6 cm) (n = 64) | Group 2 (≥ 6 cm) (n = 22) | P-value |
|---|---|---|---|
| Age, median (IQR) [years] | 53 (27-76) | 47 (19-79) | 0.07 |
| Gender, n (M/F) | 14/50 | 10/12 | 0.03 |
| BMI, mean ± SD [kg/m2] | 29.9 ±6.8 | 27.8 ±6 | 0.36 |
| Mass size*, mean + SD [mm] | 36.4 ±11.2 | 82.4 +15.5 | < 0.001 |
| Mass side, n (R/L) | 33/31 | 15/7 | 0.17 |
| Hormonal activity, n (non-functioning/functioning) | 38/26 | 12/10 | 0.30 |
| Imaging studies ** , n (MRI/other) | 61/3 | 18/4 | 0.06 |
IQR - interquantile range, BMI - body mass index, SD - standard deviation, *Mass size on preoperative imaging, MRI - magnetic resonanace imaging, ** other - computed tomography, scintigraphy or positron emission tomography.
| Pre-operative parameters | Group 1 (< 6 cm) (n = 64) | Group 2 (≥ 6 cm) (n = 22) | P-value |
|---|---|---|---|
| Duration of operation, mean ± SD | 135.5 ±66.3 | 177.1 ±69.9 | 0.01 |
| Estimated blood loss, median (IQR) [ml] | 50 (10-300) | 80 (25-150) | 0.23 |
| Conversion to open surgery, n (%): | 3/4.7 | 3/13.6 | 0.18 |
| Suspicion of malignancy-local invasion | 2 | ||
| Difficult dissection | 1 | ||
| Adhesion | 1 | 1 | |
| Bleeding due to vascular injury | 1 | ||
| Intra-operative complication, n (%) | 2/3.1 | 1/4.5 | 0.76 |
| Organ injury (pancreas)* | 1 | ||
| Bleeding due to vascular injury | 1 | ||
| Bleeding due to organ injury (Adrenal itself)* | 1 |
IQR - interquantile range, *no conversion required, conservative management for pancreas injury.
| Post-operative parameters | Group 1 (< 6 cm) (n = 64) | Group 2 (≥ 6 cm) (n = 22) | P-value |
|---|---|---|---|
| LOS, median (IQR) | 3 (1-9) | 3 (1-14) | 0.07 |
| Rate of ACC, n (%) | 3 (4.7) | 2 (9) | 0.46 |
| Post-operative complication, n (%): | 1 (15) | 1 (4.5) | 0.45 |
| Port site hernia | 1 | ||
| Wound infection | 1 | ||
| 30-day periooperative mortality | – | – | NA |
| Follow-up, mean + SD [months] | 36.6 ±13.5 | 34.4 ±15.4 | 0.53 |
LOS - length of hospital stay, ACC - adrenocortical carcinoma.
niques and surgical skills have improved in the last decades [25]. The size of the tumor, however, has always been a setback for a minimally invasive ap- proach as the risk of malignancy increases with size. During the last decade, cut-off values for malignan- cy potential of adrenal lesions have been increased during the years in various guidelines. The more re- cent guidelines set this threshold as 6 cm and re- ported that lesions greater than 6 cm have a signifi- cant increase in risk for malignancy. However, many adrenal adenomas are larger than 6 cm. If size is the sole criterion on which the operative approach is based, many patients with benign large adrenal tumors will have an unnecessary open adrenalecto- my that might increase their morbidity [26]. Howev- er, LA for lesions > 6 cm is still a matter of debate.
Some surgeons regard large tumors as a contrain- dication [19-21] and some report series with larger adrenal tumors successfully treated laparoscopically [22-24].
Our study confirmed the applicability and safety of laparoscopic adrenalectomy for large tumors over 6 cm by comparing operative times, conversion and complication rates, mean blood loss and hospital stay. In our study, we defined the cut-off value for large tumors as 6 cm and based our measurements on the final histopathological results, since imaging scans tend to underestimate actual size by up to 20% [27].
Laparoscopic dissection of large adrenal tumors is more demanding due to the limited space to per- form an extensive dissection. It may cause increased intra-operative blood loss, conversion rates to open
approach, mean operative time and longer hospital stay, when compared to small tumors [28]. Tiberio et al. reported in their recent work that longer hos- pital stays were associated with duration of the op- erations. In their series, they found that tumor size was not associated with longer operative times or hospital LOS [29]. Pisarska et al. also found in their large series that the size of the tumor did not af- fect the LOS [30]. In our study mean operation time for lesions ≥ 6 cm was 177 min, which was signifi- cantly longer than for smaller lesions (p = 0.01). But this longer duration of operation did not affect the length of hospital stay (p = 0.07). In their series of adrenal cysts, Pogorzelski et al. reported using the laparoscopic approach in cysts up to 13 cm and did not report any problems due to the size of the le- sions. They recommend a transperitoneal laparo- scopic approach, particularly for cysts larger than 10 cm, as this approach provides a better view of the surgical field [31].
In a large cohort of Castillo et al. (n = 227), they determined similar rates of conversions to an open approach and complications between large and small tumors. But they also reported increased op- erative time, intra-operative blood loss, and hospital LOS with large lesions [32]. Toutounchi et al., in their series, evaluated patients undergoing lateral laparo- scopic adrenalectomy with previous abdominal sur- gery, and reported that the size of the tumor was a reason for conversion [33]. In our series, intraoper- ative blood loss, rate of conversion and hospital stay were similar between groups (p = 0.23, p = 0.18 and p = 0.07 respectively). Also, the rate of complications in large tumors was not high as opposed to small masses (p = 0.76). In a recent cohort of Feo et al. (n = 200) the size of the tumor did not affect the clin- ical outcome. Likewise, duration of operation, rate of conversion, hospital LOS and complication rates were not affected by tumor size [34].
The inconsistency in the literature could be be- cause of the different definitions used to define tu- mor size regarding the guidelines, which affect the current endocrine practice [26, 35].
Hormonal activity of the lesions and body mass index (BMI) of the patients have also been shown to correlate with the operating time [26]. But contrary to the literature, in our series, hormonal activity (p = 0.30) of the tumor or the BMI of the patient (p = 0.36) does not seem to affect overall outcome of the patients.
The ACC is a very rare tumor compared to be- nign adrenal lesions [35]. According to the National Institute of Health (NIH) consensus statement, inci- dence of ACC is 25% in lesions larger than 60 mm [36]. Asari et al. also reported that 81.1% of tumors larger than 60 mm in their series were actually be- nign in the final histopathology [11]. The rate of ACC seen in both groups also did not differ in our series (p = 0.46). However, as a limitation, the retrospec- tive nature of our study and low number of patients (n = 22) with larger tumors in our series makes in- terpretation of these data less reliable. Yet, it seems to suggest that tumor size itself should not be a con- traindication for laparoscopic adrenalectomy.
Conclusions
Although open surgery is still recommended in the guidelines, studies are now being carried out to ensure that laparoscopy can be safely performed on masses over 6 cm. The results of this study support the management trends for large adrenal tumors ac- cording to recent literature. There was no difference between short-term follow-up and histopathology results in our study. Oncologic principles were not compromised in our study. In the presence of clini- cal suspicion of local invasion laparoscopy was not insisted on and there was no hesitation over conver- sion to an open approach.
Conflict of interest
The authors declare no conflict of interest.
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Received: 5.03.2019, accepted: 19.04.2019.