PARTIAL ADRENALECTOMY – HOW FAR CAN WE GO?

Abstract

Organ preservation and functional resections are the mainstays of most surgical sub-specialties at the present time. This is even more evident in endocrine surgery, where the product of secretion of these petit organs is of paramount importance. Partial adrenalectomy and cortical sparing techniques have evolved to actually compete with total adrenalectomy, the historical gold standard treatment.

Much refined imaging techniques can readily identify smaller adrenal lesions that can be addressed surgically or percutaneously given the indication. The trend towards partial adrenalectomy is straightforward in bilateral disease where steroid replacement can be avoided while for unilateral disease, normal hormonal levels can be obtained.

The reviewed publications offer deep insight into the advancement of partial or cortical sparing adrenal procedures from pioneering work to large cohort studies.

INTRODUCTION

Although laparoscopic adrenalectomy came as a great success in the early days of laparoscopic surgery, partial resections soon followed due to complex endocrine disorders needing treatment. Laparoscopic adrenal-sparing surgery has been a matter of debate amongst surgeons regarding its indications in the past decades and despite the initially favorable reports since its first employ, reported by Walz et al. in 1996 (1). While permanent adrenal insufficiency, prolonged corticoid therapy and diminished quality of life are categorical hindrances of bilateral adrenalectomy, partial adrenalectomy has not yet been universally accepted as a viable option, much less achieved gold standard level even for familial hereditary syndromes involving the adrenal glands. Moreover, the exponential development of technology, the dissemination of robotic surgery and other minimally invasive procedures have offered several different approaches to the adrenal gland with satisfactory outcomes.

This review intends to summarize these adrenal sparing techniques with their indications and outcomes in the present age of high-tech medicine.

Indications

This approach has been employed in multiple types of endocrine afflictions: Conn syndrome, Cushing’s syndromes and pheochromocytomas. As far as nonfunctioning adenomas are concerned, considering that the only indication for surgery is tumor growth or an increased dimension at the time of diagnosis, both raising the suspicion of adrenocortical carcinoma, it is implied that adrenal sparing surgery is never an option.

Initially, the cut-off value for most laparoscopic procedures was 6-7 cm, but more recent studies report that tumors larger than 4 cm may be at higher risk for malignancy (2). However, the widespread use of high-resolution imaging such as contrast-enhanced computed tomography or magnetic resonance imaging, as well as the employ of adrenal venous sampling has determined a surge in the early diagnosis of adrenal incidentalomas. Early detection leads to earlier disease diagnosis and allows for surgical ablation of the adenomas when they are smaller in size, with tumors larger than 6 cm being reported less often (3,4). Chen et al. also mention the advances in the study of hereditary syndromes as an additional screening method that aids in finding adrenal tumors while they are still in the subclinical stage, while Fu et al. indicate the use of plasma aldosterone-to-plasma renin activity as a screening tool for primary aldosteronism in hypertensive patients (3,5). All these scientific advances have had an astounding effect on both the revelation that true nonfunctioning benign adenomas are quite scarce, as well as setting the stage for a surge in the re-employment of adrenal-sparing surgery in all types of functioning adenomas.

Partial adrenalectomies should always be well planned and a multidisciplinary team that includes a surgeon with experience in endoscopic surgery (preferably endocrine surgery or urology), an endocrinologist and a radiologist should assess each case thoroughly (6). One study out of the National Cancer Center in Bethesda, Maryland, USA, required all patients considered for this parenchyma-preserving approach to have a normal ipsilateral adrenal limb or a normal contralateral gland on the preoperative CT/MRI (7). However, this cannot be seen as a universally accepted indication, seen as patients with unilateral aldosteronoma or pheochromocytoma may have bilateral tumors that are not visible even on axial imaging, therefore multiple authors advocate for the routine use of intraoperative ultrasonography to determine if there are other micronodules present, and can also be used to evaluate tumor-free margins as well as vascularization of the remaining tissue (8,9).

While maximal preservation of adrenal tissue is not paramount, several studies have found that remnant tissue volume of as low as 10-15% is sufficient to prevent postoperative hormone deficiency (10,11). This is nevertheless also a matter of debate, as most authors suggest that adequate tumor clearance signifies clear margins of at least 3-5 mm, but others prefer 10 mm margins, which might reduce the residual adrenal parenchyma and endanger the preservation of hormonal function, especially in cases where the preservation of the adrenal vein is impossible (12). Further studies regarding the proper amount of residual tissue necessary for optimal stress response are of the utmost importance, especially in patients with Cushing’s syndrome, where contralateral adrenal atrophy is almost ubiquitous (9,10).

Surgical Techniques

Laparoscopic Surgery. The most commonly used laparoscopic approach is the lateral transperitoneal approach while the retroperitoneoscopic approach is mainly used by urologists.

For the laparoscopic approach, the patient is placed in the modified semilateral position with the surgical table tilted to obtain close to 60° of elevation of the lesion side. Most setups use a 10 mm camera port 3 working ports – two 10 mm for the operating surgeon and one 5 mm for retraction.

On the right side, after achieving pneumoperitoneum using the Hasson technique, the camera port is inserted at the lateral side of the rectus abdominis, halfway between the costal margin and the umbilicus. The two ports are inserted below the costal margin, on the midclavicular line and on the anterior axillary line to obtain optimal triangulation. The last 5 mm port used for retraction is inserted either on the midline or in the subcostal area to retract the liver.

After retraction of the liver and close inspection of the subhepatic area, the parietal peritoneum and Gerota’s fascia overlaying the adrenal gland and upper pole of the kidney are incised. The gland is manipulated with extreme care using blunt instruments to avoid damage to normal adrenal tissue. The aim, as in total adrenalectomy, is to isolate the main adrenal vein but this is not necessary in peripheral tumors.

On the left side, with similar mirror work port placement, the intervention begins with takedown of the splenic flexure of the colon and medial mobilization of the spleen and pancreatic tail. Then Gerota’s fascia is incised to gain access to the adrenal gland and isolate the main adrenal vein.

For the retroperitoneoscopic approach, the patient is placed in prone position on rectangular support to obtain a close to 90° angle between the trunk and the legs. Access to the retroperitoneum is gained through a 1.5 cm incision at the level of the 12^th rib using blunt and sharp dissection with scissors. Under finger control a 5 mm port is inserted below the tip of the 11^th rib. The second 10 mm working trocar is inserted halfway between the first incision and the spine, on the horizontal line with the first working trocar. The working space is created with a blunt trocar with an inflatable balloon and dissection with the camera looking at the diaphragmatic crus. The retroperitoneum is insufflated at 20 mmHg and this aids tremendously the dissection. The mobilization of the upper pole of the kidney is the first step of the intervention. The dissection of the adrenal gland carefully starts inferiorly and medially – on the right side, the inferior vena cava will come into sight and on the left side the main adrenal vein. On the right side, the main adrenal vein will be identified after the dissection of the retrocaval arteries (13).

Using the retroperitoneoscopic approach, bilateral resections can be achieved without repositioning the patient with far less operating time than using the laparoscopic approach.

Robotic Surgery

Robotic surgery has been proven safe and feasible for adrenal surgery with certain advantages in obese patients and larger tumors, but the value of the robotic systems needs to be weighed against the financial burden for the medical system and long training process (14). The advocates of robotic surgery use the arguments of better visualization with three-dimensional depth and ergonomics during dissection, but the operating time, excluding docking time, is similar to laparoscopic surgery only after 20 procedures even for experienced laparoscopic surgeons (15). Specifically for partial adrenalectomy, the enhanced visualization and instrument articulation that allows more precise dissection can augment the ability to preserve the remnant parenchyma and its blood supply.

Regardless of the approach and technique used to approach adrenal gland when partial adrenalectomy is intended, two tantalizing questions torment the operating surgeon: Is the preservation of the main adrenal vein mandatory? And is the remnant parenchyma adequate for secretion?

Several studies have shown that the preservation of the main adrenal vein is not mandatory but may be desirable (12,16). This leaves open the way for partial resections irrespective of tumor location. If the vein had to be preserved, only patients with peripheral lesions of the adrenal gland would have been candidates for partial adrenal resections. Regarding the quality of the remnant parenchyma, the first condition for its function and practically the only that can be assessed during surgery is its blood supply. But even well vascularized remnants can fail in producing adequate amounts of hormones, this being an individual characteristic. Moreover, the medular/cortical ratio cannot be fully assessed during surgery. Although initially one third of the normal adrenal gland was stated to be required for adequate adrenocortical stress capacity, it has been demonstrated that 10-15% of residual adrenal tissue offers intact stress capacity (10).

Indocyanine green (ICG) is a non-toxic dye that can help identify vascular structures and parenchymal tissue in real time. When the dye is injected intravenously, it bounds to plasma proteins and remains confined to the intravascular space and when excited by near infrared light exhibits fluorescence. Thus, it provides real time information based on its flow through the tissues. Endocrine glands have a dense blood supply and are suited for the use of ICG, the adrenal gland having a 1.87 mL/g/min blood flow (17). When used, the ICG study resembles a CT contrast study: the adrenal arterial anatomy is first demonstrated, then the parenchyma and finally, the vein. Adrenal tumors concentrate more ICG than the normal parenchyma and are readily visible as hyperfluorescent aiding more accurate and secure transection lines and lastly after resection, the blood supply of the remnant can be evaluated (18,19). Even more, different adrenal tumors exhibit different patterns of ICG fluorescence based on their histological origin (20). By contrast, using laparoscopic ultrasound for tumor location has the limitations of interrupting the dissection maneuvers during imaging assessment.

Other Ablation Techniques

Cryoablation

Without being a routinely used procedure, the cryoprobe can be delivered either by a laparoscopic approach or percutaneously. With the probe inserted interstitially in the nodule, tissue freezing for up to -50°C is achieved via Argon gas for 10-15 minutes. The procedure is still in its infancy, and the percutaneous approach is limited to patients with severe comorbidities or metastatic adrenal nodules (21,22). Intraprocedural hypertensive crisis appears to be main concern of this intervention while complete ablation of the nodule should be demonstrated only during postprocedural hormonal workup.

Radiofrequency Ablation

Percutaneous radiofrequency ablation is effective for the treatment of benign adrenal masses in patients that are poor candidates for surgery. The patients need preoperative blockade for 2 to 3 weeks prior to the intervention. With the patient under general anesthesia, the radiofrequency probe is inserted under CT guidance. The ions around the uninsulated electrode tip vibrate producing heat that leads to cell protein denaturation (23,24).

Embolization

While the main indication for embolization remains control of retroperitoneal hemorrhage, successful embolization has been reported in patients with secreting adenomas not suitable for surgery. After super selective adrenal arteries catheterization, and identification of the main feeding vessel of the adenoma, ethanol and lipidol are used for embolization; during embolization the main adrenal vein is aspired to protect against hormone release and subsequent hypertensive crisis (25).

Outcomes

Comparative outcomes of total and partial adrenalectomies have been the subject of several studies, both for independent endocrine syndromes and overall results (2,5,26–28). However, most of these were conducted retrospectively and the patient sample was rarely above 100, with the largest group of patients included in a single study being conducted by Walz et al. in 2004, on 325 consecutive patients (2). The most recent meta-analysis, published in 2021, regarding aldosterone-producing adenomas, found only two randomized controlled trials and five non-randomized controlled trials that compared the two procedures and reported on their long-term outcomes. This is yet another fault in the existing reported results, as earlier articles had a limited follow-up period, which more recent discoveries have deemed insufficient, as metachronous development of adenomas on the contralateral adrenal gland following organ-sparing procedures can develop as late as 14 years after the initial surgery (8).

Nevertheless, results reported so far have shown favorable outcomes after partial adrenalectomy across the board. Most articles and reviews demonstrate on-par outcomes regarding operative time, blood loss, hospital stay, morbidity and local tumor control, as well as clinical outcome regarding the primary endocrine disease at follow-up. Some authors even reported a higher cure rate and shorter operative time for Conn syndrome after partial adrenalectomy (5,8,27). Postoperative steroid replacement therapy was withing acceptable ranges for patients undergoing organ-sparing surgery compared to total adrenalectomy (below 15% in most studies) and recurrence rate was 3-8% (4,29). One article published in 1996 reported a recurrence rate of 21%, but the patient sample was only 15 patients, and they were all diagnosed with hereditary syndromes (MEN 2A, MEN 2B, Von Hippel Lindau) and arguably the scientific advances in the last decade and broad use of intraoperative ultrasound, ICG and high-resolution imaging have greatly improved these outcomes (30).

In conclusion, partial adrenalectomy can be successfully employed for hereditary pheochromocytoma, Conn’s syndrome and Cushing’s syndrome through all types of minimally invasive procedures including transperitoneal, single-port and retroperitoneoscopic approaches, as well as through non-surgical procedures such as cryoablation, embolization and radiofrequency ablation. Controversial topics remain, mainly regarding the necessary volume of residual tissue, ligation of the adrenal vein, functional outcome and long-term efficacy require prospective studies on larger samples of patients.

Conflict of interest

The authors declare that they have no conflict of interest.