Adrenal fast-track and enhanced recovery in retroperitoneoscopic surgery for primary aldosteronism improving patient outcome and efficiency.

PURPOSE: No data exist on perioperative strategies for enhancing recovery after posterior retroperitoneoscopic adrenalectomy (PRA). Our objective was to determine whether a multimodality adrenal fast-track and enhanced recovery (AFTER) protocol for PRA can reduce recovery time, improve patient satisfaction and maintain safety. METHODS: Thirty primary aldosteronism patients were included. Fifteen patients were treated with 'standard-of-care' PRA and compared with 15 in the AFTER protocol. The AFTER protocol contains: a preoperative information video, postoperative oral analgesics, early postoperative mobilisation and enteral feeding, and blood pressure monitoring at home. The primary outcome was recovery time. Secondary outcomes were length of hospital stay, postoperative pain and analgesics requirements, patient satisfaction, perioperative complications and quality of life (QoL). RESULTS: Recovery time was much shorter in both groups than anticipated and was not significantly different (median 28 days). Postoperative length of hospital stay was significantly reduced in AFTER patients (mean 32 vs 42 h, CI 95%, p = 0.004). No significant differences were seen in pain, but less analgesics were used in the AFTER group. Satisfaction improved amongst AFTER patients for time of admission and postoperative visit to the outpatient clinic. There were no significant differences in complication rates or QoL. CONCLUSION: Despite no difference in recovery time between the two groups, probably due to small sample size, the AFTER protocol led to shorter hospital stays and less analgesic use after surgery, whilst maintaining and even enhancing patient satisfaction for several aspects of perioperative care. Complication rates and QoL are comparable to standard-of-care.

Changes of the CYP11B2 Expressing Zona Glomerulosa in Human Adrenals From Birth to 40 Years of Age.

BACKGROUND: Aldosterone synthase (CYP11B2) antibodies for immunohistochemistry, enables to visualize aldosterone-producing zona glomerulosa (ZG), aldosterone-producing micronodules, and aldosterone-producing adenomas. The architecture of the ZG differs in old versus young age but the evolution of the changes is not well known. The pathogenesis of aldosterone-producing micronodules and aldosterone-producing adenomas is still unclear and research on the ZG in young populations is limited. In this study, we elucidate changes in human ZG with age by quantifying the CYP11B2 expression. METHODS: We collected 83 human adrenal glands from 57 autopsy cases aged 0 to 40 years old. In 26 cases, both adrenals were available. We performed immunohistochemistry targeting CYP11B2 and quantified the relative CYP11B2 expressing area, CYP11B2 continuity, the mean gap length between CYP11B2-expressing areas and the maximum extension of CYP11B2 area (depth). RESULTS: We found a negative correlation between age and the relative CYP11B2 expressing area, a negative correlation between age and CYP11B2 continuity, a positive correlation between age and mean gap length, and a positive correlation between age and maximum CYP11B2 depth. The changes in expression patterns of relative CYP11B2 expressing area, CYP11B2 continuity and mean gap length were seen in both adrenals of the same autopsy case. CONCLUSIONS: The decline of relative CYP11B2 expressing ZG area and continuity may indicate involution of the ZG, which is supported by an increase of gaps and maximum CYP11B2 depth indicating clustering, comparable to formation of aldosterone-producing micronodules. The similarities in both adrenals from the same case indicate that these changes occur bilaterally.

CXCR4-directed [68Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS).

INTRODUCTION: Primary aldosteronism (PA) is the most common form of secondary hypertension. It is caused by overproduction of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction is crucial, because PA is cured by adrenalectomy in APA and is treated by mineralocorticoid receptor antagonists in BAH. The distinction is currently made by adrenal vein sampling (AVS). AVS is a costly, invasive and complex technical procedure with limited availability and is not superior in terms of outcomes to CT scan-based diagnosis. Thus, there is a need for a cheaper, non-invasive and readily available diagnostic tool in PA. We propose a new diagnostic imaging modality employing the positron emission tomography (PET) tracer [68Ga]Ga-PentixaFor. This tracer has high focal uptake in APAs, whereas low uptake was shown in patients with normal adrenals. Thus, [68Ga]Ga-PentixaFor PET/CT is an imaging modality with the potential to improve subtyping of PA. It is readily available, safe and, as an out-patient procedure, much cheaper diagnostic method than AVS. METHODS AND ANALYSIS: We present a two-step randomised controlled trial (RCT) protocol in which we assess the accuracy of [68Ga]Ga-PentixaFor PET/CT in the first step and compare [68Ga]Ga-PentixaFor PET/CT to AVS in the second step. In the first step, the concordance will be determined between [68Ga]Ga-PentixaFor PET/CT and AVS and a concordance probability is calculated with a Bayesian prediction model. In the second step, we will compare [68Ga]Ga-PentixaFor PET/CT and AVS for clinical outcome and intensity of hypertensive drug use defined as daily defined doses in a RCT. ETHICS AND DISSEMINATION: Ethics approval was acquired from the medical ethical committee East-Netherlands (METC Oost-Nederland). Results will be disseminated through peer-reviewed articles. TRIAL REGISTRATION NUMBER: NL9625.

Predicting surgical outcome in posterior retroperitoneoscopic adrenalectomy with the aid of a preoperative nomogram.

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy (PRA) has several advantages over transperitoneal laparoscopic adrenalectomy (TLA) regarding operative time, blood loss, postoperative pain, and recovery. However, it can be a technically challenging procedure. To improve patient selection for PRA, we developed a preoperative nomogram to predict operative time. METHODS: All consecutive patients with tumors of ≤ 7 cm and a body mass index (BMI) of < 35 kg/m2 undergoing unilateral PRA between February 2011 and March 2020 were included in the study. The primary outcome was operative time as surrogate endpoint for surgical complexity. Using ten patient variables, an optimal prediction model was created, with a best subsets regression analysis to find the best one-variable up to the best seven-variable model. RESULTS: In total 215 patients were included, with a mean age of 52 years and mean tumor size of 2.4 cm. After best subsets regression analysis, a four-variable nomogram was selected and calibrated. This model included sex, pheochromocytoma, BMI, and perinephric fat, which were all individually significant predictors. This model showed an ideal balance between predictive power and applicability, with an R2 of 38.6. CONCLUSIONS: A four-variable nomogram was developed to predict operative time in PRA, which can aid the surgeon to preoperatively identify suitable patients for PRA. If the nomogram predicts longer operative time and therefore a more complex operation, TLA should be considered as an alternative approach since it provides a larger working space. Also, the nomogram can be used for training purposes to select patients with favorable characteristics when learning this surgical approach.

Partial Adrenalectomy Carries a Considerable Risk of Incomplete Cure in Primary Aldosteronism.

PURPOSE: Laparoscopic adrenalectomy is standard treatment for patients with unilateral aldosterone-producing adenomas, but surgeons are increasingly tempted to perform partial adrenalectomy, disregarding potential multinodularity of the adrenal. We assess the diagnostic value of endoscopic ultrasound for differentiating solitary adenomas from multinodularity by examining in-depth adrenal pathology with ex vivo 11.7 T magnetic resonance imaging and immunohistochemistry. MATERIALS AND METHODS: In 15 primary aldosteronism patients, we performed intraoperative endoscopic ultrasound, ex vivo magnetic resonance imaging and histopathological examination. Every adrenal was intraoperatively and postoperatively assessed for solitary adenomas or multinodular hyperplasia. After unblinding for ex vivo magnetic resonance imaging results a second detailed histopathological examination, including immunohistochemistry analysis with CYP11B2 (aldosterone synthase) and chemokine receptor 4 (CXCR4), a new marker for aldosterone-producing adenomas, was performed. Finally, presence of somatic mutations linked to aldosterone-producing adenomas was assessed. RESULTS: The sensitivity and specificity of endoscopic ultrasound to identify multinodularity were 46% and 50%, respectively. We found multinodular hyperplasia in 87% of adrenals with ex vivo magnetic resonance imaging combined with detailed histopathology, and 6 adrenals contained multiple CYP11B2-producing nodules. Every CYP11B2 positive nodule and 61% of CYP11B2 negative nodules showed CXCR4 staining. Finally, in 4 adrenals (27%) we found somatic mutations. In multinodular glands, only 1 nodule harbored this mutation. CONCLUSIONS: Intraoperative endoscopic ultrasound in primary aldosteronism patients has low accuracy to identify multinodularity. Ex vivo magnetic resonance imaging can serve as a tool to direct detailed histopathological examination, which frequently shows CYP11B2 production in multiple nodules. Therefore, partial adrenalectomy is inappropriate in primary aldosteronism as multiple aldosterone-producing nodules easily stay behind.