Recurrent Disease in Patients With Sporadic Pheochromocytoma and Paraganglioma

Supplemental Appendix for manuscript 'Recurrent disease in patients with sporadic pheochromocytoma and paraganglioma

A nationwide study evaluating indications and outcomes for adrenalectomy in children in the Netherlands

Background: Adrenal tumors are rare in children, with neuroblastoma being most common. Surgery is the preferred treatment option, using either an open or minimally invasive approach. In this study we evaluated the incidence, spread, and perioperative outcomes of adrenalectomies in children in the Netherlands. Methods: Patients treated between 2011 and 2022 were reviewed in this nationwide study across 5 academic hospitals and the national pediatric oncology center. Patient characteristics, perioperative data, and follow-up data were collected. Results: The epidemiologic data of 187 patients and the clinical data of 137 patients were included. Annually, 18–20 adrenalectomies in children are performed, mostly for neuroblastoma (64%), pheochromocytoma (18%), and adrenocortical carcinoma (6%). Open adrenalectomy was performed in 88 patients (64%), transperitoneal laparoscopic adrenalectomy in 39 patients (29%), and posterior retroperitoneoscopic adrenalectomy in 10 patients (7%). There was a significant difference in duration of surgery between these approaches (median 171 minutes [interquartile range, 120–213], 105 minutes [interquartile range, 85–148], and 67 minutes [interquartile range, 53–101], respectively, P &lt; .001). Minimally invasive adrenalectomy was used more frequently in older patients with presumed benign disease. Perioperative complications occurred in 25 patients (18%), and 36 patients (26%) had a postoperative complication, of which 3 were major. Disease recurrence was observed in 32% of patients. Conclusion: Adrenalectomies in children are rare in the Netherlands, especially for non-neuroblastoma tumors, and most surgeons perform less than 1 procedure per year. Open adrenalectomy is usually performed for suspected malignant tumors, whereas minimally invasive approaches are used more selectively.</p

PRAP study - partial versus radical adrenalectomy in hereditary pheochromocytomas

Objective: Hereditary pheochromocytoma (hPCC) commonly develops bilaterally, causing adrenal insufficiency when standard treatment, radical adrenalectomy (RA), is performed. Partial adrenalectomy (PA) aims to preserve adrenal function, but with higher recurrence rates. This study compares outcomes of PA versus RA in hPCC. Methods: Patients with hPCC due to pathogenic variants in RET, VHL, NF1, MAX, and TMEM127 from 12 European centers (1974-2023) were studied retrospectively. Stratified analysis based on surgery type and initial presentation was conducted. The main outcomes included recurrence, adrenal insufficiency, metastasis, and mortality. Results: The study included 256 patients (223 RA, 33 PA). Ipsilateral recurrence rates were 9/223 (4%) after RA versus 5/33 (15%) after PA (P = 0.02). Metastasis and mortality did not differ between groups. Overall, 103 patients (40%) underwent bilateral adrenalectomy either synchronously or metachronously (75 RA, 28 PA). Of these, 46% developed adrenal insufficiency after PA. In total, 191 patients presented with initial unilateral disease, of whom 50 (26%) developed metachronous contralateral disease, most commonly in RET, VHL, and MAX. In patients with metachronous bilateral disease, adrenal insufficiency developed in 3/4 (75%) when PA was performed as the first operation followed by RA, compared to 1/7 (14%) when PA was performed as the second operation after prior RA (P = 0.09). Conclusion: In patients with hPCC undergoing PA, local recurrence rates are higher than after RA, but metastasis and disease-specific mortality are similar. Therefore, PA seems a safe method to preserve adrenal function in patients with hPCC, in cases of both synchronous and metachronous bilateral disease, when performed as a second operation.</p

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants:an international expert Consensus statement

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.</p

A comparison of high‑throughput plasma NMR protocols for comparative untargeted metabolomics (Metabolomics

Following publication of the original article, the authors would like to correct a sentence in the paragraph “1H-NMR spectra were recorded at 298 K…” under the heading “NMR experiments”. The sentence currently reads: “The LED pulse sequence had the form -RD-901-G1- 1801-G1-901-G2-T-901-G1-1801-G1-901-G2-t-901-acquire FID, where RD is a relaxation delay, 901 is a 901 RF pulse, G1 is the pulsed-field gradient that is applied to allow editing, 1801 is a 1801 RF pulse, G2 is a spoil gradient applied to remove unwanted magnetization components. The diffusion delay Δ is the time during which the molecules are allowed to diffuse—this is the period (901-G1-1801-G1- 901-G2-T-); and t is a delay to allow the longitudinal eddy currents caused within the sample to decay (Beckonert et al. 2007).” The sentence should read: “The LED pulse sequence had the form -RD-90°-G1- 180°-G1-90°-G2-T-90°-G1-180°-G1-90°-G2-t-90°-acquire FID, where RD is a relaxation delay, 90° is a 90° RF pulse, G1 is the pulsed-field gradient that is applied to allow editing, 180° is a 180° RF pulse, G2 is a spoil gradient applied to remove unwanted magnetization components. The diffusion delay ? is the time during which the molecules are allowed to diffuse—this is the period (90°-G1-180°-G1-90°-G2 T-); and t is a delay to allow the longitudinal eddy currents caused within the sample to decay (Beckonert et al. 2007).” This has been corrected with this erratum.</p