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Pheochromocytoma recurrence in hereditary disease: does a cortical-sparing technique increase recurrence rate?

Published:October 10, 2022DOI:https://doi.org/10.1016/j.surg.2022.05.003

      Abstract

      Background

      Posterior retroperitoneoscopic adrenalectomy is an appealing approach for patients with hereditary pheochromocytoma and lends well to cortex preservation. We sought to examine pheochromocytoma recurrence in patients with hereditary pheochromocytoma in the era of posterior retroperitoneoscopic adrenalectomy and evaluate the predictors of recurrence.

      Methods

      Patients with hereditary pheochromocytoma who underwent adrenalectomy for pheochromocytoma between 1995 and 2020 with biochemical cure and follow-up >1 year were identified. Recurrence was defined as plasma metanephrines above the upper limit of normal with radiographic evidence of disease in the ipsilateral adrenal bed.

      Results

      Seventy-eight hereditary pheochromocytoma patients (median age = 32.4 years; 60.3% women) underwent 114 adrenalectomies for pheochromocytoma. Of these patients, 40 had multiple endocrine neoplasia type 2A (51.3%), 10 had multiple endocrine neoplasia type B (12.8%), 17 had von Hippel-Lindau disease (21.8%), and 11 had neurofibromatosis type 1 (14.1%). Thirty-eight adrenalectomies (33.3%) were performed before the introduction of posterior retroperitoneoscopic adrenalectomy and 76 (66.7%) after. Cortical-sparing technique was performed in 62 (54.4%) adrenalectomies, with no difference in its use before and after posterior retroperitoneoscopic adrenalectomy introduction (P > .05). During a median follow-up of 80.7 months (interquartile range 43.4–151.2), 12 ipsilateral recurrences (10.5%) were identified. There was no difference in recurrence before and after the introduction of posterior retroperitoneoscopic adrenalectomy or by surgical technique or approach of the entire cohort (P > .05). Recurrence was more common in those with RET M918T mutation (23.5% vs 8.2%; P = .05). Patients with RET M918T mutations had a shorter recurrence-free survival (P = .013). On multivariate analysis, only RET M918T mutation was independently associated with an increased recurrence risk (hazard ratio = 4.30; 95% confidence interval, 1.26–14.66; P = .019).

      Conclusion

      The introduction of posterior retroperitoneoscopic adrenalectomy did not influence the recurrence rate after adrenalectomy for hereditary pheochromocytoma patients. Patients with a RET M918T germline mutation are at increased risk for pheochromocytoma recurrence and may benefit from initial total adrenalectomy.
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      References

        • Lenders J.W.
        • Eisenhofer G.
        • Mannelli M.
        • Pacak K.
        Phaeochromocytoma.
        Lancet. 2005; 366: 665-675
        • Fishbein L.
        • Leshchiner I.
        • Walter V.
        • et al.
        Comprehensive molecular characterization of pheochromocytoma and paraganglioma.
        Cancer Cell. 2017; 31: 181-193
        • Favier J.
        • Amar L.
        • Gimenez-Roqueplo A.P.
        Paraganglioma and phaeochromocytoma: from genetics to personalized medicine.
        Nat Rev End1ocrinol. 2015; 1: 101-111
        • Flores S.K.
        • Estrada-Zuniga C.M.
        • Thallapureddy K.
        • Armaiz-Peña G.
        • Dahia P.L.M.
        Insights into mechanisms of pheochromocytomas and paragangliomas driven by known or new genetic drivers.
        Cancers (Basel). 2021; 13: 4602
        • Wachtel H.
        • Fishbein L.
        Genetics of pheochromocytoma and paraganglioma.
        Curr Opin Endocrinol Diabetes Obes. 2021; 28: 283-290
        • Neumann H.P.H.
        • Tsoy U.
        • Bancos I.
        • et al.
        Comparison of pheochromocytoma-specific morbidity and mortality among adults with bilateral pheochromocytomas undergoing total adrenalectomy vs cortical-sparing adrenalectomy.
        JAMA Netw Open. 2019; 2e198898
        • Castinetti F.
        • Qi X.P.
        • Walz M.K.
        • et al.
        Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study.
        Lancet Oncol. 2014; 15: 648-655
        • Hahner S.
        • Spinnler C.
        • Fassnacht M.
        • et al.
        High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study.
        J Clin Endocrinol Metab. 2015; 100: 407-416
        • Lenders J.W.
        • Duh Q.Y.
        • Eisenhofer G.
        • et al.
        Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline.
        J Clin Endocrinol Metab. 2014; 99: 1915-1942
        • Lee J.E.
        • Curley S.A.
        • Gagel R.F.
        • Evans D.B.
        • Hickey R.C.
        Cortical-sparing adrenalectomy for patients with bilateral pheochromocytoma.
        Surgery. 1996; 120 (discussion 1070–1071): 1064-1070
        • Grubbs E.G.
        • Rich T.A.
        • Ng C.
        • et al.
        Long-term outcomes of surgical treatment for hereditary pheochromocytoma.
        J Am Coll Surg. 2013; 216: 280-289
        • Nagaraja V.
        • Eslick G.D.
        • Edirimanne S.
        Recurrence and functional outcomes of partial adrenalectomy: a systematic review and meta-analysis.
        Int J Surg. 2015; 16: 7-13
        • Dickson P.V.
        • Alex G.C.
        • Grubbs E.G.
        • et al.
        Posterior retroperitoneoscopic adrenalectomy is a safe and effective alternative to transabdominal laparoscopic adrenalectomy for pheochromocytoma.
        Surgery. 2011; 150: 452-458
        • Perrier N.D.
        • Kennamer D.L.
        • Bao R.
        • et al.
        Posterior retroperitoneoscopic adrenalectomy: preferred technique for removal of benign tumors and isolated metastases.
        Ann Surg. 2008; 248: 666-674
        • Andrews K.A.
        • Ascher D.B.
        • Pires D.E.V.
        • et al.
        Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD.
        J Med Genet. 2018; 55: 384-394
        • Walz M.K.
        • Peitgen K.
        • Diesing D.
        • et al.
        Partial versus total adrenalectomy by the posterior retroperitoneoscopic approach: early and long-term results of 325 consecutive procedures in primary adrenal neoplasias.
        World J Surg. 2004; 28: 1323-1329
        • Long K.L.
        • Graham P.H.
        • Grubbs E.G.
        • Lee J.E.
        • Perrier N.D.
        Intraoperative use of indocyanine green to confirm perfusion of remnant tissue in cortical-sparing retroperitoneoscopic adrenalectomy.
        Clin Surg. 2016; 1: 1-2
        • Perrier N.D.
        • Batts K.P.
        • Thompson G.B.
        • Grant C.S.
        • Plummer T.B.
        An immunohistochemical survey for neuroendocrine cells in regional pancreatic lymph nodes: a plausible explanation for primary nodal gastrinomas? Mayo Clinic Pancreatic Surgery Group.
        Surgery. 1995; 118 (discussion 965–956): 957-965
        • Gujral T.S.
        • Singh V.K.
        • Jia Z.
        • Mulligan L.M.
        Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2B.
        Cancer Res. 2006; 66: 10741-10749
        • Plaza-Menacho I.
        • Barnouin K.
        • Goodman K.
        • et al.
        Oncogenic RET kinase domain mutations perturb the autophosphorylation trajectory by enhancing substrate presentation in trans.
        Mol Cell. 2014; 53: 738-751
        • Korpershoek E.
        • Petri B.J.
        • Post E.
        • et al.
        Adrenal medullary hyperplasia is a precursor lesion for pheochromocytoma in MEN2 syndrome.
        Neoplasia. 2014; 16: 868-887