Genetic background and intraoperative haemodynamic instability in patients with pheochromocytoma and paraganglioma: a multicenter retrospective study.

in International journal of surgery (London, England) by Minghao Li, Jing Zhang, Yingxian Pang, Yao He, Yanting Shen, Jing Wang, Xiaowen Xu, Jiahao Liu, Kai Cheng, Zhi Li, Yujun Liu, Xin Gao, Graeme Eisenhofer, Jingjing Jiang, Longfei Liu

TLDR

  • The study looked at how well patients with certain types of tumors called pheochromocytomas and paragangliomas (PPGLs) did during surgery. They found that the genetic background of the patients was a significant factor in determining how well they did during surgery. Specifically, most patients with PPGL due to genetic mutations in the HRAS gene had intraoperative haemodynamic instability (IHI), while only half of patients with PPGL due to genetic mutations in the VHL gene had IHI. The study also found that age, tumor size, and the presence of certain symptoms were also factors in determining how well patients did during surgery.

Abstract

Perioperative management to maintain intraoperative haemodynamic stability is crucial during surgical treatment of pheochromocytomas and paragangliomas (PPGLs). Although approximately 70% of PPGLs carry pathogenic variants (PVs) in susceptibility genes, whether intraoperative haemodynamic instability (IHI) is associated with genetic background remains unclear. This study aimed to analyse IHI in patients with PPGL due to PVs in different genes. This retrospective study recruited 756 patients with abdominal PPGL from two tertiary care centres. Clinical information including sex, age, catecholamine-associated signs and symptoms (CAS), tumour location and size, biochemistry, and perioperative characteristics were collected. Genetic mutations were investigated using next-generation sequencing. Among the 671 patients included in the analysis, 61.8% (415/671) had IHI. IHI was significantly associated with genetic background in patients with PPGL. Most (80.9%, 89/110) patients with PPGL due to PVs in HRAS suffered IHI. In contrast, only half (31/62) of patients with PPGL due to PVs in VHL had IHI. In the multivariate regression analysis, compared to those with negative genetic testing results, patients with PPGL due to PVs in HRAS (OR 3.82, 95% CI 2.187-6.679, P<0.001), the other cluster 2 genes (OR 1.95, 95% CI 1.287-2. 569, P< 0.05), and cluster 1 genes other than VHL (OR 2.35, 95% CI 1.338-4.111, P<0.05) were independent risk factors for IHI, while PVs in VHL was not independent risk factor (OR 1.09, 95% CI 0.605-1.953, P>=0.05). In addition, age at diagnosis of primary tumour, presenting of CAS, and tumour size were identified as independent factors for IHI. The nomogram illustrated that genetic background as sharing the largest contribution to IHI, followed by tumour size, age, and presenting of CAS. IHI is associated with the genetic background in patients with PPGL. The perioperative management of patients with PPGL can be personalized according to their genetic backgrounds, tumour size, age, and presenting of CAS.

Overview

  • The study aims to analyze intraoperative haemodynamic instability (IHI) in patients with pheochromocytomas and paragangliomas (PPGLs) due to pathogenic variants (PVs) in different genes. The study recruited 756 patients with abdominal PPGL from two tertiary care centres. Clinical information and genetic mutations were collected. The study found that IHI was significantly associated with genetic background in patients with PPGL. Most patients with PPGL due to PVs in HRAS suffered IHI, while only half of patients with PPGL due to PVs in VHL had IHI. In the multivariate regression analysis, genetic background, tumour size, age, and presenting of CAS were independent factors for IHI. The nomogram illustrated that genetic background as sharing the largest contribution to IHI, followed by tumour size, age, and presenting of CAS.

Comparative Analysis & Findings

  • The study compared IHI under different experimental conditions or interventions in patients with PPGL due to PVs in different genes. The study found that IHI was significantly associated with genetic background in patients with PPGL. Most patients with PPGL due to PVs in HRAS suffered IHI, while only half of patients with PPGL due to PVs in VHL had IHI. In the multivariate regression analysis, genetic background, tumour size, age, and presenting of CAS were independent factors for IHI.

Implications and Future Directions

  • The study's findings suggest that perioperative management of patients with PPGL can be personalized according to their genetic backgrounds, tumour size, age, and presenting of CAS. The study highlights the importance of genetic testing in predicting IHI in patients with PPGL. Future research should focus on developing personalized perioperative management strategies based on genetic testing results and other clinical factors.
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