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Postoperative Management in Patients with Pheochromocytoma and Paraganglioma.

ABSTRACT: Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting neuroendocrine tumors of the adrenal medulla and sympathetic/parasympathetic ganglion cells, respectively. Excessive release of catecholamines leads to episodic symptoms and signs of PPGL, which include hypertension, headache, palpitations, and diaphoresis. Intraoperatively, large amounts of catecholamines are released into the bloodstream through handling and manipulation of the tumor(s). In contrast, there could also be an abrupt decline in catecholamine levels after tumor resection. Because of such binary manifestations of PPGL, patients may develop perplexing and substantially devastating cardiovascular complications during the perioperative period. These complications include hypertension, hypotension, arrhythmias, myocardial infarction, heart failure, and cerebrovascular accident. Other complications seen in the postoperative period include fever, hypoglycemia, cortisol deficiency, urinary retention, etc. In the interest of safe patient care, such emergencies require precise diagnosis and treatment. Surgeons, anesthesiologists, and intensivists must be aware of the clinical manifestations and complications associated with a sudden increase or decrease in catecholamine levels and should work closely together to be able to provide appropriate management to minimize morbidity and mortality associated with PPGLs.

SUBMITTER: Mamilla D

PROVIDER: S-EPMC6678461 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Postoperative Management in Patients with Pheochromocytoma and Paraganglioma.

Mamilla Divya D Araque Katherine A KA Brofferio Alessandra A Gonzales Melissa K MK Sullivan James N JN Nilubol Naris N Pacak Karel K

Cancers 20190703 7

Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting neuroendocrine tumors of the adrenal medulla and sympathetic/parasympathetic ganglion cells, respectively. Excessive release of catecholamines leads to episodic symptoms and signs of PPGL, which include hypertension, headache, palpitations, and diaphoresis. Intraoperatively, large amounts of catecholamines are released into the bloodstream through handling and manipulation of the tumor(s). In contrast, there could also ...[more]

PMID: 31277296

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Project description:BackgroundDramatic hemodynamic fluctuation occurs frequently during surgery for pheochromocytoma or paraganglioma. However, the criteria of intraoperative hemodynamic instability vary widely, and most of them were defined arbitrarily but not according to patients' prognosis. The objective was to analyze the relationship between different thresholds and durations of intraoperative hyper-/hypotension and the risk of postoperative complications in patients undergoing surgery for pheochromocytoma or paraganglioma.MethodsThis was a retrospective single-center cohort study performed in a tertiary care hospital from January 1, 2005 to December 31, 2017. Three hundred twenty-seven patients who underwent surgery for pheochromocytoma or paraganglioma, of which the diagnoses were confirmed by postoperative pathologic examination, were enrolled. Those who were less than 18?years, underwent surgery involving non-tumor organs, or had incomplete data were excluded. The primary endpoint was a composite of the occurrence of AKI or other complications during hospital stay after surgery. Multivariate Logistic regression models were used to analyze the association between different thresholds and durations of intraoperative hyper-/hypotension and the development of postoperative complications.ResultsForty three (13.1%) patients developed complications during hospital stay after surgery. After adjusting for confounding factors, intraoperative hypotension, defined as systolic blood pressure (SBP) of ?95?mmHg for ?20?min (OR 3.211; 99% CI 1.081-9.536; P =?0.006), SBP of ?90?mmHg for ?20?min (OR 3.680; 98.8% CI 1.107-12.240; P =?0.006), SBP of ?85?mmHg for ?10?min (OR 3.975; 98.3% CI 1.321-11.961; P =?0.003), and SBP of ?80?mmHg for ?1?min (OR 3.465; 95% CI 1.484-8.093; P =?0.004), were associated with an increased risk of postoperative complications. On the other hand, intraoperative hypertension was not significantly associated with the development of postoperative complications.ConclusionsFor patients undergoing surgery for pheochromocytoma or paraganglioma, intraoperative hypotension is associated with increased postoperative complications; and the harmful effects are level- and duration-dependent. The effects of intraoperative hypertension need to be studied further.

Project description:BackgroundPheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors that are mostly benign. Metastatic disease does occur in about 10% of cases of PCC and up to 25% of PGL, and for these patients no effective therapies are available. Patients with mutations in the succinate dehydrogenase subunit B (SDHB) gene tend to have metastatic disease. We hypothesized that a down-regulation in the active succinate dehydrogenase B subunit should result in notable changes in cellular metabolic profile and could present a vulnerability point for successful pharmacological targeting.MethodsMetabolomic analysis was performed on human hPheo1 cells and shRNA SDHB knockdown hPheo1 (hPheo1 SDHB KD) cells. Additional analysis of 115 human fresh frozen samples was conducted. In vitro studies using N1,N11-diethylnorspermine (DENSPM) and N1,N12- diethylspermine (DESPM) treatments were carried out. DENSPM efficacy was assessed in human cell line derived mouse xenografts.ResultsComponents of the polyamine pathway were elevated in hPheo1 SDHB KD cells compared to wild-type cells. A similar observation was noted in SDHx PCC/PGLs tissues compared to their non-mutated counterparts. Specifically, spermidine, and spermine were significantly elevated in SDHx-mutated PCC/PGLs, with a similar trend in hPheo1 SDHB KD cells. Polyamine pathway inhibitors DENSPM and DESPM effectively inhibited growth of hPheo1 cells in vitro as well in mouse xenografts.ConclusionsThis study demonstrates overactive polyamine pathway in PCC/PGL with SDHB mutations. Treatment with polyamine pathway inhibitors significantly inhibited hPheo1 cell growth and led to growth suppression in xenograft mice treated with DENSPM. These studies strongly implicate the polyamine pathway in PCC/PGL pathophysiology and provide new foundation for exploring the role for polyamine analogue inhibitors in treating metastatic PCC/PGL. PRéCIS: Cell line metabolomics on hPheo1 cells and PCC/PGL tumor tissue indicate that the polyamine pathway is activated. Polyamine inhibitors in vitro and in vivo demonstrate that polyamine inhibitors are promising for malignant PCC/PGL treatment. However, further research is warranted.

Dataset Information

Postoperative Management in Patients with Pheochromocytoma and Paraganglioma.

Publications

Postoperative Management in Patients with Pheochromocytoma and Paraganglioma.

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