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Annals of Surgical Oncology Jun 2017Pheochromocytoma and paraganglioma (PPGL) are rare neoplasms; about 10% are malignant. Literature regarding possible benefit from resection is extremely limited.
INTRODUCTION
Pheochromocytoma and paraganglioma (PPGL) are rare neoplasms; about 10% are malignant. Literature regarding possible benefit from resection is extremely limited.
METHODS
A 20 year review of all patients undergoing surgery for malignant PPGL at the Mayo Clinic Rochester Campus between 1994 and June 2014 was performed.
RESULTS
We identified 34 patients undergoing surgery for malignant PPGL. Median follow up was 6 and 5 years survival was 90% (median 11 years). Complete resection (R0) was achieved in 14 patients (41%). Median disease-free survival was 4.6 years for patients with R0 resection (up to 12 years). Only eight patients (23%) were disease-free on last follow up. Elevated preoperative fractionated metanephrines or catecholamines were documented in 23 patients (68%); these normalized in 13 of 23 patients (56%) postoperatively-with symptom relief in 15 of 18 preoperatively symptomatic patients (79%). Among 23 patients with hormone-producing tumors, significant reduction in number of antihypertensive medications was also noted postoperatively; 11 patients have remained off all antihypertensives, 6 required 1 medication, 1 required 2, while 5 required full blockade with phenoxybenzamine and a beta-adrenergic blocker.
CONCLUSION
Surgery plays a significant role in the management of selected malignant PPGL. Resection can be effective in normalizing or significantly reducing levels of catecholamines and metanephrines, and can improve hormone-related symptoms and hypertension. Surgical resection, either complete or incomplete, is associated with durable survival despite a high rate of tumor recurrence.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Female; Follow-Up Studies; Humans; Male; Middle Aged; Paraganglioma; Pheochromocytoma; Prognosis; Retrospective Studies; Survival Rate; Young Adult
PubMed: 28058556
DOI: 10.1245/s10434-016-5739-5 -
Endocrine Connections Nov 2017Preoperative preparation for adrenalectomy for pheochromocytomas and paragangliomas (PPGL) is universally recognized as necessary, while the optimal strategy remains...
PURPOSE
Preoperative preparation for adrenalectomy for pheochromocytomas and paragangliomas (PPGL) is universally recognized as necessary, while the optimal strategy remains controversial. Our aims were to increase intraoperative hemodynamic stability, expedite postoperative recovery, decrease side effects and reduce costs for patients with PPGL undergoing adrenalectomy.
METHODS
We identified 526 patients undergoing open adrenalectomy for PPGL in the West China Hospital of Sichuan University between May, 2007 and December, 2016. 149 patients received preoperative selective α-blockade with phenoxybenzamine, and 377 patients received non-selective α-blockade with prazosin, doxazosin or terazosin. There were no statistical differences between groups regarding preoperative patient and tumor characteristics. Operations were planned once hypertensive patients were well-controlled with blood pressure ≤130/85 mmHg. Intraoperatively, all patients received arterial blood pressure monitoring, and indwelling urinary catheters to record urine output. We recorded intraoperative hemodynamics, status in the postanesthesia or intensive care unit, postoperative recovery and complications.
RESULTS
Patients in the non-selective group showed a more significant decline in postoperative systolic blood pressure than the selective group ( = 0.041). Also, patients in the non-selective group appeared to receive a long-term anti-hypertensive effect, especially for diastolic blood pressure ( = 0.037), which was a novel finding, based on the current literature.
CONCLUSIONS
Our results confirmed that non-selective α-blockade produced a more significant anti-hypertensive effect than selective α-blockade. However, we found no significant difference in intraoperative hemodynamic instability, postoperative recovery and postoperative complications between groups.
PubMed: 28986400
DOI: 10.1530/EC-17-0232 -
JCEM Case Reports May 2023Pheochromocytomas are neuroendocrine tumors that arise from chromaffin cells in the adrenal medulla. Giant pheochromocytomas commonly measure greater than 7 to 10 cm,...
Pheochromocytomas are neuroendocrine tumors that arise from chromaffin cells in the adrenal medulla. Giant pheochromocytomas commonly measure greater than 7 to 10 cm, and their incidence and presentation is not well known. We present a case of a 62-year-old female with a giant 15.9 cm cystic pheochromocytoma. The patient was medically managed with oral phenoxybenzamine solution dose 4 times greater than average and was treated with a radical left nephrectomy and adrenalectomy. This case offers insight into the clinical presentation of giant pheochromocytomas and the unique challenges they present both medically and surgically.
PubMed: 37908578
DOI: 10.1210/jcemcr/luad065 -
Medicine Jul 2018Paraganglioma is rare in children and most pheochromocytomas originate in the adrenal gland. (Review)
Review
RATIONALE
Paraganglioma is rare in children and most pheochromocytomas originate in the adrenal gland.
PATIENT CONCERNS
The clinical characteristics, diagnosis, and managements in a 9-year-old boy who presented with vomiting and occasional headache with a blood pressure of 210/170 mm Hg was retrospectively reviewed. CT scan of the chest revealed a 7 × 5-cm-sized soft tissue mass in the left paraspinal area. Biochemical reports revealed elevated levels of serum norepinephrine, urine norepinephrine, urine dopamine, and serum neuron specific enolase.
DIAGNOSES
The immunohistochemical studies suggested that the tumor was a paraganglioma of the posterior mediastinum.
INTERVENTIONS
The patient underwent mass resection with thoracotomy. Before operation, the patient was prepared by orally administering captopril, propranolol hydrochloride, and phenoxybenzamine. Body fluid volume was also prepared by vein and mouth in 3 days.
OUTCOMES
The patient was followed up postoperatively for 1 year without recurrence.
LESSONS
We should be highly vigilant the pediatric tumor of the posterior mediastinum with vomiting and headache as the first clinical manifestation.
Topics: Aftercare; Child; Dopamine; Headache; Humans; Hypertension; Male; Mediastinal Neoplasms; Mediastinum; Norepinephrine; Paraganglioma; Phosphopyruvate Hydratase; Retrospective Studies; Thoracotomy; Tomography, X-Ray Computed; Treatment Outcome; Vomiting
PubMed: 29979384
DOI: 10.1097/MD.0000000000011212 -
Clinical Endocrinology Dec 2021Prolonged hypotension is a common complication after resection of pheochromocytoma (PCC) or paraganglioma (PGL). The objective of our study was to identify preoperative...
OBJECTIVE
Prolonged hypotension is a common complication after resection of pheochromocytoma (PCC) or paraganglioma (PGL). The objective of our study was to identify preoperative or intraoperative clinical factors that can predict prolonged hypotension after PCC/PGL resection.
PATIENTS AND METHODS
A total of 414 patients who underwent resection of PCC or PGL at our institution between January 2013 and January 2020 were included. Patients were divided into two groups according to whether or not vasopressor support was required postoperatively. Associations between preoperative and intraoperative variables and prolonged hypotension were evaluated.
RESULTS
Two hundred and one (48.6%) patients had postoperative hypotension that required vasopressor support with a median duration of 20 h. Multivariable analysis demonstrated that increased 24-h urinary norepinephrine (NE) levels (odds ratio [OR] = 1.091, 95% confidence interval [CI]: 1.052-1.132, p < .001), longer operative time (OR = 1.008, CI: 1.004-1.011, p < .001) and lower preoperative phenoxybenzamine dose (OR = 0.336, CI: 0.150-0.753, p = .008) were predictors of prolonged hypotension. Moreover, operative time, body mass index, 24-h urinary level of NE and preoperative phenoxybenzamine dose were significantly correlated with the duration of postoperative vasopressor support.
CONCLUSIONS
Increased urine NE level, longer operative time and lower preoperative phenoxybenzamine dose were predictors of prolonged hypotension requiring vasopressor support. Clinicians can identify these factors to manage their patients better and prevent severe complications.
Topics: Adrenal Gland Neoplasms; Humans; Hypotension; Paraganglioma; Pheochromocytoma; Retrospective Studies
PubMed: 34160851
DOI: 10.1111/cen.14542 -
Journal of Surgical Oncology Sep 2018The safety of laparoscopic resection of very large pheochromocytomas is unclear, and preoperative preparation may benefit from refinement. This retrospective study was... (Clinical Trial)
Clinical Trial
BACKGROUND AND OBJECTIVES
The safety of laparoscopic resection of very large pheochromocytomas is unclear, and preoperative preparation may benefit from refinement. This retrospective study was designed to determine the correlation between tumor size and perioperative characteristics by evaluating data from patients who underwent laparoscopic resection of pheochromocytomas.
METHODS
A total of 253 patients were grouped according to their tumor diameter: diameter ≥8 cm, Glarge (G ) (n = 30); diameter 6 to 8 cm, Gmedium (G ) (n = 57); and diameter <6 cm, Gsmall (G ) (n = 166). The perioperative data were compared among the three groups using the analysis of variance test, Wilcoxon's rank-sum test, and the chi-square test.
RESULTS
Patients in the G and G groups had a higher preoperative phenoxybenzamine daily dose and 24-hour urine levels of noradrenaline and adrenaline than those in the G group, as they needed longer vasopressor support. Transfusion of allogeneic blood products was found to be increased in patients of the G group compared with the other two groups and their intensive care unit stays were longer.
CONCLUSIONS
Compared with small-sized pheochromocytomas, laparoscopic resection of medium-sized pheochromocytomas requires vigilant monitoring and resolution of hemodynamic fluctuations. Patients with very large pheochromocytomas are at greater risk of intraoperative bleeding and may benefit from the ensured availability of blood products and intensive postoperative monitoring.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Adult; Disease Management; Female; Follow-Up Studies; Humans; Laparoscopy; Male; Middle Aged; Perioperative Care; Pheochromocytoma; Retrospective Studies; Treatment Outcome
PubMed: 30175399
DOI: 10.1002/jso.25205 -
Journal of Clinical Medicine Dec 2022Perioperative hemodynamic instability is one of the most common adverse events in patients undergoing adrenalectomy for pheochromocytoma. The aim of this study was to...
BACKGROUND
Perioperative hemodynamic instability is one of the most common adverse events in patients undergoing adrenalectomy for pheochromocytoma. The aim of this study was to analyze the impact of perioperative severe hemodynamic instability.
METHODS
We present a retrospective, single-center analysis in a major tertiary hospital of all consecutive patients undergoing elective adrenalectomy from 2005 to 2019 for pheochromocytoma. Severe perioperative hypertension and hypotension were evaluated, defined as changes in blood pressure larger than 30% of the preoperative patient-specific mean arterial pressure (MAP).
RESULTS
Unilateral adrenalectomy was performed in 67 patients. Intraoperative episodes of hemodynamic instability occurred in 97% of all patients ( = 65), severe hypertension occurred in 24 patients (36%), and severe hypotensive episodes occurred in 62 patients (93%). Patients with more than five severe hypotensive episodes ( = 29) received higher preoperative alpha-adrenergic blockades (phenoxybenzamine 51 ± 50 mg d vs. 29 ± 27 mg d; = 0.023) and had a longer mean ICU stay (39.6 ± 41.5 h vs. 20.6 ± 19.1 h, = 0.015).
CONCLUSION
Intraoperative hypotensive, rather than hypertensive, episodes occurred during adrenalectomy. The occurrence of more than five hypotensive episodes correlated well with a significantly longer hospital stay and ICU time.
PubMed: 36556087
DOI: 10.3390/jcm11247471 -
Frontiers in Cellular Neuroscience 2017Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic,...
Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic, causing the death of sensory hair cells in the inner ear. Strategies aimed at developing or discovering agents that protect against aminoglycoside ototoxicity have focused on inhibiting apoptosis or more recently, on preventing antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds using the larval zebrafish lateral line identified phenoxybenzamine as a potential protectant for aminoglycoside-induced hair cell death. Here we used live imaging of FM1-43 uptake as a proxy for aminoglycoside entry, combined with hair-cell death assays to evaluate whether phenoxybenzamine can protect mammalian cochlear hair cells from the deleterious effects of the aminoglycoside antibiotic neomycin. We show that phenoxybenzamine can block FM1-43 entry into mammalian hair cells in a reversible and dose-dependent manner, but pre-incubation is required for maximal inhibition of entry. We observed differential effects of phenoxybenzamine on FM1-43 uptake in the two different types of cochlear hair cell in mammals, the outer hair cells (OHCs) and inner hair cells (IHCs). The requirement for pre-incubation and reversibility suggests an intracellular rather than an extracellular site of action for phenoxybenzamine. We also tested the efficacy of phenoxybenzamine as an otoprotective agent. In mouse cochlear explants the hair cell death resulting from 24 h exposure to neomycin was steeply dose-dependent, with 50% cell death occurring at ~230 μM for both IHC and OHC. We used 250 μM neomycin in subsequent hair-cell death assays. At 100 μM with 1 h pre-incubation, phenoxybenzamine conferred significant protection to both IHCs and OHCs, however at higher concentrations phenoxybenzamine itself showed clear signs of ototoxicity and an additive toxic effect when combined with neomycin. These data do not support the use of phenoxybenzamine as a therapeutic agent in mammalian inner ear. Our findings do share parallels with the observations from the zebrafish lateral line model but they also highlight the necessity for validation in the mammalian system and the potential for differential effects on sensory hair cells from different species, in different systems and even between cells in the same organ.
PubMed: 28503132
DOI: 10.3389/fncel.2017.00094 -
Behavioural Brain Research Oct 2014The extensive projection of orexigenic neurons and the diffuse expression of orexin receptors suggest that endogenous orexins are involved in several physiological...
The extensive projection of orexigenic neurons and the diffuse expression of orexin receptors suggest that endogenous orexins are involved in several physiological functions of the central nervous system, including learning and memory. Our previous study demonstrated that orexin A improves learning, consolidation and retrieval processes, which involves α- and β-adrenergic, cholinergic, dopaminergic, GABA-A-ergic, opiate and nitrergic neurotransmissions. However, we have little evidence about the action of orexin B on memory processes and the underlying neuromodulation. Therefore, the aim of the present study was to investigate the action of orexin B on passive avoidance learning and the involvement of neurotransmitters in this action in rats. Accordingly, rats were pretreated with the selective orexin 2 receptor (OX2R) antagonist, EMPA; the γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, the bicuculline; a D2, D3, D4 dopamine receptor antagonist, haloperidol; the nonselective opioid receptor antagonist, naloxone; the non-specific nitric oxide synthase (NOS) inhibitor, nitro-l-arginine; the nonselective α-adrenergic receptor antagonist, phenoxybenzamine and the β-adrenergic receptor antagonist, propranolol. Our results demonstrate that orexin B can improve learning, consolidation of memory and retrieval. EMPA reversed completely the action of orexin B on memory consolidation. Bicuculline blocked fully; naloxone, nitro-l-arginine, phenoxybenzamine and propranolol attenuated the orexin B-induced memory consolidation, whereas haloperidol was ineffective. These data suggest that orexin B improves memory functions through OX2R and GABA-ergic, opiate, nitrergic, α- and β-adrenergic neurotransmissions are also involved in this action.
Topics: Adrenergic Antagonists; Animals; Avoidance Learning; Dopamine Antagonists; GABA-A Receptor Antagonists; Intracellular Signaling Peptides and Proteins; Male; Memory; Narcotic Antagonists; Neuropeptides; Neurotransmitter Agents; Nitric Oxide Synthase; Orexin Receptor Antagonists; Orexin Receptors; Orexins; Rats, Wistar; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4; Receptors, GABA-A; Receptors, Opioid; Synaptic Transmission
PubMed: 24931796
DOI: 10.1016/j.bbr.2014.06.016 -
PloS One 2015Drug repositioning has shorter developmental time, lower cost and less safety risk than traditional drug development process. The current study aims to repurpose...
Drug repositioning has shorter developmental time, lower cost and less safety risk than traditional drug development process. The current study aims to repurpose marketed drugs and clinical candidates for new indications in diabetes treatment by mining clinical 'omics' data. We analyzed data from genome wide association studies (GWAS), proteomics and metabolomics studies and revealed a total of 992 proteins as potential anti-diabetic targets in human. Information on the drugs that target these 992 proteins was retrieved from the Therapeutic Target Database (TTD) and 108 of these proteins are drug targets with drug projects information. Research and preclinical drug targets were excluded and 35 of the 108 proteins were selected as druggable proteins. Among them, five proteins were known targets for treating diabetes. Based on the pathogenesis knowledge gathered from the OMIM and PubMed databases, 12 protein targets of 58 drugs were found to have a new indication for treating diabetes. CMap (connectivity map) was used to compare the gene expression patterns of cells treated by these 58 drugs and that of cells treated by known anti-diabetic drugs or diabetes risk causing compounds. As a result, 9 drugs were found to have the potential to treat diabetes. Among the 9 drugs, 4 drugs (diflunisal, nabumetone, niflumic acid and valdecoxib) targeting COX2 (prostaglandin G/H synthase 2) were repurposed for treating type 1 diabetes, and 2 drugs (phenoxybenzamine and idazoxan) targeting ADRA2A (Alpha-2A adrenergic receptor) had a new indication for treating type 2 diabetes. These findings indicated that 'omics' data mining based drug repositioning is a potentially powerful tool to discover novel anti-diabetic indications from marketed drugs and clinical candidates. Furthermore, the results of our study could be related to other disorders, such as Alzheimer's disease.
Topics: Adrenergic alpha-2 Receptor Antagonists; Cyclooxygenase 2 Inhibitors; Data Mining; Databases, Pharmaceutical; Diabetes Mellitus; Drug Repositioning; Gene Expression Profiling; Genome-Wide Association Study; Humans; Hypoglycemic Agents; Metabolomics; Proteomics; Receptors, N-Methyl-D-Aspartate
PubMed: 25946000
DOI: 10.1371/journal.pone.0126082