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Endocrine-related Cancer Jul 2023Core needle biopsy (CNB) has been used with caution in pheochromocytoma and paraganglioma (PPGL) due to concerns about catecholamine-related complications. While it is... (Meta-Analysis)
Meta-Analysis
Core needle biopsy (CNB) has been used with caution in pheochromocytoma and paraganglioma (PPGL) due to concerns about catecholamine-related complications. While it is unclear what scientific evidence supports this claim, it has limited the acquisition of biological samples for diagnostic purposes and research, especially in metastatic PPGL. We performed a systematic review and individual patient meta-analysis to evaluate the risk of complications after CNB in PPGL patients. The primary and secondary objectives were to investigate the risk of death and the occurrence of complications requiring intervention or hospitalization, respectively. Fifty-six articles describing 86 PPGL patients undergoing CNB were included. Of the patients (24/71), 34% had metastases and 53.4% (31/58) had catecholamine-related symptoms before CNB. Of the patients (14/41), 34.1% had catecholamine excess testing prior to the biopsy. No CNB-related deaths were reported. Four patients (14.8%, 4/27) experienced CNB-related complications requiring hospitalization or intervention. One case had a temporary duodenal obstruction caused by hematoma, two cases had myocardial infarction, and one case had Takotsubo cardiomyopathy. Eight patients (32%, 8/25) had CNB-related catecholamine symptoms, mainly transient hypertension, excessive diaphoresis, tachycardia, or hypertensive crisis. The scientific literature does not allow us to make any firm conclusion on the safety of CNB in PPGL. However, it is reasonable to argue that CNB could be conducted after thorough consideration, preparation, and with close follow-up for PPGL patients with a strong clinical indication for such investigation.
Topics: Humans; Pheochromocytoma; Biopsy, Large-Core Needle; Paraganglioma; Catecholamines; Adrenal Gland Neoplasms; Retrospective Studies
PubMed: 37185155
DOI: 10.1530/ERC-22-0354 -
Neurosurgical Review Apr 2021Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without... (Meta-Analysis)
Meta-Analysis
Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56 years (44-69 years). With a median clinical and radiological follow-up of 44 months (9-161 months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p = 0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r = - 0.4, p = 0.001), right-sided tumor (r = - 0.3, p = 0.03), primary SRS (r = - 0.5, p ≤ 0.001), and initial clinical presentation of hearing loss (r = - 0.4, p = 0.001). To achieve a LC ≥ 90%, a median marginal dose (Gy) of 15 (range, 12-30 Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.
Topics: Adult; Aged; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Paraganglioma; Radiosurgery; Treatment Outcome
PubMed: 32318920
DOI: 10.1007/s10143-020-01292-5 -
Endocrine Jun 2017To determine the accuracy of biochemical tests for the diagnosis of pheochromocytoma and paraganglioma. (Review)
Review
Accuracy of recommended sampling and assay methods for the determination of plasma-free and urinary fractionated metanephrines in the diagnosis of pheochromocytoma and paraganglioma: a systematic review.
PURPOSE
To determine the accuracy of biochemical tests for the diagnosis of pheochromocytoma and paraganglioma.
METHODS
A search of the PubMed database was conducted for English-language articles published between October 1958 and December 2016 on the biochemical diagnosis of pheochromocytoma and paraganglioma using immunoassay methods or high-performance liquid chromatography with coulometric/electrochemical or tandem mass spectrometric detection for measurement of fractionated metanephrines in 24-h urine collections or plasma-free metanephrines obtained under seated or supine blood sampling conditions.
RESULTS
Application of the Standards for Reporting of Diagnostic Studies Accuracy Group criteria yielded 23 suitable articles. Summary receiver operating characteristic analysis revealed sensitivities/specificities of 94/93% and 91/93% for measurement of plasma-free metanephrines and urinary fractionated metanephrines using high-performance liquid chromatography or immunoassay methods, respectively. Partial areas under the curve were 0.947 vs. 0.911. Irrespective of the analytical method, sensitivity was significantly higher for supine compared with seated sampling, 95 vs. 89% (p < 0.02), while specificity was significantly higher for supine sampling compared with 24-h urine, 95 vs. 90% (p < 0.03). Partial areas under the curve were 0.942, 0.913, and 0.932 for supine sampling, seated sampling, and urine. Test accuracy increased linearly from 90 to 93% for 24-h urine at prevalence rates of 0.0-1.0, decreased linearly from 94 to 89% for seated sampling and was constant at 95% for supine conditions.
CONCLUSIONS
Current tests for the biochemical diagnosis of pheochromocytoma and paraganglioma show excellent diagnostic accuracy. Supine sampling conditions and measurement of plasma-free metanephrines using high-performance liquid chromatography with coulometric/electrochemical or tandem mass spectrometric detection provides the highest accuracy at all prevalence rates.
Topics: Adrenal Gland Neoplasms; Chromatography, High Pressure Liquid; Humans; Metanephrine; Paraganglioma; Pheochromocytoma; Sensitivity and Specificity; Specimen Handling; Tandem Mass Spectrometry
PubMed: 28405881
DOI: 10.1007/s12020-017-1300-y -
International Journal of Surgery... Aug 2022This systematic review and meta-analysis compared the safety and effectiveness of minimally invasive adrenalectomy (MIA) with open adrenalectomy (OA) in patients with... (Meta-Analysis)
Meta-Analysis Review
Safety and effectiveness of minimally invasive adrenalectomy versus open adrenalectomy in patients with large adrenal tumors (≥5 cm): A meta-analysis and systematic review.
BACKGROUND
This systematic review and meta-analysis compared the safety and effectiveness of minimally invasive adrenalectomy (MIA) with open adrenalectomy (OA) in patients with large adrenal tumors (≥5 cm).
MATERIALS AND METHODS
We performed a systematic review and cumulative meta-analysis of the primary outcomes according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. Five databases including Medline, PubMed, Cochrane Library, Scopus, and Web of Science were systematically searched. The time frame of the search was set from the creation of the database to March 2022.
RESULTS
Ten studies including 898 patients were included. Compared to OA, MIA is superior for length of stay [LOS WMD = -3.52, 95% CI (-4.61, -2.43), P < 0.01], drainage time [DT WMD = -0.68, 95% CI (-1.27, -0.09), P < 0.05] and fasting time [FT WMD = -0.95, 95% CI (-1.35, -0.55), P < 0.01], estimated blood loss [EBL WMD = -314.22, 95% CI (-494.76, -133.69), P < 0.01] and transfusion [WMD = -416.73, 95% CI (-703.75, -129.72), P < 0.01], while operative time (OT) and complications are not statistically different. For pheochromocytoma, MIA remains superior for LOS [WMD = -3.10, 95% CI (-4.61, -1.60), P < 0.01] and EBL [WMD = -273.65, 95% CI (-457.44, -89.86), P < 0.01], while OT and complications are not significantly different.
CONCLUSION
MIA offers advantages over OA in the management of large adrenal tumors, including in the case of a specific large adrenal tumor - large pheochromocytoma.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Humans; Laparoscopy; Length of Stay; Operative Time; Pheochromocytoma; Treatment Outcome
PubMed: 35870758
DOI: 10.1016/j.ijsu.2022.106779 -
Endocrine-related Cancer May 2019Pheochromocytoma and paraganglioma (PPGL) can be divided into at least four molecular subgroups. Whether such categorizations are independent factors for prognosis or... (Meta-Analysis)
Meta-Analysis
Pheochromocytoma and paraganglioma (PPGL) can be divided into at least four molecular subgroups. Whether such categorizations are independent factors for prognosis or metastatic disease is unknown. We performed a systematic review and individual patient meta-analysis aiming to estimate if driver mutation status can predict metastatic disease and survival. Driver mutations were used to categorize patients according to three different molecular systems: two subgroups (SDHB mutated or wild type), three subgroups (pseudohypoxia, kinase signaling or Wnt/unknown) and four subgroups (tricarboxylic acid cycle, VHL/EPAS1, kinase signaling or Wnt/unknown). Twenty-one studies and 703 patients were analyzed. Multivariate models for association with metastasis showed correlation with SDHB mutation (OR 5.68 (95% CI 1.79-18.06)) as well as norepinephrine (OR 3.01 (95% CI 1.02-8.79)) and dopamine (OR 6.39 (95% CI 1.62-25.24)) but not to PPGL location. Other molecular systems were not associated with metastasis. In multivariate models for association with survival, age (HR 1.04 (95% CI 1.02-1.06)) and metastases (HR 6.13 (95% CI 2.86-13.13)) but neither paraganglioma nor SDHB mutation remained significant. Other molecular subgroups did not correlate with survival. We conclude that molecular categorization accordingly to SDHB provided independent information on the risk of metastasis. Driver mutations status did not correlate independently with survival. These data may ultimately be used to guide current and future risk stratification of PPGL.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Genetic Association Studies; Humans; Mutation; Paraganglioma; Pheochromocytoma; Prognosis
PubMed: 30893643
DOI: 10.1530/ERC-19-0024 -
Endocrine Practice : Official Journal... Oct 2017Various studies have validated plasma free metanephrines (MNs) as biomarkers for pheochromocytoma and paraganglioma (PPGL). This meta-analysis aimed to estimate the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Various studies have validated plasma free metanephrines (MNs) as biomarkers for pheochromocytoma and paraganglioma (PPGL). This meta-analysis aimed to estimate the overall diagnostic accuracy of this biochemical test for PPGL.
METHODS
We searched the PubMed, the Cochrane Library, Web of Science, Embase, Scopus, OvidSP, and ProQuest Dissertations & Theses databases from January 1, 1995 to December 2, 2016 and selected studies written in English that assessed plasma free MNs in the diagnosis of PPGL. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate the quality of the included studies. We calculated pooled sensitivities, specificities, positive and negative likelihood ratios, diagnostic odds ratios (DORs) and areas under curve (AUCs) with their 95% confidence intervals (95% CIs). Heterogeneity was assessed by I. To identify the source of heterogeneity, we evaluated the threshold effect and performed a meta-regression. Deeks' funnel plot was selected for investigating any potential publication bias.
RESULTS
Although the combination of metanephrine (MN) and normetanephrine (NMN) carried lower specificity (0.94, 95% CI 0.90-0.97) than NMN (0.97, 95% CI 0.92-0.99), NMN was generally more accurate than individual tests, with the highest AUC (0.99, 95% CI 0.97-0.99), DOR (443.35, 95% CI 216.9-906.23), and pooled sensitivity (0.97, 95% CI 0.94-0.98) values. Threshold effect and meta-regression analyses showed that different cut-offs, blood sampling positions, study types and test methods contributed to heterogeneity.
CONCLUSION
This meta-analysis suggested an effective value for combined plasma free MNs for the diagnosis of PPGL, but testing for MNs requires more standardization using tightly regulated studies.
ABBREVIATIONS
AUC = area under curve; CI = confidence interval; DOR = diagnostic odds ratio; EIA = enzyme immunoassay; LC-ECD = liquid chromatography-electrochemical detection; LC-MS/MS = liquid chromatography-tandem mass spectrometry; MN = metanephrine; NMN = normetaneprhine; PPGL = pheochromocytoma and paraganglioma; QUADAS-2 = Quality Assessment of Diagnostic Accuracy Studies 2.
Topics: Adrenal Gland Neoplasms; Biomarkers; Chromatography, Liquid; Humans; Immunoenzyme Techniques; Metanephrine; Normetanephrine; Paraganglioma; Pheochromocytoma; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry
PubMed: 28704098
DOI: 10.4158/EP171877.OR -
Frontiers in Oncology 2023Peptide receptor radionuclide therapy (PRRT) for advanced pheochromocytomas and paragangliomas (PPGLs) has received increasing attention. The purpose of this article is...
OBJECTIVE
Peptide receptor radionuclide therapy (PRRT) for advanced pheochromocytomas and paragangliomas (PPGLs) has received increasing attention. The purpose of this article is to evaluate the efficacy and safety of PRRT in patients with metastatic or inoperable PPGLs by meta-analysis.
METHODS
A literature search was conducted in PubMed, Embase, Scopus, and Cochrane Library databases up to November 2022. All articles on PRRT for PPGLs were searched, and appropriate data were included for analysis. The measures evaluated included objective response rate (ORR), disease control rate (DCR), clinical response rate, biochemical response rate, progression-free survival (PFS), overall survival (OS), and adverse events. Statistical analysis was performed using Stata 16.0 and the R programming language, data were combined using a random-effects model, and the results were presented using forest plots.
RESULTS
A total of 20 studies with 330 patients were included in the analysis. The results showed that ORR and DCR were 20.0% (95% CI: 12.0%-28.0%) and 90.0% (95% CI: 85.0%-95.0%), respectively. Clinical and biochemical responses were 74.9% (95% CI: 56.3%-90.2%) and 69.5% (95%CI: 40.2%-92.9%). Median PFS and median OS were 31.79 (95% CI:21.25-42.33) months and 74.30 (95% CI: 0.75-147.84) months, respectively. Any grade of hematotoxicity and nephrotoxicity occurred in 22.3% (95% CI:12.5%-33.5%) and 4.3% (95% CI:0.2%-11.4%) patients. Grade 3-4 hemotoxicity occurred in 4.3% (95% CI:0.2%-11.4%) and grade 3-4 nephrotoxicity in 4/212 patients. Additionally, Treatment was discontinued in 9.0% (95% CI: 0.5%-23.3%) patients and one patient died as a result of a toxicity.
CONCLUSION
Patients with metastatic or inoperable PPGLs can be effectively treated with PRRT, and it has a favorable safety profile.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022359232.
PubMed: 37483516
DOI: 10.3389/fonc.2023.1141648 -
British Journal of Neurosurgery Oct 2023Primary paragangliomas (PGs) are extra-adrenal neuroendocrine tumours that are extremely rare. Multiple lesions in the central nervous system raise suspicion of a... (Review)
Review
AIM
Primary paragangliomas (PGs) are extra-adrenal neuroendocrine tumours that are extremely rare. Multiple lesions in the central nervous system raise suspicion of a metastatic process. Lack of consensus on their management warrants the categorization of existing literature to evaluate management options.
METHODS
A systematic review of the medical literature on paraganglioma within the cranial vault was completed in accordance with PRISMA guidelines using the Medline database. Tumour physical measures, management parameters, and immunohistochemistry of all documented cases of primary and secondary paraganglioma within the cranial vault were descriptively compared. This review was augmented by comparison with our centre's case of a 48-year-old man diagnosed with metastatic PG originating in the cauda equina and seeding in the cerebellum. Histological parameters within the literature was also established.
RESULTS
The systematic literature review yielded published 52 papers. Most prevalent primary intracranial PGs (n = 37) were in the sellar region (78%, n = 23) and the cerebellum (21%, n = 6). The highest progression free survival was seen in primary sellar PGs (87.5% by 34.5 months) and cerebellar PGs (100% by 35.7 months) when treated with adjuvant radiotherapy with subtotal resection or gross total resection, respectively. Contrasting, the most frequent intracranial PGs metastases (n = 15) occurred in the cerebellum (36%, n = 6), and the cerebral parenchyma (29%, n = 4). Their recurrence rate was between 4 and 10% and these metastasized PG in the cerebellum are slow growing (8.9 years, range: 3-22 years). Adjuvant radiotherapy with Gross Total Resection resulted in the optimum progression-free survival (100% up to 48 months) for the patient with PGs metastasis to the cerebellum.
CONCLUSION
Metastatic PGs tend to be slow-growing and are clinically silent tumours. Diagnosed patients should undergo regular surveillance neuroradiological assessment, regardless of symptomatology, for metastases along the complete neural axis. We recommend operative management with GTR and adjunct RT in these patients.
Topics: Male; Humans; Middle Aged; Paraganglioma; Brain Neoplasms; Cerebellar Neoplasms; Peripheral Nervous System Neoplasms; Immunohistochemistry; Paraganglioma, Extra-Adrenal
PubMed: 33739182
DOI: 10.1080/02688697.2021.1902477 -
Otolaryngology--head and Neck Surgery :... Dec 2015There is no definitive consensus on the impact of preoperative embolization on carotid body paraganglioma management. The purpose of this study was to assess the effects... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
There is no definitive consensus on the impact of preoperative embolization on carotid body paraganglioma management. The purpose of this study was to assess the effects of preoperative embolization on carotid body paraganglioma excision.
DATA SOURCES
A systematic search was conducted without limits, and it included studies published on or before July 2013 from PubMed, CINAHL, Web of Knowledge, and the Cochrane Library. Relevant synonyms for the search terms "paraganglioma,""carotid body tumor," and "embolization" were applied.
REVIEW METHODS
Studies evaluating patients undergoing surgical intervention with embolization for carotid body tumors were included. Two reviewers independently assessed the titles and abstracts for inclusion and extracted the data. The guidelines set forth by the Cochrane Collaboration were followed in the process of data extraction. Data were pooled with a fixed effects model, and standardized mean difference (SMD) and 95% confidence intervals (95% CIs) are reported.
RESULTS
A total of 22 studies (15 nonrandomized studies with a comparator, 7 single-arm studies) were included, enrolling 578 patients with 607 tumors. Patients undergoing preoperative embolization had significantly less estimated blood loss compared with those of surgical excision only (12 studies; 295 tumors; SMD: -0.52; 95% CI: -0.77, -0.28). Patients undergoing preoperative embolization had less operative time compared with that of surgical excision only (6 studies; 174 tumors; SMD: -0.46; 95% CI: -0.77, -0.14).
CONCLUSION
Surgical excision with preoperative embolization appears to decrease estimated blood loss and operative time when compared with that without preoperative embolization for carotid body paragangliomas.
Topics: Carotid Body Tumor; Embolization, Therapeutic; Humans; Postoperative Hemorrhage; Preoperative Care
PubMed: 26378186
DOI: 10.1177/0194599815605323 -
The Journal of Clinical Endocrinology... May 2021Treatment of pheochromocytoma and paraganglioma (PPGL) requires preintervention titration of alpha- and beta-adrenergic blockade, but patients may still be at risk for...
CONTEXT
Treatment of pheochromocytoma and paraganglioma (PPGL) requires preintervention titration of alpha- and beta-adrenergic blockade, but patients may still be at risk for complications from catecholamine excess. Metyrosine decreases catecholamine production, making it an attractive therapeutic adjunct for select patients.
EVIDENCE ACQUISITION
A systematic literature review was performed (Ovid Medline and Scopus databases) on December 17, 2019, including studies with humans and original data. Studies with 10 or more patients on metyrosine for PPGL were included. Studies were screened for overlapping populations, and the most comprehensive study was included. The references of included studies were reviewed for additional data. Patient data from our institution between 2000 and 2015 were also reviewed.
EVIDENCE SYNTHESIS
Metyrosine is well tolerated when used for a short course and can improve intraoperative outcomes in PPGL. Metyrosine should be considered when a difficult PPGL resection is expected (eg, pericardiac paraganglioma, abdominal paraganglioma with great vessel involvement), a large release of catecholamines is anticipated (eg, ablative therapy, chemotherapy), or when standard alpha- and beta-adrenergic blockade are not tolerated or cannot adequately control hypertension. Side effects are generally mild and self-limited, with sedation in a majority of patients. Extrapyramidal side effects are rare but can limit use of metyrosine. Because of its expense and limited availability, metyrosine use should be carefully planned and timed in relation to surgery.
CONCLUSIONS
Metyrosine is a safe addition to traditional alpha- and beta-adrenergic blockade and should be considered in those patients with PPGL at high risk for acute release of catecholamines.
Topics: Adrenal Gland Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Humans; Hypertension; Paraganglioma; Pheochromocytoma; alpha-Methyltyrosine
PubMed: 33693908
DOI: 10.1210/clinem/dgab130