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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 -
International Journal of Surgery... May 2023Surgical resection of pheochromocytomas and paragangliomas (PPGLs) is associated with a significant risk of intraoperative hemodynamic instability and cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surgical resection of pheochromocytomas and paragangliomas (PPGLs) is associated with a significant risk of intraoperative hemodynamic instability and cardiovascular complications. α-blockade remains the routine preoperative medical preparation despite controversies over the lack of evidence. We presented an updated meta-analysis to ulteriorly evaluate the potential efficacy of preoperative α-blockade versus no blockade for PPGL patients undergoing surgery.
MATERIALS AND METHODS
Randomized and nonrandomized comparative studies assessing preoperative α-blockade for PPGL surgery in adults were identified through a systematic literature search via MEDLINE, Embase, Web of Science, and CENTRAL up to November 2022. Outcome data of intraoperative hemodynamic parameters and major postoperative events were extracted. Mean difference and risk ratio were synthesized as appropriate for each outcome to determine the cumulative effect size.
RESULTS
Fifteen nonrandomized studies involving 3542 patients were finally eligible. Intraoperatively, none of the analyzed hemodynamic parameters differed between patients with or without α-blockade: maximum and minimum systolic blood pressure, hypertensive and hypotensive hemodynamic instability episodes, and peak heart rate, subgroup analysis of normotensive PPGL patients yielded similar results with the overall effects. Postoperatively, α-blockade was associated with prolonged hypotension and vasopressor usage (risk ratio: 4.21, 95% CI: 1.17-15.18, P =0.03). ICU admission, length of stay, overall cardiovascular morbidity, and mortality were similar between the two groups.
CONCLUSIONS
Preoperative α-blockade ensured neither more stable intraoperative hemodynamics nor better perioperative outcome over no blockade for PPGL surgery. However, large-volume randomized controlled trials are still warranted to ascertain these findings.
Topics: Adult; Humans; Pheochromocytoma; Paraganglioma; Hypotension; Blood Pressure; Adrenal Gland Neoplasms; Randomized Controlled Trials as Topic
PubMed: 37037514
DOI: 10.1097/JS9.0000000000000390 -
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 -
Frontiers in Oncology 2018Although gangliocytic paraganglioma (GP) is considered a rare benign neuroendocrine tumor, cases of mortality have been reported. Occasionally, GP is misdiagnosed as...
Although gangliocytic paraganglioma (GP) is considered a rare benign neuroendocrine tumor, cases of mortality have been reported. Occasionally, GP is misdiagnosed as neuroendocrine tumor G1, which is associated with a poorer prognosis than GP. To avoid such misdiagnoses, it is important to understand the clinicopathological characteristics of GP. Thus, herein, we discuss the current literature on the clinicopathological characteristics of GP. We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed and Japana Centra Revuo Medicina searches were used to identify papers describing GP. Inclusion criteria included confirmation of epithelioid, spindle-shaped, and ganglion-like cells in the main article and/or figures and whether the paper was cited in other studies of GP. Data were collected on age, sex, site of the primary lesion, tumor size, treatment, prognosis, lymph node metastasis (LNM), depth of tumor invasion, rate of preoperative diagnosis, and clinical symptoms. In total, 162 papers containing 263 cases of GP met the criteria. The mean age at diagnosis was 53.5 years. The male-to-female ratio was 157:104. The mean tumor size was 25.7 mm. The predominant site of the primary tumor was the duodenum (89.7%). The most common clinical sign of GP was gastrointestinal bleeding (47.9%). Other signs and symptoms of GP included abdominal pain (44.7%), anemia (20.3%), incidental findings (12.9%), nausea (6.9%), weight loss (5.5%), general fatigue (5.1%), jaundice (4.6%), and incidental autopsy findings (5.1%). LNM was observed in 11.4% of patients. Liver metastasis was observed in 1.1% of patients. Depth of tumor invasion (penetrating beyond the submucosal layer or sphincter of Oddi) was by far the most significant risk factor for LNM in patients with GP. This suggests, along with histological heterogeneity, that GP may have hamartomatous characteristics. Furthermore, immunohistochemical expression of progesterone receptor and pancreatic polypeptide were useful in distinguishing between GP and neuroendocrine tumor G1, even in small biopsy specimens. We reveal the clinicopathological characteristics of GP, including risk factors for LNM, differential diagnostic approaches, and improvements in the clinical management of this tumor.In addition, GP may have hamartomatous characteristics.
PubMed: 30101131
DOI: 10.3389/fonc.2018.00291 -
Endocrine Connections Nov 2021Risk of metastatic disease in the cluster 2-related pheochromocytoma/paraganglioma (PPGL) is low. In MEN2 patients, identification of origin of metastases from...
Risk of metastatic disease in the cluster 2-related pheochromocytoma/paraganglioma (PPGL) is low. In MEN2 patients, identification of origin of metastases from pheochromocytoma (PCC) or medullary thyroid carcinoma (MTC) is challenging as both are of neuroendocrine origin. We aim to describe our experience and perform a systematic review to assess prevalence, demographics, biochemistry, diagnostic evaluation, management, and predictors of cluster 2-related metastatic PPGL. Retrospective analysis of 3 cases from our cohort and 43 cases from world literature was done. For calculation of prevalence, all reported patients (n = 3063) of cluster 2 were included. We found that the risk of metastasis in cluster 2-related PPGL was 2.6% (2% in RET, 5% in NF1, 4.8% in TMEM127 and 16.7% in MAX variation). In metastatic PCC in MEN2, median age was 39 years, bilateral tumors were present in 71% and median tumor size was 9.7 cm (range 4-19) with 43.5% mortality. All patients had a primary tumor size ≥4 cm. Origin of primary tumor was diagnosed by histopathology of metastatic lesion in 11 (57.9%), 131I-MIBG scan in 6 (31.6%), and selective venous sampling and CT in 1 (5.3%) patient each. In subgroup of neurofibromatosis 1 (NF1), median age was 46 years (range 14-59) with median tumor size 6 cm and 57% mortality. To conclude, the risk of metastatic disease in cluster 2-related PPGL is low, being especially high in tumors with size ≥4 cm and associated with high mortality. One-third patients of NF1 with metastatic PPGL had presented in second decade of life. Long-term studies are needed to formulate management recommendations.
PubMed: 34662294
DOI: 10.1530/EC-21-0455 -
World Neurosurgery May 2022Primary spine paragangliomas are rare tumors. Surgical resection plays a role, but aggressive lesions are challenging. We reviewed the literature on primary spine... (Review)
Review
BACKGROUND
Primary spine paragangliomas are rare tumors. Surgical resection plays a role, but aggressive lesions are challenging. We reviewed the literature on primary spine paragangliomas.
METHODS
PubMed, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies on primary spine paragangliomas. Clinical-radiologic features, treatments, and outcomes were analyzed and compared between cauda equina versus non-cauda equina tumors.
RESULTS
We included 143 studies comprising 334 patients. Median age was 46 years (range, 6-85 years). The most frequent symptoms were lower back (64.1%) and radicular (53.9%) pain, and sympathetic in 18 patients (5.4%). Cauda equina paragangliomas (84.1%) had frequently lumbar (49.1%) or lumbosacral (29%) locations. Non-cauda equina tumors were mostly in the thoracic (11.4%), thoracolumbar (5.1%), and cervical (3.6%) spine. Median tumor diameter was 2.5 cm (range, 0.5-13.0 cm). Surgical resection (98.5%) was preferred over biopsy (1.5%). Decompressive laminectomy (53%) and spine fusion (6.9%) were also performed. Adjuvant radiotherapy was delivered in 39 patients (11.7%) with aggressive tumors. Posttreatment symptomatic improvement was described in 86.2% cases. Median follow-up was 19.5 months (range, 0.1-468.0 months), and 23 patients (3.9%) had tumor recurrences. No significant differences were found between cauda equina versus non-cauda equina tumors.
CONCLUSIONS
Surgical resection is effective and safe in treating primary spine paragangliomas; however, adjuvant treatments may be needed for aggressive lesions.
Topics: Cauda Equina; Humans; Lumbosacral Region; Middle Aged; Neoplasm Recurrence, Local; Paraganglioma; Paraganglioma, Extra-Adrenal; Spinal Neoplasms; Spine
PubMed: 35123022
DOI: 10.1016/j.wneu.2022.01.110 -
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 -
Journal of Medical Genetics Apr 2020Pheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding subunits of succinate dehydrogenase (SDHA, SDHB, SDHC and SDHD) and assembly factor (SDHAF2) are the most relevant. However, the risk of metastasis posed by these mutations is not reported except for SDHB and SDHD mutations. This study aimed to update the metastatic risks, considering prevalence and incidence of each SDHx mutation, which were dealt formerly all together.
METHODS
We searched EMBASE and MEDLINE and selected 27 articles. The patients included in the studies were divided into three groups depending on the presence of PPGL. We checked the heterogeneity between studies and performed a meta-analysis using Hartung-Knapp-Sidik-Jonkman method based on a random effect model.
RESULTS
The highest PPGL prevalence was for SDHB mutation, ranging from 23% to 31%, and for SDHC mutation (23%), followed by that for SDHA mutation (16%). The lowest prevalence was for SDHD mutation, ranging from 6% to 8%. SDHAF2 mutation showed no metastatic events. The PPGL incidence showed a tendency similar to that of its prevalence with the highest risk of metastasis posed by SDHB mutation (12%-41%) and the lowest risk by SDHD mutation (~4%).
CONCLUSION
There was no integrated evidence of how SDHx mutations are related to metastatic PPGL. However, these findings suggest that SDHA, SDHB and SDHC mutations are highly associated and should be tested as indicators of metastasis in patients with PPGL.
Topics: Adrenal Gland Neoplasms; Electron Transport Complex II; Germ-Line Mutation; Heterozygote; Humans; Membrane Proteins; Mitochondrial Proteins; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 31649053
DOI: 10.1136/jmedgenet-2019-106324 -
Radiotherapy and Oncology : Journal of... Feb 2013The primary treatment goal of radiotherapy for paragangliomas of the head and neck region (HNPGLs) is local control of the tumor, i.e. stabilization of tumor volume.... (Meta-Analysis)
Meta-Analysis Review
The primary treatment goal of radiotherapy for paragangliomas of the head and neck region (HNPGLs) is local control of the tumor, i.e. stabilization of tumor volume. Interestingly, regression of tumor volume has also been reported. Up to the present, no meta-analysis has been performed giving an overview of regression rates after radiotherapy in HNPGLs. The main objective was to perform a systematic review and meta-analysis to assess regression of tumor volume in HNPGL-patients after radiotherapy. A second outcome was local tumor control. Design of the study is systematic review and meta-analysis. PubMed, EMBASE, Web of Science, COCHRANE and Academic Search Premier and references of key articles were searched in March 2012 to identify potentially relevant studies. Considering the indolent course of HNPGLs, only studies with ≥ 12 months follow-up were eligible. Main outcomes were the pooled proportions of regression and local control after radiotherapy as initial, combined (i.e. directly post-operatively or post-embolization) or salvage treatment (i.e. after initial treatment has failed) for HNPGLs. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Pooled proportions with 95% confidence intervals (CI) were reported. Fifteen studies were included, concerning a total of 283 jugulotympanic HNPGLs in 276 patients. Pooled regression proportions for initial, combined and salvage treatment were respectively 21%, 33% and 52% in radiosurgery studies and 4%, 0% and 64% in external beam radiotherapy studies. Pooled local control proportions for radiotherapy as initial, combined and salvage treatment ranged from 79% to 100%. Radiotherapy for jugulotympanic paragangliomas results in excellent local tumor control and therefore is a valuable treatment for these types of tumors. The effects of radiotherapy on regression of tumor volume remain ambiguous, although the data suggest that regression can be achieved at least in some patients. More research is needed to identify predictors for treatment success.
Topics: Bias; Brain Neoplasms; Humans; Paraganglioma; Radiotherapy Dosage; Temporal Lobe; Tumor Burden
PubMed: 23332889
DOI: 10.1016/j.radonc.2012.11.002