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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 -
Wideochirurgia I Inne Techniki... Mar 2023To compare the efficacy and safety of retroperitoneal laparoscopic adrenalectomy (RLA) vs. transperitoneal laparoscopic adrenalectomy (TLA) for pheochromocytoma (PHEO).
INTRODUCTION
To compare the efficacy and safety of retroperitoneal laparoscopic adrenalectomy (RLA) vs. transperitoneal laparoscopic adrenalectomy (TLA) for pheochromocytoma (PHEO).
AIM
To perform a systematic review and meta-analysis to evaluate the efficacy and safety of RLA versus TLA for PHEO.
MATERIAL AND METHODS
A systematic research of PubMed, Ovid, Scopus (up to June 2022), and citation lists was performed for all comparative eligible studies of RLA versus TLA for PHEO. Statistical analysis was performed using RevMan 5.4.
RESULTS
Overall, six studies including 597 patients (RLA 243; TLA 354) were included. RLA was associated with lower BMI compared to TLA (WMD = -0.81 kg/m, 95% CI: -1.53 to -0.10; p = 0.03). RLA was associated with smaller tumor size (WMD = -0.90 cm, 95% CI: -1.59 to -0.20; p = 0.01). RLA was associated with shorter operative time (WMD = -34.58 min, 95% CI: -40.80 to -28.36; p < 0.001), lower EBL (WMD = -107.91 ml, 95% CI: -145.09, -70.74; p < 0.001), and a slightly higher HI rate (OR = 1.54, 95% CI: 1.03 to 2.29; p = 0.03). There were no statistically significant differences for complications (p = 0.71) and Clavien-Dindo score ≥ 3 complications (p = 0.19) for RLA compared to TLA. RLA was associated with shorter length of hospital stay (WMD = -1.94 days, 95% CI: -2.60 to -1.29; p < 0.001).
CONCLUSIONS
For selected PHEO patients, RLA has advantages in terms of operative time, EBL, and length of hospital stay, but the HI rate is higher. Since the lower BMI and smaller tumor size of RLA reduced the difficulty of surgery, these results need to be confirmed by further studies.
PubMed: 37064558
DOI: 10.5114/wiitm.2022.120419 -
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 -
The Journal of Clinical Endocrinology... Aug 2023Adrenal medullary hyperplasia (AMH) is a rare, incompletely described disorder of the adrenal medulla that is associated with catecholamine excess. (Meta-Analysis)
Meta-Analysis
CONTEXT
Adrenal medullary hyperplasia (AMH) is a rare, incompletely described disorder of the adrenal medulla that is associated with catecholamine excess.
OBJECTIVE
To increase knowledge about AMH by reviewing the reported cases of this disorder.
DESIGN
Systematic review and meta-analysis of the genotype/phenotype relationship in all reported cases of AMH.
SETTING
Literature review and analysis.
PATIENTS OR OTHER PARTICIPANTS
All cases of AMH published to date.
MAIN OUTCOME MEASURE(S)
Characteristics of AMH cases and genotype-phenotype relationships.
RESULTS
A total of 66 patients, median age of 48 years, were identified from 29 reports. More than one-half were male (n = 39, 59%). The majority had unilateral (73%, n = 48) disease; 71% (n = 47) were sporadic and 23% (n = 15) were associated with the MEN2. Most (91%, n = 60) displayed signs and symptoms of excess catecholamine secretion, particularly hypertension. Elevated catecholamine concentrations (86%, n = 57) and adrenal abnormalities on imaging were common (80%, n = 53). More than one-half (58%, n = 38) had concurrent tumors: pheochromocytoma (42%, n = 16/38); medullary thyroid cancer (24%, n = 9/38); and adrenocortical adenoma (29%, n = 11/38). Most (88%, n = 58) underwent adrenalectomy with 45/58 achieving symptom resolution. Adrenalectomy was less common in patients under 40 years and those with bilateral disease (both P < .05).
CONCLUSION
AMH may be sporadic or associated with MEN2, most have catecholamine excess and imaging abnormalities. Unilateral involvement is more common. Most reported patients have been treated with adrenalectomy, which is usually curative with regard to catecholamine hypersecretion.
Topics: Male; Humans; Female; Hyperplasia; Adrenal Gland Neoplasms; Pheochromocytoma; Adrenal Medulla; Adrenalectomy; Catecholamines
PubMed: 36896586
DOI: 10.1210/clinem/dgad121 -
International Journal of Surgery... May 2023The effectiveness and safety of laparoscopic adrenalectomy (LA) under different routes for the treatment of large pheochromocytomas (PCCs) is unknown. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effectiveness and safety of laparoscopic adrenalectomy (LA) under different routes for the treatment of large pheochromocytomas (PCCs) is unknown.
MATERIALS AND METHODS
This meta-analysis and systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. Three databases were systematically searched, including Medline, PubMed, and Web of Science. The time frame of the search was set from the creation of the database to October 2022. Perioperative outcomes were divided into two groups according to tumor size: SMALL group (≤6 cm in diameter), LARGE group (>6 cm in diameter).
RESULTS
Eight studies including 600 patients were included. In the LA group, complications was comparable in both groups (SMALL group and LARGE group), and the LARGE group had longer operative time [OT weighted mean difference (WMD)=32.55; 95% CI: 11.17, 53.92; P <0.01], length of stay (LOS WMD=0.82; 95% CI: 0.19, 1.44; P <0.05), more estimated blood loss (EBL WMD=85.26; 95% CI: 20.71, 149.82; P <0.05), hypertension [odds ratio (OR)=3.99; 95% CI: 1.84, 8.65; P <0.01], hypotension (OR=1.84; 95% CI: 1.11, 3.05; P <0.05), and conversion (OR=5.60; 95% CI: 1.56, 20.13; P <0.01). In the transabdominal LA group, OT, LOS, EBL, complications, hypertension, and hypotension were the same in both groups. In the retroperitoneal LA group, complications and hypotension were the same in both groups, while the LARGE group had longer OT (WMD=52.07; 95% CI: 26.95, 77.20; P <0.01), LOS (WMD=0.51; 95% CI: 0.00, 1.01; P <0.05), more EBL (WMD=92.99; 95% CI: 27.70, 158.28; P <0.01) and higher rates of hypertension (OR=6.03; 95% CI: 1.95, 18.61; P <0.01).
CONCLUSIONS
LA remains a safe and effective approach for large PCC. Transabdominal LA is superior to retroperitoneal LA.
Topics: Humans; Laparoscopy; Adrenalectomy; Pheochromocytoma; Adrenal Gland Neoplasms; Hypertension; Hypotension; Treatment Outcome; Length of Stay
PubMed: 37037515
DOI: 10.1097/JS9.0000000000000389 -
Gland Surgery Jun 2020Pheochromocytomas (PHEOs) are neural crest cell tumors producing catecholamines. PHEOS need to be early diagnosed and adequately managed. Adrenalectomy is the gold... (Review)
Review
Pheochromocytomas (PHEOs) are neural crest cell tumors producing catecholamines. PHEOS need to be early diagnosed and adequately managed. Adrenalectomy is the gold standard treatment of these type of tumors. There has been major improvement of surgical technologies with the development of laparoscopic and robotic systems these past several years. We conducted a review of the literature to evaluate the robotic approach for adrenalectomy for patients with PHEO.
PubMed: 32775278
DOI: 10.21037/gs-2019-ra-05 -
Journal of Endocrinological... Nov 2021Information on systolic dysfunction, as assessed by left-ventricular (LV) mechanics, in patients with pheochromocytoma after surgical treatment is scanty. We performed a... (Meta-Analysis)
Meta-Analysis
AIM
Information on systolic dysfunction, as assessed by left-ventricular (LV) mechanics, in patients with pheochromocytoma after surgical treatment is scanty. We performed a systematic meta-analysis of speckle tracking echocardiographic studies to provide an updated comprehensive information on this issue.
METHODS
The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search for articles published from the inception up to May 31st 2021. Studies were identified using MeSH terms and crossing the following search items: "myocardial strain" "left ventricular mechanics", "speckle tracking echocardiography", "systolic dysfunction", "pheochromocytoma", and "paraganglioma".
RESULTS
A total of 92 surgically treated patients with pheochromocytoma/paraganglioma were included in 3 longitudinal studies. Successful surgical treatment was associated with a decrease in relative wall thickness (SMD - 0.25 ± 0.10, CI - 0.45/- 0.05, p < 0.01) and an improvement in global longitudinal strain (SMD - 0.45 ± 0.10, CI - 0.66/- 0.24, p < 0.0001). The favorable effects of treatment on LV geometry and mechanics were not accompanied by significant changes in ejection fraction (SMD - 0.07 ± 0.10, CI - 0.27/0.12, p = 0.44).
CONCLUSIONS
This meta-analysis adds a new piece of evidence, suggesting that surgical treatment of patients with pheochromocytoma impacts favorably on LV geometry and LV mechanics, and, more importantly, the assessment of LV changes in this setting can no longer rely on conventional echocardiographic parameters such as ejection fraction.
Topics: Adrenal Gland Neoplasms; Echocardiography; Heart Ventricles; Humans; Outcome Assessment, Health Care; Paraganglioma; Pheochromocytoma; Surgical Procedures, Operative; Ventricular Dysfunction, Left
PubMed: 34235707
DOI: 10.1007/s40618-021-01631-3 -
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 -
Frontiers in Endocrinology 2022Targeted radionuclide therapy (TRT) with [I]MIBG and [Lu]Lu-DOTA-TATE is an alternative treatment to the classic schemes in slow progressive metastatic/inoperable...
Response to targeted radionuclide therapy with [I]MIBG AND [Lu]Lu-DOTA-TATE according to adrenal vs. extra-adrenal primary location in metastatic paragangliomas and pheochromocytomas: A systematic review.
PURPOSE
Targeted radionuclide therapy (TRT) with [I]MIBG and [Lu]Lu-DOTA-TATE is an alternative treatment to the classic schemes in slow progressive metastatic/inoperable paraganglioma (PGL) and pheochromocytoma (PHEO). There is no consensus on which treatment to administer and/or the best sequence in patients who are candidates for both therapies. To clarify these questions, this systematic review assesses the prognostic value of [I]MIBG and Lu]Lu-DOTA-TATE (PRRT-Lu) treatments in terms of progression-free survival (PFS) both globally and considering the primary location.
METHODS
This review was developed according to the PRISMA Statement with 27 final studies (608 patients). Patient characteristics, treatment procedure, and follow-up criteria were evaluated. In addition, a Bayesian linear regression model weighted according to its sample size and an alternative model, which also included an interaction between the treatment and the proportion of PHEOs, were carried out, adjusted by a Student's distribution.
RESULTS
In linear regression models, [I]MIBG overall PFS was, on average, 10 months lower when compared with PRRT-Lu. When considering the interaction between treatment responses and the proportion of PHEOs, PRRT-Lu showed remarkably better results in adrenal location. The PFS of PRRT-Lu was longer when the ratio of PHEOs increased, with a decrease in [I]MIBG PFS by 1.9 months for each 10% increase in the proportion of PHEOs in the sample.
CONCLUSION
Methodology, procedure, and PFS from the different studies are quite heterogeneous. PRRT-Lu showed better results globally and specifically in PHEOs. This fact opens the window to prospective trials comparing or sequencing [I]MIBG and PRRT-Lu.
Topics: Humans; Pheochromocytoma; 3-Iodobenzylguanidine; Bayes Theorem; Prospective Studies; Radiopharmaceuticals; Paraganglioma; Adrenal Gland Neoplasms; Iodine Radioisotopes
PubMed: 36339441
DOI: 10.3389/fendo.2022.957172 -
Journal of Neuroendocrinology Dec 2023Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to...
Safety and efficacy of peptide receptor radionuclide therapy in patients with advanced pheochromocytoma and paraganglioma: A single-institution experience and review of the literature.
INTRODUCTION
Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to evaluate the safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced PPGL, based on a single-institution experience and provide a comprehensive review of the literature.
METHODS
A retrospective analysis was conducted on patients with advanced pheochromocytoma and paraganglioma who received PRRT at a single institution from April 2012 to March 2022. Clinical characteristics, treatment response, adverse events, and survival outcomes were assessed. A systematic literature review was also performed.
RESULTS
A total of 15 patients with advanced PPGL were included, the majority of whom had both metastatic and functional disease. Most patients received four infusions of 177Lu-DOTATATE (73%). The median therapeutic 177Lu-DOTATATE radioactivity for each infusion was 7.4 GBq. Only one patient was treated with one infusion of 90Y-DOTATATE (4.2 GBq) in addition to three infusions of Lu-177 DOTATATE. Overall, PRRT suggests a promising efficacy with disease control rate of 63.6% by RECIST v1.1. The median overall survival (OS) was not reached and the median progression free survival (PFS) was 25.9 months. In terms of safety, PRRT was well tolerated. Review of the literature revealed consistent findings, supporting the efficacy and safety of PRRT in PPGL.
CONCLUSION
This study suggests that PRRT is a safe and effective therapeutic option for patients with PPGL. Our findings align with the existing literature, providing additional evidence to support the use of PRRT in this challenging patient population.
Topics: Humans; Pheochromocytoma; Yttrium Radioisotopes; Retrospective Studies; Paraganglioma; Adrenal Gland Neoplasms; Receptors, Peptide
PubMed: 37937484
DOI: 10.1111/jne.13349