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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 -
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 -
Clinical Endocrinology Nov 2017The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta-analysis of baseline... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta-analysis of baseline characteristics and mortality rates of patients with metastatic PHEO and PGL (PPGL).
DESIGN
Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, Web of Science, and references of key articles were searched from inception to 2016.
PATIENTS
Studies comprised ≥20 patients with metastatic PPGL and reported baseline characteristics and follow-up data.
MEASUREMENTS
Reviewers extracted standardized data and assessed risk of bias using a modified Newcastle-Ottawa tool. Random-effects meta-analysis was used to pool event rates across studies.
RESULTS
Twenty retrospective noncomparative studies reported on 1338 patients with metastatic PHEO (685/1296, 52.9%) and PGL (611/1296, 47.1%), diagnosed at a mean age of 43.9 ± 5.2 years. Mean follow-up was 6.3 ± 3.2 years. Of 532 patients with reported data, 40.4% had synchronous metastases. Five-year (7 studies, n = 738) and 10-year (2 studies, n = 55) mortality rates for patients with metastatic PPGL were 37% (95% CI, 24%-51%) and 29% (95% CI, 17%-42%), respectively. Higher mortality was associated with male sex (RR 1.50; 95% CI, 1.11-2.02) and synchronous metastases (RR 2.43; 95% CI, 1.01-5.85).
CONCLUSIONS
Available low-quality evidence from heterogeneous studies suggests low mortality rates of patients with metastatic PPGL. Male sex and synchronous metastases correlated with increased mortality. The outcomes of patients with metastatic PPGL have been inadequately assessed, indicating the need for carefully planned prospective studies.
Topics: Adrenal Gland Neoplasms; Adult; Female; Humans; Male; Middle Aged; Mortality; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Treatment Outcome
PubMed: 28746746
DOI: 10.1111/cen.13434 -
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 -
Minerva Endocrinologica Mar 2017Long-term outcome of patients with adrenal incidentaloma (AI) is unknown. The aim of this study was to systematically summarize the follow-up and outcome of clinically... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Long-term outcome of patients with adrenal incidentaloma (AI) is unknown. The aim of this study was to systematically summarize the follow-up and outcome of clinically silent AI who do not undergo surgery.
EVIDENCE ACQUISITION
All major databases and medical literature in English-language, published from 1998 to May 2015, were systematically searched for publications on AI. Primary endpoint was hormonal hyper function; secondary endpoints were time from diagnosis to study endpoint and the outcome of adrenalectomy. Meta-analysis was performed using both qualitative and quantitative approach.
EVIDENCE SYNTHESIS
A total of 11 publications were included. Total sample size was 1298 patients. Mean follow-up duration was 44.2 months. There were 82 patients confirmed to have subclinical Cushing's syndrome at diagnosis, with 1.79% new cases at the end of follow up (95% CI, 0.002 to 0.045). Incidence of Cushing's syndrome was 0.7% (95% CI, 0.001 to 0.013) and pheochromocytoma 0.4% (95% CI, 0.001 to 0.008). The mean tumor size was 2.52cm, with mean increment of 0.03cm to 2.9cm at the end of follow up. About 3% of patients ended up with surgery (95% CI, 0.01 to 0.05) but none were due to primary adrenal malignancy. Time of greatest risk of developing Cushing's syndrome and pheochromocytoma was between months 36 and 42 (hazard rate 14%), and between months 48 and 54 (hazard rate 7%) respectively.
CONCLUSIONS
Malignant change in non-functioning AI is rare. The risk of developing overt disease over the follow-up period is low. A less stringent imaging and functional work-up interval can be considered.
Topics: Adrenal Gland Neoplasms; Disease Progression; Humans; Treatment Outcome
PubMed: 26698544
DOI: 10.23736/S0391-1977.16.02394-4 -
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 -
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 -
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 -
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 -
Wideochirurgia I Inne Techniki... Mar 2022The application of robotic adrenalectomy (RA) has been increasing. However, there is still controversy about whether RA is more feasible than laparoscopic adrenalectomy...
INTRODUCTION
The application of robotic adrenalectomy (RA) has been increasing. However, there is still controversy about whether RA is more feasible than laparoscopic adrenalectomy (LA) for pheochromocytoma (PHEO).
AIM
To evaluate the efficacy and safety of RA vs. LA for PHEO.
MATERIAL AND METHODS
A literature search of the PubMed, Ovid, and Scopus databases was performed to identify eligible studies up to April 2021. All studies comparing RA versus LA for PHEO were included. Data were analysed using the Cochrane Collaboration's Review Manager (RevMan) 5.4 software.
RESULTS
Overall, 4 studies including 386 patients (RA 155; LA 231) were included. RA might have larger tumour size (WMD = 0.72 cm, 95% CI: 0.31 to 1.13; p < 0.001). There were no statistically significant differences in operative time (WMD = -12.49 min, 95% CI: -29.50 to 4.52; p = 0.15), estimated blood loss (EBL) (WMD = -28.48 ml, 95% CI: -58.92, 1.95; p = 0.07), transfusion rate (OR = 0.70, 95% CI: 0.07 to 7.07; p = 0.77), or conversion rate (OR = 0.44, 95% CI: 0.07 to 2.88; p = 0.39). There were no significant differences between the 2 groups in terms of postoperative complications (OR = 1.06, 95% CI: 0.62 to 1.82; p = 0.84) and Clavien Dindo score ≥ 3 complications (OR = 1.15, 95% CI: 0.39 to 3.41; p = 0.80). Patients from the RA group could benefit from shorter length of hospital stay (WMD = -0.51 days, 95% CI -0.91 to -0.12; p = 0.01).
CONCLUSIONS
RA is a feasible, safe, and comparable treatment option for PHEO.
PubMed: 35251386
DOI: 10.5114/wiitm.2021.107764