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Langenbeck's Archives of Surgery Mar 2022Composite phaeochromocytoma is a tumour containing a separate tumour of neuronal origin in addition to a chromaffin cell tumour. This study reports on two cases from a... (Review)
Review
INTRODUCTION
Composite phaeochromocytoma is a tumour containing a separate tumour of neuronal origin in addition to a chromaffin cell tumour. This study reports on two cases from a single centre's records and presents a systematic literature review of composite phaeochromocytomas.
METHODS
In addition to describing 2 case reports, a systematic search of the Medline database from inception up to April 2020 was done for human case reports on composite phaeochromocytomas. Relevant titles and/or abstracts were screened, and full texts were reviewed to identify appropriate studies. Data was extracted and a descriptive analysis of presentation, clinical features, management strategies and outcomes was performed. The quality of included studies was assessed using a critical appraisal checklist.
RESULTS
There were 62 studies included, with a total of 94 patients. Of 91 patients where data was available, the median (range) age of patients was 48 (4-86) years. Of 90 patients where information was provided, 57% were female. In at least 28% of patients, a genetic cause was identified. Common presenting features include abdominal pain, palpable mass, cardiovascular and gastrointestinal symptoms. The most common tumour component with phaeochromocytoma is ganglioneuroma; other components include ganglioneuroblastoma, neuroblastoma and malignant peripheral nerve sheath tumours. In patients with follow-up data (n=48), 85% of patients were alive and well at a median (range) follow-up time of 18 (0.5-168) months.
CONCLUSION
Composite phaeochromocytoma is a rare tumour, with a significant genetic predisposition. This review summarises available epidemiological data, which will be useful for clinicians managing this rare condition.
Topics: Adrenal Gland Neoplasms; Aged; Aged, 80 and over; Brain Neoplasms; Female; Humans; Middle Aged; Pheochromocytoma
PubMed: 33651160
DOI: 10.1007/s00423-021-02129-5 -
Journal of the Endocrine Society Sep 2022Pheochromocytomas and paragangliomas (PPGLs) are known to be rare. However, there is scant literature reporting their epidemiology, particularly whether the diagnosis of...
CONTEXT
Pheochromocytomas and paragangliomas (PPGLs) are known to be rare. However, there is scant literature reporting their epidemiology, particularly whether the diagnosis of PPGL has increased with advances in medical imaging and biochemical and genetic testing.
OBJECTIVE
The primary objective of this systematic review was to determine the annual incidence of PPGLs and change over time.
DESIGN
A systematic review was performed. Medline, Embase, PubMed, and Web of Science Core Collection databases were searched to identify studies reporting PPGL incidence. Studies were eligible for inclusion from the database's inception until August 30, 2021.
RESULTS
A total of 6109 manuscripts were identified; 2282 duplicates were excluded, and a further 3815 papers were excluded after abstract and/or full text review. Twelve studies were included in the final review. The incidence of PPGL ranged from 0.04 to 0.95 cases per 100 000 per year. Incidence increased over time, from approximately 0.2/100,000 individuals in studies performed before 2000, to approximately 0.6/100,000 in studies undertaken after 2010. The mode of diagnosis changed over the same time period, with more patients diagnosed from incidental imaging findings, and fewer at autopsy or from symptoms.
CONCLUSION
The annual incidence of PPGL has increased over time. Much of this increase is likely from incidental identification of tumors on imaging. However, the epidemiology of PPGL remains understudied, in particular, in associations with altitude, ethnicity, and genetics. To improve early detection and management guidelines, these gaps should be addressed.
PubMed: 35919261
DOI: 10.1210/jendso/bvac105 -
Therapeutic Advances in Medical Oncology 2022Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been... (Review)
Review
BACKGROUND
Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been investigated for the treatment of other cancers. With the available evidence and the real-world performance of cabozantinib compared with clinical trial data, we performed a systematic review of cabozantinib monotherapy as treatment for solid tumors in adults.
METHODS
This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with PROSPERO (CRD42020144680). We searched for clinical and observational studies of cabozantinib monotherapy for solid tumors using Embase, MEDLINE, and Cochrane databases (October 2020), and screened relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Small studies ( < 25) and studies of cabozantinib combination therapies were excluded. Quality was assessed using National Institute for Health and Care Excellence methodology, and study characteristics were described qualitatively.
RESULTS
Of 2888 citations, 114 were included (52 randomized studies, 29 observational studies, 32 nonrandomized phase I or II studies or pilot trials, and 1 analysis of data from a randomized study and a nonrandomized study). Beyond approved indications, other tumors studied were castration-resistant prostate cancer, urothelial carcinoma, Ewing sarcoma, osteosarcoma, uveal melanoma, non-small-cell lung cancer, Merkel cell carcinoma, glioblastoma, pheochromocytomas and paragangliomas, cholangiocarcinoma, gastrointestinal stromal tumor, colorectal cancer, salivary gland cancer, carcinoid and pancreatic neuroendocrine tumors, and breast, endometrial and ovarian cancers. The most common adverse events were hypertension, diarrhea, and fatigue.
CONCLUSION
The identified evidence demonstrates the positive efficacy/effectiveness of cabozantinib monotherapy in various solid tumor types, with safety findings being consistent with those observed with other VEGFR-targeting tyrosine kinase inhibitors. When available, real-world findings were consistent with the data reported from clinical trials. A limitation of this review is the high proportion of abstracts; however, this allowed us to capture the most up-to-date findings.
PubMed: 35847482
DOI: 10.1177/17588359221107112 -
Frontiers in Endocrinology 2022Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is...
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is based on clinical suspicion, biochemical testing, imaging and histopathological confirmation. Increasingly widespread use of imaging studies and surveillance of patients at risk of PPGL due to a hereditary background or a previous tumor is leading to the diagnosis of these tumors at an early stage. This has resulted in an increasing use of the term "silent" PPGL. This term and other variants are now commonly found in the literature without any clear or unified definition. Among the various terms, "clinically silent" is often used to describe the lack of signs and symptoms associated with catecholamine excess. Confusion arises when these and other terms are used to define the tumors according to their ability to synthesize and/or release catecholamines in relation to biochemical test results. In such cases the term "silent" and other variants are often inappropriately and misleadingly used. In the present analysis we provide an overview of the literature and propose standardized terminology in an attempt at harmonization to facilitate scientific communication.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms; Catecholamines
PubMed: 36325453
DOI: 10.3389/fendo.2022.1021420 -
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 -
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 -
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 -
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 -
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 -
The Lancet. Diabetes & Endocrinology Jan 2021Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We...
BACKGROUND
Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy.
METHODS
We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression.
FINDINGS
The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery).
INTERPRETATION
Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes.
FUNDING
US National Institutes of Health.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Cohort Studies; Female; Fetal Diseases; Humans; Incidence; Infant, Newborn; Infant, Newborn, Diseases; Male; Middle Aged; Pheochromocytoma; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Retrospective Studies; Young Adult
PubMed: 33248478
DOI: 10.1016/S2213-8587(20)30363-6