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Cancers Feb 2019Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGLs, are neuroendocrine tumors of the adrenal medulla and paraganglia,... (Review)
Review
The Value of Histological Algorithms to Predict the Malignancy Potential of Pheochromocytomas and Abdominal Paragangliomas-A Meta-Analysis and Systematic Review of the Literature.
Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGLs, are neuroendocrine tumors of the adrenal medulla and paraganglia, respectively. These tumors exhibit malignant potential but seldom display evidence of metastatic spread, the latter being the only widely accepted evidence of malignancy. To counter this, pre-defined histological algorithms have been suggested to stratify the risk of malignancy: Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP). The PASS algorithm was originally intended for PCCs whereas the GAPP model is proposed for stratification of both PCCs and PGLs. In parallel, advances in terms of coupling overtly malignant PPGLs to the underlying molecular genetics have been made, but there is yet no combined risk stratification model based on histology and the overall mutational profile of the tumor. In this review, we systematically meta-analyzed previously reported cohorts using the PASS and GAPP algorithms and acknowledge a "rule-out" way of approaching these stratification models rather than a classical "rule-in" strategy. Moreover, the current genetic panorama regarding possible molecular adjunct markers for PPGL malignancy is reviewed. A combined histological and genetic approach will be needed to fully elucidate the malignant potential of these tumors.
PubMed: 30769931
DOI: 10.3390/cancers11020225 -
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 -
Journal of Nuclear Medicine : Official... Mar 2019We performed a systematic review and metaanalysis of the performance of Ga-DOTA-conjugated somatostatin receptor-targeting peptide (Ga-DOTA-SST) PET in the detection of... (Meta-Analysis)
Meta-Analysis
We performed a systematic review and metaanalysis of the performance of Ga-DOTA-conjugated somatostatin receptor-targeting peptide (Ga-DOTA-SST) PET in the detection of pheochromocytomas and paragangliomas (PPGLs). PubMed and Embase were searched until May 8, 2018. We included studies that reported the detection rate of Ga-DOTA-SST PET in patients with PPGLs. Detection rates were pooled using a random-effects model. Subgroup analyses and metaregression were performed to explore the cause of heterogeneity. Thirteen studies were included for qualitative synthesis. Per-lesion detection rates of Ga-DOTA-SST PET were consistently higher (ranging from 92% to 100%) than other imaging modalities, including F-fluorohydroxyphenylalanine (F-FDOPA) PET, F-FDG PET, and I-metaiodobenzylguanidine (I-MIBG) scintigraphy. However, in patients with polycythemia/paraganglioma syndrome, the detection rate of Ga-DOTA-DOTATATE PET was 35%. Nine studies (215 patients) with no specific inclusion criteria for subtype were quantitatively synthesized. The pooled detection rate was 93% (95% confidence interval [CI], 91%-95%), which was significantly higher than that of F-FDOPA PET (80% [95% CI, 69%-88%]), F-FDG PET (74% [95% CI, 46%-91%]), and I-MIBG scan (38% [95% CI, 20%-59%], < 0.001 for all). A greater prevalence of head and neck paragangliomas was associated with higher detection rates of Ga-DOTA-SST PET ( = 0.0002). Ga-DOTA-SST PET exhibited superior performance for lesion detection, over other functional imaging modalities, in patients with PPGLs, with the exception of polycythemia/paraganglioma syndrome. This might suggest Ga-DOTA-SST PET as a first-line imaging modality for the primary staging of PPGL or the restaging of PPGL with unknown genetic status.
Topics: Adrenal Gland Neoplasms; Gallium Radioisotopes; Heterocyclic Compounds, 1-Ring; Humans; Paraganglioma; Peptides; Pheochromocytoma; Receptors, Somatostatin
PubMed: 30030341
DOI: 10.2967/jnumed.118.211706 -
Journal of Neurological Surgery. Part... Aug 2018The purpose of this study was to perform a systematic review of the literature on orbital paragangliomas, evaluating clinical presentation, diagnosis, management...
The purpose of this study was to perform a systematic review of the literature on orbital paragangliomas, evaluating clinical presentation, diagnosis, management patterns, and prognosis. The systematic review was conducted based on the principles described in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. PubMed, Cochrane databases, Embase, and Web of Science were searched for articles related to orbital paragangliomas. Inclusion criteria included English language articles with original reports on human subjects. Data on clinical presentation, diagnosis, treatment, and prognosis were collected. Twenty-seven articles met inclusion criteria (28 total patients). The mean patient age was 37.1 years (range, 3-75 years); 13 (46.4%) patients were male. The most common presenting symptoms were proptosis (89.2%), visual acuity changes (67.9%), and extraocular muscle restriction (64.2%). Lesions were most commonly intraconal (92.9%). Single modality therapy was employed in 19 patients (67.9%), including excision in 12 patients (42.9%) and exenteration in 5 patients (17.9%). Ten patients (35.7%) developed recurrence, and there was a 92.9% survival rate (mean follow-up, 29 months). Orbital paragangliomas are rare tumors with an excellent prognosis. These lesions commonly present with proptosis, and are primarily managed surgically with simple excision, although exenteration and adjuvant radiation may be necessary for invasive tumors. This series is the largest and most comprehensive systematic review of orbital paragangliomas conducted to date.
PubMed: 30009123
DOI: 10.1055/s-0037-1615750 -
Journal of Clinical Hypertension... Mar 2018
Topics: Adipose Tissue, Brown; Adrenal Gland Neoplasms; Age Factors; Catecholamines; Female; Fluorodeoxyglucose F18; Humans; Male; Pheochromocytoma; Positron Emission Tomography Computed Tomography
PubMed: 29443440
DOI: 10.1111/jch.13228 -
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 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 -
European Annals of Otorhinolaryngology,... Sep 2017To review the optimal techniques for localization and characterization of neck paragangliomas (PGL). (Review)
Review
OBJECTIVE
To review the optimal techniques for localization and characterization of neck paragangliomas (PGL).
MATERIAL AND METHODS
Systematic review of the literature from the PubMed/Medline database.
RESULTS
Neck PGL are hypervascular tumours essentially arising from paraganglionic tissue situated at the carotid bifurcation (carotid body) and along the vagus nerve. Morphological and functional imaging are indicated to confirm the diagnosis, identify multifocal disease and for local and regional staging. MR angiography is the noninvasive technique of choice. CT scan and especially CT angiography are excellent alternatives for diagnosis and staging. Conventional arteriography remains useful preoperatively for embolization and occlusion tests. Functional imaging allows localization and characterization of PGLs. Somatostatin receptor scintigraphy (SRS) was the reference imaging technique for staging of sporadic PGLs. The indications for PET imaging have been extended over recent years in parallel with the development of new tracers such as [F]-FDOPA PET or Gallium-labelled DOTA peptides. Gallium-labelled DOTA peptides has become the first-line imaging modality in the evaluation of cervical PGLs, regardless of the genetic background.
CONCLUSION
Morphological and functional imaging is essential for the staging of neck PGL.
Topics: Computed Tomography Angiography; Head and Neck Neoplasms; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Neoplasm Staging; Paraganglioma; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 27887852
DOI: 10.1016/j.anorl.2016.10.003 -
The Oncologist Jul 2016Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs).... (Review)
Review
BACKGROUND
Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs.
PATIENTS AND METHODS
A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary.
RESULTS
The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9 months. The median time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation.
CONCLUSION
Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated. The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic.
IMPLICATIONS FOR PRACTICE
The present study reviewed all the available published data concerning the use of everolimus in 456 extrapancreatic neuroendocrine tumors (NETs) and summarized the current knowledge on the efficacy and safety of this drug, not yet approved except for pancreatic NETs. The progression-free survival rates and some objective responses seem promising and support the extension of the use of this drug. The site-by-site analysis seems to suggest that some subtypes of NETs, such as colorectal, could be more sensitive to everolimus than other primary NETs. No severe adverse events were usually reported and discontinuation was rarely required; thus, everolimus should be considered a valid therapeutic option for extrapancreatic NETs.
Topics: Adrenal Gland Neoplasms; Antineoplastic Agents; Carcinoma, Neuroendocrine; Colorectal Neoplasms; Disease-Free Survival; Everolimus; Humans; Ileal Neoplasms; Lung Neoplasms; Neuroendocrine Tumors; Pheochromocytoma; Stomach Neoplasms; Thyroid Neoplasms
PubMed: 27053503
DOI: 10.1634/theoncologist.2015-0420 -
Minerva Urologica E Nefrologica = the... Apr 2016Non-urothelial bladder cancer patients represent a rare and challenging group. Advances in bladder cancer to date have largely been driven by studies investigating... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Non-urothelial bladder cancer patients represent a rare and challenging group. Advances in bladder cancer to date have largely been driven by studies investigating common urothelial bladder tumors. New evidence is emerging supporting lymphadenectomy in standard surgical management of muscle invasive bladder cancer. We aim to explore the utility of lymphadenectomy in non-urothelial bladder cancer.
EVIDENCE ACQUISITION
A systematic review of the available peer-reviewed literature on PubMed was performed using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) search strategy. Tumors included in our analysis were squamous cell carcinomas, adenocarcinomas, paragangliomas, melanomas and sarcomas.
EVIDENCE SYNTHESIS
Our search strategy identified 8168 unique records and we included 135 full text articles in our final qualitative analysis. No comparative studies comparing lymphadenectomy outcomes in non-urothelial bladder tumors were identified. Practice of lymphadenectomy in combination with partial or radical cystectomy in the treatment of non-urothelial bladder cancer is relatively common. Pelvic recurrence following radical or partial cystectomy of non-urothelial tumors was more commonly reported in non-lymphadenectomy cohorts. The exception to this observation was the adenocarcinoma cohort.
CONCLUSIONS
Current evidence supporting lymphadenectomy in the surgical management of bladder cancer is largely based on studies limited to urothelial cancer. Despite this, the practice of lymphadenectomy in non-urothelial cancer is common. We support lymphadenectomy in non-urothelial bladder cancer given the minimal risk associated with the procedure and the potential for improved survival.
Topics: Combined Modality Therapy; Cystectomy; Humans; Lymph Node Excision; Urinary Bladder Neoplasms
PubMed: 26684181
DOI: No ID Found