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Clinical Endocrinology Dec 2019Inoperable and metastatic pheochromocytomas and paragangliomas (PPGLs) present a therapeutic challenge with current treatment options being limited to radiolabelled... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Inoperable and metastatic pheochromocytomas and paragangliomas (PPGLs) present a therapeutic challenge with current treatment options being limited to radiolabelled meta-iodo-benzyl-guanidine (MIBG) and systemic chemotherapy. Peptide receptor radionuclide therapy (PRRT) seems to be a promising option for these patients with few studies reporting favourable response. This systematic review was conducted to evaluate the efficacy and safety of PRRT in patients with advanced PPGLs.
METHODS
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in PubMed, Scopus and Embase were made using relevant keywords and articles up to May 2019 were included. Data on efficacy and toxicity were extracted from the individual articles, and pooled estimates were generated using meta-analysis.
RESULTS
Twelve articles consisting of 201 patients with advanced PPGLs were included. Overall, treatment with PRRT achieved an objective response rate of 25% (95% CI: 19%-32%) and a disease control rate of 84% (95% CI: 77%-89%). Clinical and biochemical responses were seen in 61% and 64% of the patients, respectively. Among the PRRTs, similar tumour response rates were noted for Y-yttrium- and Lu-lutetium-based agents. Treatment-related adverse effects were minimal with grade 3/4 neutropenia, thrombocytopenia, lymphopenia and nephrotoxicity observed in 3%, 9%, 11% and 4% of the patients, respectively. Treatment discontinuation was noted in five out of 102 patients.
CONCLUSIONS
Peptide receptor radionuclide therapy is a safe and efficacious treatment option for advanced PPGLs and may be considered a viable alternative to chemotherapy and I- MIBG.
Topics: Female; Heterocyclic Compounds; Humans; Male; Octreotide; Organometallic Compounds; Paraganglioma; Peptides, Cyclic; Pheochromocytoma; Radiopharmaceuticals; Receptors, Peptide
PubMed: 31569282
DOI: 10.1111/cen.14106 -
World Journal of Urology Feb 2022Paraganglioma of the urinary bladder (UBPGL) is a rare neuroendocrine tumor diagnosed in many patients only after surgery. We, therefore, assessed clinical clues...
Differences in clinical presentation and management between pre- and postsurgical diagnoses of urinary bladder paraganglioma: is there clinical relevance? A systematic review.
PURPOSE
Paraganglioma of the urinary bladder (UBPGL) is a rare neuroendocrine tumor diagnosed in many patients only after surgery. We, therefore, assessed clinical clues relevant to presurgical diagnosis and clinical consequences in patients with a missed presurgical diagnosis of UBPGL.
MATERIALS AND METHODS
Case reports describing a UBPGL (published from 1-1-2001 and 31-12-2020) were identified in Pubmed. Two authors independently performed data extraction and assessed data quality according to the PRISMA guideline. Patients were divided into two groups: UBPGL diagnosis before and after surgery.
RESULTS
We included 177 articles reporting 194 cases. In 90 (46.4%) patients, the UBPGL was diagnosed before and in 104 (53.6%) after surgery. In presurgically diagnosed UBPGL, hypertension and catecholamine-associated symptoms were 2- to 3-fold (p < 0.001) more frequent than in postsurgically diagnosed patients whereas hematuria was twofold (p = 0.003) more prevalent in those with postsurgical diagnosis. Hypertension was an independent factor for presurgical biochemical testing (OR 4.45, 95% CI 1.66-11.94) while hematuria (OR 0.23, 95% CI 0.09-0.60) was an independent factor for not performing presurgical biochemical testing. Most patients diagnosed after surgery were not pretreated with alpha-adrenoceptor blockade (95.2%), underwent more frequently transurethral resection instead of cystectomy (70.2% vs. 23.1%) and had more frequent peroperative complications and residual tumor mass.
CONCLUSIONS
In nearly half of all patients with a UBPGL, the diagnosis was not established before surgery. Hypertension and hematuria contributed independently to a presurgical diagnosis. Postsurgical diagnosis, which was associated with suboptimal presurgical and surgical management, resulted in more peroperative complications and incomplete tumor resections.
Topics: Cystectomy; Hematuria; Humans; Paraganglioma; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 34655306
DOI: 10.1007/s00345-021-03851-x -
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 -
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 -
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 -
European Journal of Endocrinology Oct 2016To systematically review the incidence and factors associated with recurrences or new tumors after apparent complete resection of pheochromocytoma or... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To systematically review the incidence and factors associated with recurrences or new tumors after apparent complete resection of pheochromocytoma or thoraco-abdomino-pelvic paraganglioma.
DESIGN
A systematic review and meta-analysis of published literature was performed.
METHODS
Pubmed and Embase from 1980 to 2012 were searched for studies published in English on patients with non-metastatic pheochromocytoma or thoraco-abdomino-pelvic paraganglioma, complete tumor resection, postoperative follow-up exceeding 1 month, and recurrence or new tumor documented by pathology, hormonal dosages, or imaging tests. Incidence rates of new events after curative surgery were calculated for each study that had sufficient information and pooled using random-effect meta-analysis.
RESULTS
In total, 38 studies were selected from 3518 references, of which 36 reported retrospective cohorts from the USA, Europe, and Asia. Patient follow-up was neither standardized nor exhaustive in the included studies. A clear description of patient retrieval methods was available for nine studies and the follow-up protocol and patient flow for four studies. Only two studies used multivariable methods to assess potential predictors of postoperative events.The overall rate of recurrent disease from 34 studies was 0.98 events/100 person-years (95% confidence interval 0.71, 1.25). Syndromic diseases and paragangliomas were consistently associated with a higher risk of a new event in individual studies and in meta-regression analysis.
CONCLUSIONS
The risk of recurrent disease after complete resection of pheochromocytoma may be lower than that previously estimated, corresponding to five events for 100 patients followed up for 5 years after complete resection. Risk stratification is required to tailor the follow-up protocol after complete resection of a pheochromocytoma or paraganglioma. Large multicenter studies are needed to this end.
Topics: Adrenal Gland Neoplasms; Humans; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Paraganglioma; Pheochromocytoma
PubMed: 27080352
DOI: 10.1530/EJE-16-0189 -
Brain Sciences Sep 2022Staged surgery strategy was preferred for patients with intra-extracranial communicating jugular foramen paraganglioma (IECJFP). A female patient who presented mild...
Staged surgery strategy was preferred for patients with intra-extracranial communicating jugular foramen paraganglioma (IECJFP). A female patient who presented mild tinnitus, headache, and dizziness, together with preoperative related imaging, was diagnosed with a left intra-extracranial communicating jugular foramen lesion in November 2015 and accepted an initial operation for the intracranial tumor by retrosigmoid approach. The pathologic report was paraganglioma. In November 2021, a subtotal resection of the extracranial tumor was conducted for prominent lower cranial nerves (LCNs) deficit and middle ear involvement by infratemporal approach. In patients with IECJFP accompanied by LCNs deficit and middle ear involvement, an initial surgery for extracranial lesion and a second procedure for intracranial tumor were appropriate. However, the first operation for the intracranial lesion was preferred in IECJFP cases without LCNs deficit and middle ear involvement, as it could remove compression to the neurovascular structure and brain stem, clarify a pathological diagnosis, avoid a CSF leak, and prevent a severe neurological disorder from extracranial lesion excision. Subtotal resection of the extracranial tumor would be performed when lesion became larger combined with obvious LCNs disorder and tympanic cavity involvement. Consideration of specific staged surgical strategy for IECJFP in accordance with preoperative LCNs deficit and tympanic cavity involvement could prevent critical postoperative neurological deficit and improve quality of life in the long term.
PubMed: 36138993
DOI: 10.3390/brainsci12091257 -
Interventional Neuroradiology : Journal... Jul 2023Embolization of head and neck paragangliomas (HNPs) is a well-established treatment strategy and adjunctive therapy. However, the optimal mode of intervention, whether... (Review)
Review
INTRODUCTION
Embolization of head and neck paragangliomas (HNPs) is a well-established treatment strategy and adjunctive therapy. However, the optimal mode of intervention, whether by direct percutaneous puncture (DP) or via transarterial embolization (TAE), remains unclear.
METHODS
The aim of this study was to complete a systematic literature review and meta-analysis to compare the safety and efficacy of DP versus TAE for HNP embolization. The Cochrane Library and MEDLINE databases were used to identify studies describing the clinical outcomes of either DP or TAE for HNP embolization. Outcome measures included: complete angiographic devascularization, major complications, and minor complications. Pooled rates were calculated for each variable which were then compared with meta-regression using a random effects model.
RESULTS
Thirty-one retrospective studies met inclusion criteria, detailing 394 patients with 411 HNPs. Overall, DP was associated with a higher rate of complete devascularization (91.5%, 95% confidence interval [CI]: 85.6% to 97.4%; = 0%) when compared to TAE technique (40.1%, CI: 27.2% to 58.9%; = 93%). However, there was no difference regarding major complication rates between DP (6%, CI:1.3% to 10.8%; = 0%) and TAE for HNP embolization (3.3%, CI: 1.4% to 5.3%; = 0%) (p = 0.370), nor in minor complications between the techniques (p = 0.211). Subgroup analysis of TAE embolic agents revealed that particle embolics were associated with a significantly lower rate of major complications (2.5%; 0.4% to 4.6%; = 0%) when compared to liquid embolics (10.6%, CI:4% to 17.3%; = 48%; p = 0.022).
CONCLUSIONS
A DP approach for HNP embolization results in a higher rate of complete devascularization and with a similar complication profile when compared to TAE. These findings also suggest that particle embolics are associated with fewer major complications compared to liquid embolics when TAE is utilized.
PubMed: 37455341
DOI: 10.1177/15910199231188859 -
Head & Neck May 2023Pre-operative embolization prior to surgical resection of carotid body tumors was meant to decrease intraoperative blood loss and operative time. Yet, potential... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pre-operative embolization prior to surgical resection of carotid body tumors was meant to decrease intraoperative blood loss and operative time. Yet, potential confounders such as different Shamblin classes have never been analyzed. Aim of our meta-analysis was to investigate effectiveness of a pre-operative embolization according to different Shamblin classes.
METHODS
Five studies comprising 245 patients were included. A random effects model meta-analysis was conducted, and the I statistic was used to assessment for heterogeneity.
RESULTS
Pre-operative embolization was associated with a significant reduction in blood loss (WM: 276.4 mL; 95% CI, 201.9-378.3, p < 0.01); an absolute mean reduction, though not statistically significant, was observed in both Shamblin 2 and 3 classes. No difference in operative time was found between the two strategies (WM: 192.0 min; 95% CI, 157.7-234.1, p = 1.0).
CONCLUSIONS
Embolization proved an overall significant reduction in perioperative bleeding, which did not reach threshold for statistical significance when Shamblin classes were singularly considered.
Topics: Humans; Carotid Body Tumor; Vascular Surgical Procedures; Retrospective Studies; Embolization, Therapeutic; Blood Loss, Surgical; Treatment Outcome
PubMed: 36896854
DOI: 10.1002/hed.27318 -
Neurosurgical Review Feb 2022Cauda equina paragangliomas are rare benign extra-adrenal neuroendocrine tumours arising from the neural crest cells associated with autonomic ganglia. These tumours are... (Review)
Review
Cauda equina paragangliomas are rare benign extra-adrenal neuroendocrine tumours arising from the neural crest cells associated with autonomic ganglia. These tumours are often mistaken preoperatively for ependymomas or schwannomas. Patients present with axial or radicular pain with or without neurological deficits. Recurrence, secretory features and length of follow-up are controversial. We conducted a retrospective cohort study of paraganglioma through searching a prospectively maintained histopathology database. Patient demographics, presentation, surgery, complications, recurrence, follow-up and outcome between 2004 and 2016 were studied. The primary aim was to collate and describe the current evidence base for recurrence and secretory features of the tumour. The secondary objective was to report outcome and follow-up strategy. A scoping review was performed in accordance with the PRISMA-ScR Checklist. Ten patients were diagnosed (M:F 7:3) with a mean age of 53.6 ± 5.1 (range 34-71 years). MRI scans revealed intradural lumbar enhancing lesions. All patients had complete microsurgical excisions without adjuvant therapy with no recurrence with a mean follow-up of 5.1 ± 1.4 years. Tumours were attached to the filum terminale. Electron microscopic images demonstrated abundant neurosecretory granules with no evidence of catecholamine production. A total of 620 articles were screened and 65 papers (including ours) combining 121 patients (mean age 48.8 and M:F 71:50) were included. The mean follow-up was 3.48 ± 0.46 (range 0.15-23 years). Back pain was the most common symptom (94%). Cure following surgery was achieved in 93% of the patients whilst 7% had recurrence. Total resection likely results in cure without the need for adjuvant therapy or prolonged follow-up. However, in certain situations, the length of follow-up should be determined by the treating surgeon.
Topics: Adult; Aged; Cauda Equina; Ependymoma; Humans; Magnetic Resonance Imaging; Middle Aged; Paraganglioma; Peripheral Nervous System Neoplasms; Retrospective Studies
PubMed: 34021421
DOI: 10.1007/s10143-021-01565-7