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Biomedicines Mar 2023We have performed a systematic review to evaluate the efficacy and safety of [Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive... (Review)
Review
Efficacy and Safety of [Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review.
BACKGROUND
We have performed a systematic review to evaluate the efficacy and safety of [Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive pheochromocytoma/paraganglioma (PPGL), thymic neuroendocrine tumor (NET), bronchial NET, unknown primary NET, or medullary thyroid carcinoma (MTC).
METHODS
Studies identified in PubMed from inception to 13 May 2021 must have assessed [Lu]Lu-DOTA-TATE as a single agent and reported outcome data for the specific NET types of interest.
RESULTS
Two independent reviewers performed the screening and data extraction, resulting in 16 publications: PPGL ( = 7), bronchial NETs ( = 6; one also included NETs of unknown origin), and MTC ( = 3). Overall, [Lu]Lu-DOTA-TATE offers encouraging antitumor activity (overall tumor response rates and disease control rates) across NET types. Safety was favorable with most adverse events mild to moderate in severity, transient, and consistent with those seen in patients with gastroenteropancreatic (GEP)-NETs.
CONCLUSIONS
[Lu]Lu-DOTA-TATE has been used effectively in clinical practice to treat NETs of non-GEP origin.
PubMed: 37189646
DOI: 10.3390/biomedicines11041024 -
Life (Basel, Switzerland) Feb 2023: Partial adrenalectomy (PA) is an alternative option to total adrenalectomy for the treatment of hereditary pheochromocytoma (PHEO) to preserve cortical function and... (Review)
Review
: Partial adrenalectomy (PA) is an alternative option to total adrenalectomy for the treatment of hereditary pheochromocytoma (PHEO) to preserve cortical function and avoid life-long steroid replacement. The aim of this review is to summarize current evidence in terms of clinical outcome, recurrence, and corticosteroid therapy implementation after PA for MEN2-PHEOs. : From a total of 931 adrenalectomies (1997-2022), 16 of the 194 patients who underwent surgical treatment of PHEO had MEN2 syndrome. There were six patients scheduled for PA. MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched for English studies from 1981 to 2022. : Among six patients who underwent PA for MEN2-related PHEO in our center, we reported two with bilateral synchronous disease and three with metachronous PHEOs. One recurrence was registered. Less than 20 mg/day Hydrocortison therapy was necessary in 50% of patients after bilateral procedures. Systematic review identified 83 PA for MEN2-PHEO. Bilateral synchronous PHEO, metachronous PHEO and disease recurrence were reported in 42%, 26%, and 4% of patients, respectively. Postoperative steroid implementation was necessary in 65% of patients who underwent bilateral procedures. : PA seems to be a safe and valuable option for the treatment of MEN2-related PHEOs, balancing the risk of disease recurrence with the need for corticosteroid therapy.
PubMed: 36836782
DOI: 10.3390/life13020425 -
BMC Surgery Jul 2020Surgical resection is the main treatment for pheochromocytoma (PHEO). Although open surgery (OS) has been shown to be safe and feasible, the safety and efficacy of... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Surgical resection is the main treatment for pheochromocytoma (PHEO). Although open surgery (OS) has been shown to be safe and feasible, the safety and efficacy of laparoscopic surgery (LS) for PHEO remain controversial due to the uncertain effects of pneumoperitoneum on haemodynamics and the complexity of the tumour itself. This study was performed to compare the treatment outcomes of OS with those of LS for patients with PHEO.
METHODS
A systematic search through November 11, 2019, was conducted. All studies comparing outcomes of LS and OS for PHEO were included according to eligibility criteria. This meta-analysis was conducted using Review Manager Software, version 5.3, and STATA software, version 12.0. The quality of the included studies was assessed using the Newcastle-Ottawa scale.
RESULTS
Fourteen studies involving 626 patients were included in this meta-analysis. LS was associated with lower rates of intraoperative haemodynamic instability (IHD) [odds ratio (OR) = 0.61, 95% CI: 0.37 to 1.00, P = 0.05], less intraoperative blood loss [weighted mean difference (WMD) = - 115.27 ml, 95% confidence interval (CI): - 128.54 to - 101.99, P < 0.00001], lower blood transfusion rates [OR = 0.33, 95% CI: 0.21 to 0.52, P < 0.00001], earlier ambulation (WMD = - 1.57 d, 95% CI: - 1.97 to - 1.16, P < 0.00001) and food intake (WMD = - 0.98 d, 95% CI: - 1.36 to - 0.59, P < 0.00001), shorter drainage tube indwelling time (WMD = - 0.51 d, 95% CI: - 0.96 to - 0.07, P = 0.02) and postoperative stay (WMD = - 3.17 d, 95% CI: - 4.76 to - 1.58, P < 0.0001), and lower overall complication rates (OR = 0.56, 95% CI: 0.35 to 0.88, P = 0.01). However, no significant differences in operative time, postoperative blood pressure control, rates of severe complications, postoperative hypotension or cardiovascular disease (CVD) were found between the two groups.
CONCLUSIONS
LS is safe and effective for PHEO resection. Compared with OS, LS caused less IHD, providing an equal chance to cure hypertension while also yielding a faster and better postoperative recovery.
Topics: Adrenal Gland Neoplasms; Humans; Laparoscopy; Laparotomy; Length of Stay; Operative Time; Pheochromocytoma; Retrospective Studies; Treatment Outcome
PubMed: 32711496
DOI: 10.1186/s12893-020-00824-6 -
Frontiers in Molecular Neuroscience 2022Alzheimer's disease (AD) is a common age-related neurodegenerative disease characterized by progressive cognitive decline and irreversible memory impairment. Currently,...
Alzheimer's disease (AD) is a common age-related neurodegenerative disease characterized by progressive cognitive decline and irreversible memory impairment. Currently, several studies have failed to fully elucidate AD's cellular and molecular mechanisms. For this purpose, research on related cellular models may propose potential predictive models for the drug development of AD. Therefore, many cells characterized by neuronal properties are widely used to mimic the pathological process of AD, such as PC12, SH-SY5Y, and N2a, especially the PC12 pheochromocytoma cell line. Thus, this review covers the most systematic essay that used PC12 cells to study AD. We depict the cellular source, culture condition, differentiation methods, transfection methods, drugs inducing AD, general approaches (evaluation methods and metrics), and cellular models used in parallel with PC12 cells.
PubMed: 36683856
DOI: 10.3389/fnmol.2022.1016559 -
Journal of Personalized Medicine Sep 2022Neuroendocrine neoplasms (NEN) originate from neuroendocrine cells ubiquitously spread throughout the body. Hypercalcemia associated with cancer is the most common... (Review)
Review
BACKGROUND
Neuroendocrine neoplasms (NEN) originate from neuroendocrine cells ubiquitously spread throughout the body. Hypercalcemia associated with cancer is the most common life-threatening metabolic disorder in patients with advanced stage cancer. Paraneoplastic hypercalcemia is more commonly associated with hematological malignancies, renal and breast carcinomas, and squamous cell carcinomas, but it has also been described in patients with well-differentiated NEN, where it often remains undiagnosed. Among its causes, systemic secretion of parathyroid hormone-related protein (PTHrP) and ectopic production of 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) may be considered paraneoplastic causes of hypercalcemia. In order to clarify the diagnostic work up of paraneoplastic hypercalcemia in patients with NEN, we perform a systematic review, which is lacking in the literature.
METHODS
We performed a data search using MEDLINE and SCOPUS including papers from 1961 to 2021. We selected articles on paraneoplastic hypercalcemia associated with well-differentiated NEN.
RESULTS
The search led to the selection of 78 publications for a total of 114 patients. Pooled data showed that the most frequent primary tumor site associated with paraneoplastic hypercalcemia was pancreatic NEN, followed by Pheochromocytoma. In most cases, paraneoplastic hypercalcemia was caused by PTHrP production and secretion. In more than two thirds of cases, paraneoplastic hypercalcemia was present at the time of NEN diagnosis and, in metachronous cases, was related to local recurrence, distant metastasis development, or tumor progression. In most patients, a combination of therapeutic approaches was employed, and reduction of the tumor burden was essential to control the paraneoplastic syndrome.
DISCUSSION
The onset of hypercalcemia associated with cancer in patients with well-differentiated NEN represents a major clinical challenge. The complex clinical and therapeutical management of paraneoplastic hypercalcemia implies the need for a multidisciplinary approach, aimed at controlling the clinical syndrome and tumor growth.
PubMed: 36294693
DOI: 10.3390/jpm12101553 -
European Journal of Heart Failure Mar 2022Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of...
AIMS
Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.
METHODS AND RESULTS
We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170 885 individuals aged ≥30 years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule-based phenotypes (ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)-based interventions for HF prevention (RCT-HF), and 6 for cardiovascular disease prevention, but not HF (RCT-CVD), and the remainder had no RCT-based preventive interventions (RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5 years prior to HF diagnosis, 44.3% had ≥4 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT-CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT-0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1 year varied across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs.
CONCLUSION
One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs.
Topics: Heart Failure; Humans; Hypertension; Myocardial Infarction; Prognosis; Risk Factors
PubMed: 34969173
DOI: 10.1002/ejhf.2417 -
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 -
Asian Pacific Journal of Cancer... Jun 2021In this study, we aimed to detect Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) frequency in paragangliomas and pheochromocytomas (PPGL) with...
Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) Immunohistochemistry in Pheochromocytoma, Head and Neck Paraganglioma, Thoraco-Abdomino-Pelvic Paragangliomas: Is It a Good Idea to Use in Routine Work?
BACKGROUND
In this study, we aimed to detect Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) frequency in paragangliomas and pheochromocytomas (PPGL) with immunohistochemistry; compare with Pheochromacytoma of the Adrenal Gland Scaled Score (PASS) classification and analyse the differences between pheochromocytoma (Pheo), head-neck paragangliomas (HNPGL) and thoraco-abdominal-pelvic paraganglioma (TAPPGL) sub-groups.
METHODS
A total 114 PPGL cases (73 HNPGL, 15 TAPPGL and 27 Pheo belonging to 112 cases) are included. Immunohistochemically, SDHB and Ki-67 are investigated and malignancy risks are determined by PASS classification. Results are assessed statistically with chi-square test and p <0,01 is considered significant.
RESULTS
SDHB mutations are observed in 20 of 114 (17.54 %) PPGL cases, 3 (11,12%) of which is Pheo, 12 (16,44) is HNPGL, and 5 (35,71%) is TAPPGL (P <0,02). While 15/82 (18,29%) cases with SDHB mutations do not have a malignancy potential according to PASS classification, 5/32 (15,63%) cases has (p=0,73). TAPPGL, HNPGL and Pheo sub-groups have a significant difference between SDHB expression (p <0,02), malignancy potential according to PASS classification (p <0,0001) and Ki-67 proliferation index (p <0,0001).
CONCLUSION
To identify patients for molecular pathological examination, routine application of SDHB immunohistochemistry to PPGL tumors are suggested especially in HNPGLs.
Topics: Head and Neck Neoplasms; Humans; Immunohistochemistry; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase; Thoracic Neoplasms
PubMed: 34181326
DOI: 10.31557/APJCP.2021.22.6.1721 -
Journal of Integrative Neuroscience Jun 2021Metastatic pheochromocytoma of the spine (MPS) represents an extremely rare and challenging entity. While retrospective studies and case series make the body of the...
Metastatic pheochromocytoma of the spine (MPS) represents an extremely rare and challenging entity. While retrospective studies and case series make the body of the current literature and case reports, no systematic reviews have been conducted so far. This systematic review aims to perform a systematic review of the literature on this topic to clarify the status of the art regarding the surgical management of MPS. A systematic review according to PRISMA criteria has been performed, including all studies written in English and involving human participants. 15 papers for a total of 44 patients were finally included in the analysis. The median follow-up was 26.6 months. The most common localization was the thoracic spine (54%). In 30 out of 44 patients (68%), preoperative medications were administered. Open surgery was performed as the first step in 37 cases (84%). Neoadjuvant treatments, including preoperative embolization were reported in 18 (41%) cases, while adjuvant treatments were administered in 23 (52%) patients. Among those patients who underwent primary aggressive tumor removal and instrumentation, 16 out of 25 patients (64%) showed stable disease with no progression at the final follow-up. However, the outcome was not reported in 14 patients. Gross total resection of the tumor and spinal reconstruction appear to offer good long-term outcomes in selected patients. Preoperative alpha-blockers and embolization appear to be useful to enhance hemodynamic stability, avoiding potential detrimental complications.
Topics: Adrenal Gland Neoplasms; Humans; Orthopedic Procedures; Pheochromocytoma; Spinal Neoplasms
PubMed: 34258952
DOI: 10.31083/j.jin2002053 -
Clinical Cardiology May 2020Innumerable physical stress factors including externally administered catecholamines, and pheochromocytomas and paragangliomas (PPGLs) have been reported to trigger... (Meta-Analysis)
Meta-Analysis
Clinical features, complications, and outcomes of exogenous and endogenous catecholamine-triggered Takotsubo syndrome: A systematic review and meta-analysis of 156 published cases.
Innumerable physical stress factors including externally administered catecholamines, and pheochromocytomas and paragangliomas (PPGLs) have been reported to trigger Takotsubo syndrome (TS). A systematic search of PubMed/MEDLINE identified 156 patients with catecholamine-induced TS up to December 2017. Data were compared within the catecholamine-induced TS cohort, but some comparisons were also done to a previously published large all-TS cohort (n = 1750). The mean age was 46.4 ± 16.4 years (72.3% women). The clinical presentation was dramatic with high complication rates in (68.2%, n = 103; multiple complications 34.6%, n = 54). The most common TS ballooning pattern was apical or mid-apical (45.2%, n = 69), followed by basal pattern (28.8%, n = 45), global pattern (16.0%, n = 25), mid-ventricular (8.3%, n = 13), focal (0.6%, n = 1), and unidentified pattern (1.9%, n = 3). There was an increase in the prevalence of apical sparing ballooning pattern compared to all-TS population (37.7% vs 18.3%, P < .00001). Higher complication rates were observed in TS with global ballooning pattern compared to apical ballooning pattern (23/25, 92% vs 38/65, 58.5%; P = .0022). Higher complication rates were observed in patients with age < 50 years than patients >50 years (73/92, 79.3% vs 29/56, 51.8%, P = 0.0009). Recurrence occurred exclusively in patients with PPGL-induced TS (18/107 patients, 16.8%). PPGL-induced TS was characterized by more global ballooning's pattern (22/104, 21.2% vs 3/49, 6.1%, P = 0.02), and lower left ventricular ejection fraction (25.54 ± 11.3 vs 31.82 ± 9.93, P = 0.0072) compared to exogenous catecholamine-induced TS. In conclusion, catecholamine-induced TS was characterized by a dramatic clinical presentation with extensive left ventricular dysfunction, and high complication rate.
Topics: Adult; Aged; Biomarkers; Catecholamines; Female; Humans; Male; Middle Aged; Norepinephrine; Phenylephrine; Stroke Volume; Takotsubo Cardiomyopathy; Ventricular Function, Left
PubMed: 32125009
DOI: 10.1002/clc.23352