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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 -
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 -
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 -
International Journal of Surgery... Sep 2022To compare the safety and effectiveness of robot-assisted adrenalectomy (RA) and laparoscopic adrenalectomy (LA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the safety and effectiveness of robot-assisted adrenalectomy (RA) and laparoscopic adrenalectomy (LA).
METHODS
We performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the Methodological Quality of Systematic Reviews) Guidelines. Five databases, including Medline, PubMed, Cochrane Library, Scopus, and Web of Science, were systematically searched. The search timeframe was set from the creation of the database to December 2021.
RESULTS
There were 26 studies including 2985 patients. Our study found that the robotic technique was superior to conventional laparoscopy for estimated blood loss (WMD = -18.25, 95% CI [-27.85, -8.65], P < 0.01), length of stay (WMD = -0.45, 95% CI [-0.57, -0.33], P < 0.01), and conversion to open (OR = 0.31, 95% CI [0.12, 0.78], P = 0.01), while complications and readmissions were comparable. Interestingly, there was no difference in operative time between the two surgical modalities, but subgroup analysis found that the retroperitoneal route robotic technique took longer (WMD = 14.64, 95% CI [0.04, 29.24], P < 0.05), whereas the study of the mixed surgical modality (RA versus LA with mixed transabdominal and retroperitoneal surgical routes) found that the robot required less time (WMD = -12.29, 95% CI [-22.86, -1.72], P < 0.05). For pheochromocytoma, RA was superior to LA in terms of length of stay (WMD = -0.49, 95% CI [-0.83, -0.15], P < 0.01), with no difference in other indicators.
CONCLUSION
robotic-assisted adrenalectomy is a superior technique to conventional laparoscopy in managing adrenal tumors, even in the case of a specific adrenal tumor - pheochromocytoma.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Humans; Laparoscopy; Length of Stay; Operative Time; Pheochromocytoma; Robotic Surgical Procedures; Treatment Outcome
PubMed: 36075556
DOI: 10.1016/j.ijsu.2022.106853 -
Anticancer Research Sep 2022Pheochromocytomas (PHEOs) are a rare entity in the common population but have higher prevalence in neurofibromatosis type I (NFI) patients. In combination with pregnancy...
BACKGROUND/AIM
Pheochromocytomas (PHEOs) are a rare entity in the common population but have higher prevalence in neurofibromatosis type I (NFI) patients. In combination with pregnancy there are several reports on perioperative complications due to endocrine tumor activity; however, case reports on the malignant course of the disease could not be identified.
CASE REPORT
We report the case of a pregnant female patient with diagnosed NF1, who was referred to our hospital with metastatic PHEO. Because of worsening state, emergency cesarian section was performed at 33 weeks gestation and the patient required CPR and avECMO. Diagnostic workup showed a tumor of the right adrenal gland infiltrating the liver continuously, as well as the right kidney and vena cava inferior, and multiple disseminated bone metastases.
CONCLUSION
As NF1 patients seem to have a significantly higher risk for PHEO, routine testing before or during pregnancy needs to be discussed, as perioperative adverse events due to endocrine activity are common. In case of malignant PHEO, guidelines for surgical management of metastasis are still missing. As our case shows however, interdisciplinary management and constant readaptation of therapy regimen according to disease progress are important.
Topics: Female; Humans; Pregnancy; Adrenal Gland Neoplasms; Adrenal Glands; Neurofibromatosis 1; Pheochromocytoma
PubMed: 36039448
DOI: 10.21873/anticanres.15969 -
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 -
International Journal of Surgery... Aug 2022This systematic review and meta-analysis compared the safety and effectiveness of minimally invasive adrenalectomy (MIA) with open adrenalectomy (OA) in patients with... (Meta-Analysis)
Meta-Analysis Review
Safety and effectiveness of minimally invasive adrenalectomy versus open adrenalectomy in patients with large adrenal tumors (≥5 cm): A meta-analysis and systematic review.
BACKGROUND
This systematic review and meta-analysis compared the safety and effectiveness of minimally invasive adrenalectomy (MIA) with open adrenalectomy (OA) in patients with large adrenal tumors (≥5 cm).
MATERIALS AND METHODS
We performed a systematic review and cumulative meta-analysis of the primary outcomes according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. Five databases including Medline, PubMed, Cochrane Library, Scopus, and Web of Science were systematically searched. The time frame of the search was set from the creation of the database to March 2022.
RESULTS
Ten studies including 898 patients were included. Compared to OA, MIA is superior for length of stay [LOS WMD = -3.52, 95% CI (-4.61, -2.43), P < 0.01], drainage time [DT WMD = -0.68, 95% CI (-1.27, -0.09), P < 0.05] and fasting time [FT WMD = -0.95, 95% CI (-1.35, -0.55), P < 0.01], estimated blood loss [EBL WMD = -314.22, 95% CI (-494.76, -133.69), P < 0.01] and transfusion [WMD = -416.73, 95% CI (-703.75, -129.72), P < 0.01], while operative time (OT) and complications are not statistically different. For pheochromocytoma, MIA remains superior for LOS [WMD = -3.10, 95% CI (-4.61, -1.60), P < 0.01] and EBL [WMD = -273.65, 95% CI (-457.44, -89.86), P < 0.01], while OT and complications are not significantly different.
CONCLUSION
MIA offers advantages over OA in the management of large adrenal tumors, including in the case of a specific large adrenal tumor - large pheochromocytoma.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Humans; Laparoscopy; Length of Stay; Operative Time; Pheochromocytoma; Treatment Outcome
PubMed: 35870758
DOI: 10.1016/j.ijsu.2022.106779 -
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 -
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 -
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