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The Journal of Clinical Endocrinology... Apr 2024Carriers of germline pathogenic variants (PV) in succinate dehydrogenase type B (SDHB) are at increased risk of developing pheochromocytomas and paragangliomas (PPGL)....
CONTEXT
Carriers of germline pathogenic variants (PV) in succinate dehydrogenase type B (SDHB) are at increased risk of developing pheochromocytomas and paragangliomas (PPGL). Understanding their outcomes can guide recommendations for risk assessment and early detection.
OBJECTIVE
We performed a systematic review and meta-analysis of the following outcomes in SDHB PV carriers: age-specific risk of developing tumors, metastatic progression, second primary tumor development, and mortality.
MATERIALS AND METHODS
Pubmed, MEDLINE and EMBASE were searched. Sixteen studies met the inclusion criteria and were sorted into four outcome categories: age-specific penetrance, metastatic disease, risk of second tumour and mortality. We assessed heterogeneity and performed a meta-analysis across studies using a random effects model with the DerSimonian and Laird method.
RESULTS
Penetrance of PPGL for non-proband/non-index SDHB PV carriers by age 20 was 4% (95% CI, 3%-6%), 11% (95% CI, 8%-15%) by age 40, 24% (95% CI, 19%-31%) by age 60 and 35% (95% CI, 25%-47%) by age 80. The overall risk of metastatic disease for non-proband/non-index carriers with PPGL was 9% (95% CI, 5-16%) per lifetime. In all affected cases (combining both proband/index and non-proband/non-index carriers with tumors), the risk of a second tumor was 24% (95% CI, 18-31%) and all cause 5-year mortality was 18% (95% CI 6-40%).
CONCLUSION
Penetrance for PPGL in SDHB PV carriers increases linearly with age. Affected carriers are at risk of developing and dying from metastatic disease, or of developing second tumors. Lifelong surveillance is appropriate.
PubMed: 38605204
DOI: 10.1210/clinem/dgae233 -
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 -
The Journal of Clinical Endocrinology... Jan 2021Evidence on follow-up duration for patients with sporadic pheochromocytomas is absent, and current guidelines of the European Society of Endocrinology, American... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence on follow-up duration for patients with sporadic pheochromocytomas is absent, and current guidelines of the European Society of Endocrinology, American Association of Clinical Endocrinologists and Endocrine Surgeons, and the Endocrine Society are ambiguous about the appropriate duration of follow-up. The aim of this systematic review and meta-analysis is to evaluate the recurrence rate of sporadic pheochromocytomas after curative adrenalectomy.
MATERIALS AND METHODS
A literature search in PubMed, Embase, and the Cochrane Library was performed. A study was eligible if it included a clear report on the number of sporadic patients, recurrence rate, and follow-up duration. Studies with an inclusion period before 1990, <2 years of follow-up, <10 patients, and unclear data on the sporadic nature of pheochromocytomas were excluded. A meta-analysis on recurrence was performed provided that the heterogeneity was low (I2 < 25%) or intermediate (I2 26-75%). Hozo's method was used to calculate weighted mean follow-up duration and weighted time to recurrence with combined standard deviations (SDs).
RESULTS
A total of 13 studies, including 430 patients, were included in the synthesis. The meta-analysis results describe a pooled recurrence rate after curative surgery of 3% (95% confidence interval: 2-6%, I2 = 0%), with a weighted mean time to recurrence of 49.4 months (SD = 30.7) and a weighted mean follow-up period of 77.3 months (SD = 32.2).
CONCLUSIONS
This meta-analysis shows a very low recurrence rate of 3%. Prospective studies, including economical and health effects of limited follow-up strategies for patients with truly sporadic pheochromocytomas should be considered.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Humans; Neoplasm Recurrence, Local; Pheochromocytoma; Prognosis
PubMed: 33125073
DOI: 10.1210/clinem/dgaa794 -
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 -
European Journal of Surgical Oncology :... Jun 2020To evaluate the efficacy and safety of laparoscopic adrenalectomy (LA) vs open adrenalectomy (OA) for pheochromocytoma (PHEO). (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the efficacy and safety of laparoscopic adrenalectomy (LA) vs open adrenalectomy (OA) for pheochromocytoma (PHEO).
METHODS
A systematic literature research of PubMed, Ovid, Scopus, and citation lists were performed to identify eligible studies. All studies comparing LA versus OA for PHEO were included.
RESULTS
Overall, fourteen studies including 743 patients (LA 391; OA 352) were included. LA might have smaller tumor size (WMD -0.92 cm, 95% CI -1.09 to -0.76; p < 0.001) and higher body mass index (BMI) (WMD 0.31 kg/m, 95% CI 0.04 to 0.58; p = 0.02). Compared to OA, LA showed lower estimated blood loss (EBL) (WMD -207.72 ml, 95% CI -311.26, -104.19; p < 0.001), lower transfusion rate (OR 0.25, 95% CI 0.16 to 0.38; p < 0.001), lower hemodynamic instability (HI) (OR 0.61, 95% CI 0.42 to 0.88; p = 0.009), less postoperative complications (OR 0.55, 95% CI 0.34 to 0.89; p = 0.02), less Clavien Dindo score ≥3 complications (OR 0.51, 95% CI 0.27 to 0.97; p = 0.04), shorter return to diet time (WMD -0.76 days, 95% CI -1.27 to -0.25; p = 0.003), and shorter length of hospital stay (WMD -1.76 days, 95% CI -2.94 to -0.58; p < 0.001). The subgroup analysis of studies since 2008 showed consistent results.
CONCLUSION
LA shows a feasible, safe and superior treatment option for PHEO, because it provides superior perioperative and recovery outcomes without increasing complications.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Humans; Laparoscopy; Operative Time; Pheochromocytoma; Retroperitoneal Space
PubMed: 32102743
DOI: 10.1016/j.ejso.2020.02.009 -
Endocrine, Metabolic & Immune Disorders... 2021Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma...
BACKGROUND
Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and non-endocrine features. However, the diagnosis and treatment are usually delayed.
METHODS
This study reports 5 Chinese pedigrees with 5 individuals harboring germline RETM918T, and systematically reviewed previous Chinese literature reported.
RESULTS
All 5 patients initially presented MTC, but none had biochemically cured postoperatively. 2 also presented bilateral PHEO after adrenal-sparing surgery, 1 needed steroid replacement. Further, a total of 32 MEN 2B patients from literature were clustered with 28 available for analysis. 26 (92.8%) were diagnosed by endocrine-related symptoms; the remaining 2 (7.2%) due to RET testing and oral symptoms, respectively. 25 patients underwent thyroidectomy with/without neck lymph node dissection at the mean age of (23.3 ± 10.4) years. Histopathological examination revealed MTC (100%). Of them, 17 had definite TNM stage, with 1 in stage III and others in IV. Other information of MEN 2B-related symptoms included penetrance of PHEO (60.7%), constipation (32.1%), Hirschsprung disease (25%), alacrima (17.8%), mucosal ganglioneuroma (96.4%) and marfanoid habitus (71.4%). 19 patients were verified harboring RET-M918T (c.2753T>C), of whom 15 (78.9%) were de novo mutation. The other 9 were clinically diagnosed as MEN 2B.
DISCUSSION & CONCLUSION
The initial diagnosis of MEN 2B is relatively later, and diagnosed by non-endocrine components is extremely lower. Recognition of MEN 2B and its non-endocrine-related components is still the utmost requirement for a Chinese physician. Combined RET screening and serum calcitonin detection can facilitate early diagnosis.
Topics: Adolescent; Adult; Asian People; Biomarkers, Tumor; Calcitonin; Child; China; DNA Mutational Analysis; Early Detection of Cancer; Female; Genetic Predisposition to Disease; Heredity; Humans; Lymph Node Excision; Male; Middle Aged; Multiple Endocrine Neoplasia Type 2b; Mutation; Pedigree; Predictive Value of Tests; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Risk Factors; Thyroidectomy; Treatment Outcome; Young Adult
PubMed: 32914730
DOI: 10.2174/1871530320666200910112230 -
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 -
Mayo Clinic Proceedings Oct 2019To assess the diagnostic accuracy of unenhanced computed tomography (CT) attenuation values to exclude a pheochromocytoma in the diagnostic work-up of patients with an... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the diagnostic accuracy of unenhanced computed tomography (CT) attenuation values to exclude a pheochromocytoma in the diagnostic work-up of patients with an adrenal incidentaloma and to model the associated difference in diagnostic costs.
METHODS
The MEDLINE and Embase databases were searched from indexing to September 27, 2018, and studies reporting the proportion of pheochromocytomas on either side of the 10-Hounsfield unit (HU) threshold on unenhanced CT were included. The pooled proportion of pheochromocytomas with an attenuation value greater than 10 HU was determined, as were the modeled financial costs of the current and alternative diagnostic approaches.
RESULTS
Of 2957 studies identified, 31 were included (N=1167 pheochromocytomas). Overall risk of bias was low. Heterogeneity was not observed between studies (Q=11.5, P=.99, I=0%). The pooled proportion of patients with attenuation values greater than 10 HU was 0.990 (95% CI, 0.984-0.995). The modeled financial costs using the new diagnostic approach were €55 (∼$63) lower per patient.
CONCLUSION
Pheochromocytomas can be reliably ruled out in the case of an adrenal lesion with an unenhanced CT attenuation value of 10 HU or less. Therefore, determination of metanephrine levels can be restricted to adrenal tumors with an unenhanced CT attenuation value greater than 10 HU. Implementing this novel diagnostic strategy is cost-saving.
Topics: Adrenal Gland Neoplasms; Costs and Cost Analysis; Diagnosis, Differential; Humans; Incidental Findings; Pheochromocytoma; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 31515105
DOI: 10.1016/j.mayocp.2019.03.030 -
The British Journal of Surgery Jan 2020Preoperative α-blockade in phaeochromocytoma surgery is recommended by all guidelines to prevent intraoperative cardiocirculatory events. The aim of this meta-analysis... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Preoperative α-blockade in phaeochromocytoma surgery is recommended by all guidelines to prevent intraoperative cardiocirculatory events. The aim of this meta-analysis was to assess the benefit of such preoperative treatment compared with no treatment before adrenalectomy for phaeochromocytoma.
METHODS
A systematic literature search was undertaken in MEDLINE, Web of Science and CENTRAL without language restrictions. Randomized and non-randomized comparative studies investigating preoperative α-blockade in phaeochromocytoma surgery were included. Data on perioperative safety, effectiveness and outcomes were extracted. Pooled results were calculated as an odds ratio or mean difference with 95 per cent confidence interval.
RESULTS
A total of four retrospective comparative studies were included investigating 603 patients undergoing phaeochromocytoma surgery. Mortality, cardiovascular complications, mean maximal intraoperative systolic and diastolic BP, and mean maximal intraoperative heart rate did not differ between patients with or without α-blockade. The certainty of the evidence was very low owing to the inferior quality of studies.
CONCLUSION
This meta-analysis has shown a lack of evidence for preoperative α-blockade in surgery for phaeochromocytoma. RCTs are needed to evaluate whether preoperative α-blockade can be abandoned.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Adrenergic alpha-Antagonists; Cardiovascular Diseases; Humans; Pheochromocytoma; Preoperative Care
PubMed: 31903584
DOI: 10.1002/bjs.11348 -
Journal of Clinical Epidemiology May 2024The aim of this systematic review was to summarize national and international guidelines that made recommendations for monitoring patients diagnosed with low-risk...
OBJECTIVES
The aim of this systematic review was to summarize national and international guidelines that made recommendations for monitoring patients diagnosed with low-risk cancer. It appraised the quality of guidelines and determined whether the guidelines adequately identified patients for monitoring, specified which tests to use, defined monitoring intervals, and stated triggers for further intervention. It then assessed the evidence to support each recommendation.
STUDY DESIGN AND SETTING
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, we searched PubMed and Turning Research into Practice databases for national and international guidelines' that were written in English and developed or updated between 2012 and 2023. Quality of individual guidelines was assessed using the AGREE II tool.
RESULTS
Across the 41 published guidelines, 48 different recommendations were identified: 15 (31%) for prostate cancer, 11 (23%) for renal cancer, 6 (12.5%) for thyroid cancer, and 10 (21%) for blood cancer. The remaining 6 (12.5%) were for brain, gastrointestinal, oral cavity, bone and pheochromocytoma and paraganglioma cancer. When combining all guidelines, 48 (100%) stated which patients qualify for monitoring, 31 (65%) specified which tests to use, 25 (52%) provided recommendations for surveillance intervals, and 23 (48%) outlined triggers to initiate intervention. Across all cancer sites, there was a strong positive trend with higher levels of evidence being associated with an increased likelihood of a recommendation being specific (P = 0.001) and the evidence for intervals was based on expert opinion or other guidance.
CONCLUSION
With the exception of prostate cancer, the evidence base for monitoring low-risk cancer is weak and consequently recommendations in clinical guidelines are inconsistent. There is a lack of direct evidence to support monitoring recommendations in the literature making guideline developers reliant on expert opinion, alternative guidelines, or indirect or nonspecific evidence.
Topics: Humans; Practice Guidelines as Topic; Neoplasms; Male; Female
PubMed: 38360377
DOI: 10.1016/j.jclinepi.2024.111280