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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 -
International Journal of Radiation... May 2020To perform a systematic review and pooled meta-analysis of adrenal metastasis stereotactic body radiation therapy (SBRT) outcomes, treatment characteristics, and... (Meta-Analysis)
Meta-Analysis
PURPOSE
To perform a systematic review and pooled meta-analysis of adrenal metastasis stereotactic body radiation therapy (SBRT) outcomes, treatment characteristics, and toxicity to define the efficacy and propose guidelines for intervention.
METHODS AND MATERIALS
We performed a comprehensive literature search of the Embase and PubMed databases of studies reporting outcome or toxicity data for photon-based SBRT of adrenal metastases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We then conducted a meta-analysis to estimate pooled overall response, local control (LC), and overall survival and analyzed these outcomes in the context of dosimetric parameters and toxicity using metaregression.
RESULTS
Thirty-nine studies published between 2009 and 2019 reporting outcomes on 1006 patients were included. The median follow-up was 12 months, and the median biological equivalent dose (BED10, alpha/beta = 10) was 67 Gy. The pooled overall response was 54.6% (95% confidence interval [CI], 46.5%-62.5%). The pooled 1- and 2-year rates of LC were 82% (95% CI, 74%-88%) and 63% (95% CI, 50%-74%), respectively, and the pooled 1- and 2-year overall survival rates were 66% (95% CI, 57%-74%) and 42% (95% CI, 31%-53%), respectively. There was a strong positive association between SBRT dose and 1- and 2-year LC (P < .0001, P = .0002) and an association with 2-year OS (P = .03). Based on a metaregression of dose and LC, BED10 of 60 Gy, 80 Gy, and 100 Gy predicted 1-year LC of 70.5%, 84.8%, and 92.9% and 2-year LC of 47.8%, 70.1%, and 85.6%, respectively. The overall rate of grade 3 or higher toxicity was 1.8%.
CONCLUSIONS
SBRT of adrenal metastases provides good 1-year LC with an excellent safety profile, and dose escalation may be associated with improved LC. Prospective studies are needed to validate these findings and determine whether there are subsets of patients for whom adrenal metastasis-directed SBRT may confer a survival advantage.
Topics: Adrenal Gland Neoplasms; Humans; Patient Reported Outcome Measures; Radiosurgery; Safety
PubMed: 32001383
DOI: 10.1016/j.ijrobp.2020.01.017 -
Frontiers in Endocrinology 2023Adult pure androgen-secreting adrenal tumors (PASATs) are extremely rare, and their characteristics are largely unknown.
BACKGROUND
Adult pure androgen-secreting adrenal tumors (PASATs) are extremely rare, and their characteristics are largely unknown.
METHODS
A rare case of adult bilateral PASATs was reported, and a systematic literature review of adult PASATs was conducted to summarize the characteristics of PASATs.
RESULTS
In total, 48 studies, including 40 case reports and 8 articles, were identified in this review. Analysis based on data of 42 patients (including current case and 41 patients from 40 case reports) showed that average age was 40.48 ± 15.80 years (range of 18-76). The incidence of adult PASAT peaked at 21-30 years old, while that of malignant PASAT peaked at 41-50 years old. Most PASAT patients were female (40/42, 95.23%), and hirsutism was the most common symptom (37/39, 94.87%). Testosterone (T) was the most commonly elevated androgen (36/42, 85.71%), and 26 of 32 tested patients presented increased dehydroepiandrosterone sulfate (DS) levels. In malignancy cases, disease duration was significantly decreased (1.96 vs. 4.51 years, P=0.025), and tumor diameter was significantly increased (8.9 vs. 4.9 cm, p=0.011). Moreover, the androgen levels, namely, T/upper normal range limit (UNRL) (11.94 vs. 4.943, P=0.770) and DS/UNRL (16.5 vs. 5.28, P=0.625), were higher in patients with malignancy. In total, 5 out of 7 patients showed an increase in DS or T in the human chorionic gonadotropin (HCG) stimulation test. Overall, 41 out of 42 patients (including current case) underwent adrenal surgery, and recurrence, metastasis, or death was reported in 5 out of 11 malignant patients even with adjuvant or rescue mitotane chemotherapy.
CONCLUSION
Adult PASAT, which is predominant in women, is characterized by virilism and menstrual dysfunction, especially hirsutism. Elevated T and DS may contribute to the diagnosis of adult PASAT, and HCG stimulation test might also be of help in diagnosis. Patients with malignant PASAT have a shorter disease duration, larger tumor sizes and relatively higher androgen levels. Surgery is recommended for all local PASATs, and Malignancy of PASAT should be fully considered due to the high risk of malignancy, poor prognosis and limited effective approaches.
Topics: Adult; Humans; Female; Adolescent; Young Adult; Middle Aged; Aged; Male; Androgens; Hirsutism; Adrenal Gland Neoplasms; Testosterone; Virilism
PubMed: 37033242
DOI: 10.3389/fendo.2023.1138114 -
Journal of Otolaryngology - Head & Neck... Jun 2015Immunoglobulin G4 related disease (IgG4-RD) is a poorly understood chronic inflammatory disorder affecting the middle-aged and elderly that can present to the... (Review)
Review
BACKGROUND
Immunoglobulin G4 related disease (IgG4-RD) is a poorly understood chronic inflammatory disorder affecting the middle-aged and elderly that can present to the otolaryngologist. We aim to summarize the current literature regarding the manifestations and management of IgG4-RD in the head and neck.
METHODS
Pubmed and EMBASE were searched using the term relevant search algorithm utilizing keywords such as: IgG4 related disease, head and neck, orbit, salivary glands, sialadenitis, Kuttner, angiocentric eosinophilic fibrosis, submandibular, lacrimal, thyroid, dacryoadenitis, nasal, sinus, and Mikulicz's. Reference lists were searched for identification of relevant studies. Case reports, original research and review articles published in English from 1964 to 2014 whose major topic was IgG4-RD affecting the head and neck were included. Data regarding patient demographics, presentation, histopathology, management and treatment outcomes of IgG4-RD were extracted. Level of evidence was also assessed and data were pooled where possible. Three independent reviewers screened eligible studies; extracted relevant data and discrepancies were resolved by consensus, where applicable. Descriptive and comparative statistics were performed.
RESULTS
Fourty-three articles met our inclusion criteria. IgG4-RD most often presents as a mass lesion in the head and neck region. Common diagnostic features include: (1) elevated serum IgG4 level, (2) marked infiltration of exocrine glands by IgG4-positive plasma cells with fibrosis, and (3) marked improvement with corticosteroid therapy and additional immunosuppressive therapy in corticosteroid refractory cases. Early diagnosis and involvement of rheumatology is important in management.
CONCLUSIONS
IgG4-RD is a challenging non-surgical disease that has multiple manifestations in the head and neck. It must be distinguished from various mimics including malignancy, systemic diseases, and infectious. Otolaryngology-Head and Neck surgeons should be aware of this condition and its management.
Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Chronic Disease; Diagnosis, Differential; Humans; Immunoglobulin G; Inflammation; Otorhinolaryngologic Diseases
PubMed: 26092582
DOI: 10.1186/s40463-015-0071-9 -
Advances in Nutrition (Bethesda, Md.) Jun 2021A systematic review was conducted to summarize the absorption, transport, storage, and metabolism of oral neonatal vitamin A supplementation (NVAS). This review focused...
A systematic review was conducted to summarize the absorption, transport, storage, and metabolism of oral neonatal vitamin A supplementation (NVAS). This review focused specifically on the neonatal period (first 28 d of life for humans) to inform guidance by WHO on recommendations related to NVAS. A systematic search of international and regional databases was conducted. Inclusion criteria were human or animal studies that gave oral vitamin A as a single or limited number of doses to apparently healthy neonates. Studies evaluating fortification or food-based approaches, dosing with retinoic acid, or studies of neonatal models of disease were excluded. The search retrieved 8847 unique records. After screening by title and abstract, 88 were screened using the full text, and 35 records met inclusion criteria: 13 human and 22 animal studies. Studies indicate that high-dose NVAS is absorbed well by neonates, typically mirroring fat absorption. Doses were primarily stored in the liver and transiently increased in the lung, kidney, spleen, adrenal glands, brain, skin, and adipose tissue, generally with a dose-response. Serum retinol and retinyl esters also transiently increased following NVAS. Although minimal acute adverse effects are noted, there is a lack of data supporting NVAS for improving organ maturation or sustained delivery to target organs. Research gaps include the physiological effects of the short-term increase of vitamin A concentrations in extrahepatic tissues, or whether there are unknown adverse effects over time.
Topics: Animals; Dietary Supplements; Humans; Infant, Newborn; Liver; Retinyl Esters; Vitamin A; Vitamin A Deficiency
PubMed: 33216111
DOI: 10.1093/advances/nmaa137 -
Egyptian Journal of Forensic Sciences 2022Little is known how COVID-19 is affecting children. Autopsies help gain an understanding of the pathophysiology of new and developing diseases. Numerous post-mortem...
BACKGROUND
Little is known how COVID-19 is affecting children. Autopsies help gain an understanding of the pathophysiology of new and developing diseases. Numerous post-mortem studies had been conducted in adults with COVID-19, but few in children. Thereby, this systematic review aims to investigate the autopsy findings from pediatric COVID-19 patients.
RESULTS
There were a total of 15 patients from eight studies. COVID-19 mainly affects the heart and lungs. Pathology findings from the heart of COVID-19 pediatric patients include diffuse inflammatory infiltrate, myocarditis, cardiomyocyte necrosis, pericarditis, and interstitial edema. Histopathology abnormalities observed in the lungs are diffuse alveolar damage, cytopathic changes, thrombi in arterioles and septal capillaries, lung congestion, focal acute hemorrhage and edema, focal exudative changes, and mild pneumocyte hyperplasia. In addition, pathological findings from other organs, such as the liver, kidney, brain, bone marrow, lymph node, skin, spleen, muscle, colon, parotid gland, and adrenal of COVID-19 pediatric patients are also included in this review.
CONCLUSION
Cardiomyocyte necrosis, interstitial edema, lung congestion, and diffuse alveolar damage are the most significant pathologic findings of the heart and lung in pediatric COVID-19 patients. More studies are needed to elucidate the pathophysiology of SARS-CoV-2 in autopsy findings and to determine the exact cause of death since it could be related to COVID-19 or other comorbidities.
PubMed: 35855892
DOI: 10.1186/s41935-022-00288-0 -
Medicine Dec 2015Pheochromocytoma and paraganglioma (PPG) are rare and late-diagnosed catecholamine secreting tumors, which may be associated with unrecognized and/or severe... (Review)
Review
Pheochromocytoma and paraganglioma (PPG) are rare and late-diagnosed catecholamine secreting tumors, which may be associated with unrecognized and/or severe cardiomyopathies. We performed a computer-assisted systematic search of the electronic Medline databases using the MESH terms "myocarditis," "myocardial infarction," "Takotsubo," "stress cardiomyopathy," "cardiogenic shock", or "dilated cardiomyopathy," and "pheochromocytoma" or "paraganglioma" from 1961 to August 2012. All detailed case reports of cardiomyopathy due to a PPG, without coronary stenosis, and revealed by acute symptoms were included and analyzed. A total of 145 cases reports were collected (49 Takotsubo Cardiomyopathies [TTC] and 96 other Catecholamine Cardiomyopathies [CC]). At initial presentation, prevalence of high blood pressure (87.7%), chest pain (49.0%), headaches (47.6%), palpitations (46.9%), sweating (39.3%), and shock (51.0%) were comparable between CC and TTC. Acute pulmonary edema (58.3% vs 38.8%, P = 0.03) was more frequent in CC. There was no difference in proportion of patients with severe left ventricular systolic dysfunction (LV Ejection Fraction [LVEF] < 30%) at initial presentation between both groups (P = 0.15). LVEF recovery before (64.9% vs 40.8%, P = 0.005) and after surgical resection (97.7% vs 73.3%, P = 0.001) was higher in the TTC group. Death occurred in 11 cases (7.6%). In multivariate analysis, only TTC was associated with a better LV recovery (0.15 [0.03-0.67], P = 0.03). Pheochromocytoma and paraganglioma can lead to different cardiomyopathies with the same brutal and life-threatening initial clinical presentation but with a different recovery rate. Diagnosis of unexplained dilated cardiomyopathy or TTC should lead clinicians to a specific search for PPG.
Topics: Acute Disease; Adrenal Gland Neoplasms; Cardiomyopathies; Chronic Disease; Humans; Pheochromocytoma; Prognosis
PubMed: 26683930
DOI: 10.1097/MD.0000000000002198 -
Minerva Anestesiologica Apr 2002Corticosteroids were proposed to treat patients with severe sepsis as early as 1940. A summary of all available randomized controlled trials performed between 1966 and... (Review)
Review
Corticosteroids were proposed to treat patients with severe sepsis as early as 1940. A summary of all available randomized controlled trials performed between 1966 and 1993 was provided in two systematic review that recommended to abandon the use of high dose coricosteroids to treat patients with severe infection. Nonetheless, a doubt still persist regarding the efficacy of a strategy of replacement therapy in cathecolamines-dependent shock. This strategy relies mainly on the concept that septic shock may be complicated by 1) an occult adrenal insufficiency, 2) a glucocorticoid peripheral resistance syndrome. Some studies demonstrated the effect of replacement therapy with hydrocortisone on the sistemic inflammatory response and on the cardiovascular function during sepsis. The effect of this therapy on survival to septic shock is controversial both in recent and old studies. Finally a recently completed multicenter, placebo controlled, randomized, double-blind study has evaluated the efficacy and tolerance of a replacement therapy with a combination of hydrocortisone (50 mg intravenous bolus four times per day) and fludrocortisone (50 g orally once a day) given for 7 days. This study included 300 catecholamines- and ventilator-dependent septic shock. The authors found a significant reduction in 28-day mortality in patient with occult renal insufficiency. In sum, short course with high doses of corticosteroids should not be given in severe sepsis, except for specific entitles like severe typhoid fever, pneumocystis carinii pneumonia in AIDS or bacterial meningitis in children. The rational for a replacement therapy with hydrocortisone in catecholamines-dependent septic shock grows stronger.
Topics: Adrenal Cortex; Adrenal Cortex Hormones; Hormone Replacement Therapy; Humans; Resuscitation; Sepsis
PubMed: 12024069
DOI: No ID Found -
World Journal of Gastroenterology Oct 2015To investigate the efficacy (survival) and safety of treatments for recurrent hepatocellular carcinoma (HCC) in liver transplantation (LT) patients. (Review)
Review
AIM
To investigate the efficacy (survival) and safety of treatments for recurrent hepatocellular carcinoma (HCC) in liver transplantation (LT) patients.
METHODS
Literature search was performed on available online databases without a time limit until January 2015. Clinical studies describing survival after HCC recurrence in LT patients were retrieved for a full-text evaluation. A total of 61 studies were selected: 13 case reports, 41 retrospective case series, and 7 retrospective comparative studies.
RESULTS
Based on all included studies, the mean HCC recurrence rate was 16% of all LTs for HCC. A total of 1021 LT patients experienced HCC recurrence. The median time from LT to HCC recurrence was 13 mo (range 2-132 mo). The majority of patients (67%) presented with HCC extra-hepatic recurrences, involving lung, bone, adrenal gland, peritoneal lymph nodes, and rarely the brain. Overall survival after HCC recurrence was 12.97 mo. Surgical resection of localized HCC recurrence and Sorafenib for controlling systemic spread of HCC recurrence were associated with the higher survival rates (42 and 18 mo, respectively). However, Sorafenib, especially when combined with mTOR, was frequently associated with severe side effects that required dose reduction or discontinuation
CONCLUSION
Management of recurrent HCC in LT patients is challenging and associated with poor prognosis independently of the type of treatment.
Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local; Niacinamide; Phenylurea Compounds; Protein Kinase Inhibitors; Reoperation; Risk Factors; Sorafenib; Survival Analysis; Time Factors; Treatment Outcome
PubMed: 26494973
DOI: 10.3748/wjg.v21.i39.11185 -
Frontiers in Endocrinology 2023In patients with bilateral pheochromocytoma, partial adrenalectomy offers the chance to preserve adrenal function and avoid the need for lifelong steroid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In patients with bilateral pheochromocytoma, partial adrenalectomy offers the chance to preserve adrenal function and avoid the need for lifelong steroid supplementation. However, the risk of tumour recurrence raises questions about this procedure. The aim of our study was to compare partial and total adrenalectomy in bilateral pheochromocytoma through a systematic review with meta-analysis.
METHODS
A systematic search was carried out using databases (MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL) and registers of clinical trials (ClinicalTrials.gov, European Trials Register, WHO International Trials Registry Platform). This meta-analysis included studies up to July 2022 without language restrictions. A random effects model meta-analysis was performed to assess the risk of tumor recurrence, steroid dependence and morbidity in these patients.
RESULTS
Twenty-five studies were included in the analysis involving 1444 patients. The relative risk (RR) of loss of adrenal hormone function during follow-up and the need for steroid therapy was 0.32 in patients after partial adrenalectomy: RR 0.32, 95% Confidence Interval (CI): 0.26-0.38, P < 0.00001, I2 = 21%. Patients undergoing partial adrenalectomy had a lower odds ratio (OR) for developing acute adrenal crisis: OR 0.3, 95% CI: 0.1-0.91, P=0.03, I2 = 0%. Partial adrenalectomy was associated with a higher risk of recurrence than total adrenalectomy: OR 3.72, 95% CI: 1.54-8.96, P=0.003, I2 = 28%.
CONCLUSION
Partial adrenalectomy for bilateral pheochromocytoma is a treatment that offers a chance of preserving adrenal hormonal function, but is associated with a higher risk of local tumor recurrence. There was no difference for the risk of metastasis and in overall mortality among the group with bilateral pheochromocytomas undergoing total or partial adrenalectomy. This study is in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) Guidelines (10, 11).
SYSTEMATIC REVIEW REGISTRATION
https://osf.io/zx3se.
Topics: Humans; Pheochromocytoma; Neoplasm Recurrence, Local; Adrenalectomy; Adrenal Gland Neoplasms
PubMed: 36998480
DOI: 10.3389/fendo.2023.1127676