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Cancers Oct 2021Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a... (Review)
Review
Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81%-local recurrence, 19% ( = 65)-distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival ( < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.
PubMed: 34771430
DOI: 10.3390/cancers13215266 -
Endocrinology, Diabetes & Metabolism Jul 2022Adrenocortical carcinoma (ACC) is a rare cancer with an annual incidence of 0.7-2 cases per million population and 5-year survival of 31.2%. Adrenal insufficiency (AI)... (Review)
Review
INTRODUCTION
Adrenocortical carcinoma (ACC) is a rare cancer with an annual incidence of 0.7-2 cases per million population and 5-year survival of 31.2%. Adrenal insufficiency (AI) is a common and life shortening complication of ACC, and little is understood about how it impacts on patients' experience.
OBJECTIVE
To understand patients' lived experience of the condition, its treatment, care process, impact of AI on ACC wellbeing, self-care needs and support.
METHODS
Systematic review of MEDLINE, EMBASES, CINAHL, PsycINFO and Open Grey for studies published until February 2021. All research designs were included. The findings underwent a thematic analysis and narrative synthesis. Studies quality was assessed using mixed method assessment tools.
RESULTS
A total of 2837 citations were identified; 15 titles with cohort, cross-sectional, case series and case report study designs met the inclusion criteria involving 479 participants with adrenal insufficiency secondary to adrenocortical carcinoma (AI/ACC). Quantitative research identified impacts of disease and treatment on survivorship, the burden of living with AI/ACC, toxicity of therapies, supporting self-care and AI management. These impact factors included adjuvant therapies involved and their toxicities, caregivers/family supports, healthcare and structure support in place, specialist skill and knowledge provided by healthcare professional on ACC management. No qualitative patient experiences evidence was identified.
CONCLUSION
ACC appears to have high impact on patients' wellbeing including the challenges with self-care and managing AI. Evidence is needed to understand patient experience from a qualitative perspective.
Topics: Adrenal Cortex Neoplasms; Adrenal Insufficiency; Adrenocortical Carcinoma; Caregivers; Cross-Sectional Studies; Humans
PubMed: 35670031
DOI: 10.1002/edm2.341 -
JSLS : Journal of the Society of... 2015Adrenocortical cancer (ACC) is a rare disease that is difficult to treat. Laparoscopic adrenalectomy (LA) is performed, even for large adrenocortical carcinomas.... (Review)
Review
BACKGROUND
Adrenocortical cancer (ACC) is a rare disease that is difficult to treat. Laparoscopic adrenalectomy (LA) is performed, even for large adrenocortical carcinomas. However, the oncological effectiveness of LA remains unclear. This review presents the current knowledge of the feasibility and oncological effectiveness of laparoscopic surgery for ACC, with an analysis of data for outcomes and other parameters.
DATABASE
A systematic review of the literature was performed by searching the PubMed and Medline databases for all relevant articles in English, published between January 1992 and August 2014 on LA for adrenocortical carcinoma.
DISCUSSION
The search resulted in retrieval of 29 studies, of which 10 addressed the outcome of LA versus open adrenalectomy (OA) and included 844 patients eligible for this review. Among these, 206 patients had undergone LA approaches, and 638 patients had undergone OA. Among the 10 studies that compared the outcomes obtained with LA and OA for ACC, 5 noted no statistically significant difference between the 2 groups in the oncological outcomes of recurrence and disease-free survival, whereas the remaining 5 reported inferior outcomes in the LA group. Using a paired t test for statistical analysis, except for tumor size, we found no significant difference in local recurrence, peritoneal carcinomatosis, positive resection margin, and time to recurrence between the LA and OA groups. The overall mean tumor size in patients undergoing LA and OA was 7.1 and 11.2 cm, respectively (P = .0003), and the mean overall recurrence was 61.5 and 57.9%, respectively. The outcome of LA is believed to depend to a large extent on the size and stage of the lesion (I and II being favorable) and the surgical expertise in the center where the patient undergoes the operation. However, the present review shows no difference in the outcome between the 2 approaches across all stages. A poor outcome is likely to result from inadequate surgery, irrespective of whether the approach is open or laparoscopic.
Topics: Adrenal Cortex Neoplasms; Adrenalectomy; Adrenocortical Carcinoma; Humans; Laparoscopy
PubMed: 26175553
DOI: 10.4293/JSLS.2015.00036 -
Biomedicines Oct 2021Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis and a high rate of recurrence and mortality. Therapeutic options are limited. In... (Review)
Review
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis and a high rate of recurrence and mortality. Therapeutic options are limited. In some cases, the distinction of ACCs from benign adrenal neoplasms with the existing widely available pathological and histopathological tools is difficult. Thus, new biomarkers have been tested. We conducted a review of the recent literature on the advances of the diagnostic, prognostic and therapeutic role of miRNAs on ACC patients. More than 10 miRNAs validated by multiple studies were found to present a diagnostic and prognostic role for ACC patients, from which miR-483-5p and miR-195 were the most frequently met biomarkers. In particular, upregulation of miR-483-5p and downregulation of miR-195 were the most commonly validated molecular alterations. Unfortunately, data on the therapeutic role of miRNA are still scarce and limited mainly at the experimental level. Thus, the role of miRNA regulation in ACC remains an area of active research.
PubMed: 34829730
DOI: 10.3390/biomedicines9111501 -
AJR. American Journal of Roentgenology Feb 2020The objective of this systematic review was to determine the number and quality of reports of adrenocortical carcinoma (ACC) containing macroscopic fat; this...
The objective of this systematic review was to determine the number and quality of reports of adrenocortical carcinoma (ACC) containing macroscopic fat; this information may inform guidelines for diagnosis and management of ACC. A comprehensive search of databases of published studies was performed. Two reviewers independently selected original research, case series, or case reports of ACC with macroscopic fat on imaging and extracted data. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Three case reports and one retrospective study comprising a total of seven cases of ACC (lesion size: range, 6.5-22 cm) with macroscopic fat were included. ACC was symptomatic in all patients; neither locally invasive features nor metastases were reported. Four cases had less than 5% macroscopic fat on imaging, and the percentage fat on imaging was not reported for the remaining three cases. With regard to the risk of bias, one case had high risk for the index test domain because of potentially unreliable determination of macroscopic fat (i.e., no pathologic confirmation). All seven cases (from four studies) had unclear risk for the reference standard domain because there was insufficient information about the reference standard to determine whether ACC was correctly diagnosed. All studies were at low risk of bias in the flow and timing domain. There are few reports of macroscopic fat in ACC detected on imaging studies; among the reports of macroscopic fat in ACC, tumors were large (> 6 cm) and had a small proportion of gross fat (< 5%). The reliability of reported cases is questionable primarily because of insufficient details about pathologic diagnosis. Based on this information, a change in guideline recommendations may not be warranted. However, consideration of follow-up or biopsy of patients with large symptomatic tumors (> 6 cm) containing a small proportion of fat (< 5%) may be appropriate.
Topics: Adipose Tissue; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Humans
PubMed: 31691613
DOI: 10.2214/AJR.19.21851 -
Annals of Surgical Oncology Feb 2023Laparoscopic surgery is considered a standard treatment for benign adrenal tumors; however, no consensus has been reached on the optimal resection technique for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Laparoscopic surgery is considered a standard treatment for benign adrenal tumors; however, no consensus has been reached on the optimal resection technique for adrenocortical carcinomas. This study aims to evaluate the safety and efficacy of laparoscopic surgery and open surgery in the management of adrenocortical carcinoma.
METHODS
The Cochrane, Embase, PubMed, Scopus, and Web of Science databases were searched for articles from inception to May 2022, by two independent reviewers using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. The review was registered prospectively on the PROSPERO database (CRD42022316050).
RESULTS
From 183 studies screened, 11 studies met the eligibility criteria, with a total of 1617 patients with adrenocortical carcinoma undergoing either laparoscopic surgery (n = 472) or open surgery (n = 1145). Open surgery demonstrated a lower rate of positive resection margin compared with laparoscopic surgery (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.10-2.10; I = 0%). Additionally, open surgery had more favorable overall survival (OR 0.56, 95% CI 0.44-0.72; I = 0%) and recurrence-free rates (OR 0.60, 95% CI 0.42-0.85; I = 38%) than laparoscopic surgery at 3 years. Hospital stay was shorter for laparoscopic surgery than open surgery (mean difference - 2.49 days, 95% CI - 2.95 to - 2.04; I = 45%).
CONCLUSIONS
Open surgery should still be considered the standard operative approach; however, laparoscopic surgery could be regarded as an effective and safe operation for selected adrenocortical carcinoma cases with appropriate laparoscopic expertise. Further randomized controlled studies with tumor stage- and resection margin-dependent survival analysis are necessary to ascertain the safety and efficacy of the treatment.
Topics: Humans; Adrenocortical Carcinoma; Margins of Excision; Laparoscopy; Adrenal Cortex Neoplasms; Treatment Outcome
PubMed: 36344710
DOI: 10.1245/s10434-022-12711-w -
Cancers Oct 2021Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this... (Review)
Review
Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this systematic review is to collect the available evidence on the side effects of mitotane on the endocrine and metabolic systems in both children and adults affected by adrenal carcinoma. Sixteen articles on 493 patients were included. Among the adrenal insufficiency, which is an expected side effect of mitotane, 24.5% of patients increased glucocorticoid replacement therapy. Mineralocorticoid insufficiency usually occurred late in treatment in 36.8% of patients. Thyroid dysfunction is characterized by a decrease in FT4, which occurs within 3-6 months of treatment in 45.4% of patients, while TSH seems to not be a reliable marker. Dyslipidemia is characterized by an increase in both LDL-c and HDL-c (54.2%). Few studies have found evidence of hypertriglyceridemia. In males, gynecomastia and hypogonadism can occur after 3-6 months of treatment (38.4% and 35.6%, respectively), while in pre-menopausal women, mitotane can cause ovarian cysts and, less frequently, menstrual disorders. Most of these side effects appear to be reversible after mitotane discontinuation. We finally suggest an algorithm that could guide metabolic and endocrine safety assessments in patients treated with mitotane for ACC.
PubMed: 34638485
DOI: 10.3390/cancers13195001 -
Frontiers in Surgery 2022Adrenocortical carcinoma (ACC) is a rare neoplasm with a high recurrence rate. This study aimed to assess the role of surgery in the clinical management of recurrent ACC.
BACKGROUND
Adrenocortical carcinoma (ACC) is a rare neoplasm with a high recurrence rate. This study aimed to assess the role of surgery in the clinical management of recurrent ACC.
METHODS
The PubMed, Embase, Web of Science, and Cochrane Library databases were searched, and the hazard ratios were pooled.
RESULTS
Patients who underwent resection for recurrence had significantly better OS or OS after recurrence than those who received only nonsurgical treatments (HR 0.34, < 0.001). Prognostic factors were associated with decreased OS after recurrence, including multiple recurrence (HR 3.23, = 0.001), shorter disease-free interval (HR 2.94, < 0.001), stage III-IV of the original tumor (HR 6.17, = 0.001), sex of male (HR 1.35, = 0.04), and initial non-R0 resection (HR 2.13, = 0.001). Prolonged OS after recurrence was observed in those who experienced incomplete resection (HR 0.43, 95% CI 0.31-0.52, I = 53%) compared with patients who only received nonsurgical treatments. In the reoperated group, patients who underwent complete resection of recurrence had a prolonged OS after recurrence compared with those who underwent incomplete resection (HR 0.23, = 0.004).
CONCLUSIONS
We confirmed the role of reoperation in the clinical management of recurrent ACC. Select patients might benefit from debulking surgery. The preoperative evaluation of the complete resection of the recurrence is the key means to decide whether patients should undergo surgery. Other prognostic factors associated with prolonged OS include single recurrence site, relatively longer disease-free interval, stage I-II of the original tumor, and female sex.
PubMed: 35252325
DOI: 10.3389/fsurg.2022.781406 -
Clinical Genitourinary Cancer Feb 2023Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare... (Review)
Review
A Systematic Review of Published Clinical Trials in the Systemic Treatment of Adrenocortical Carcinoma: An Initiative Led on Behalf of the Global Society of Rare Genitourinary Tumors.
Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare disease. We aimed to perform a systematic review of the literature on systemic therapy options in different stages of ACC. A systematic review was performed using Pubmed and Embase databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 24 trials of systemic therapy in the treatment of ACC were identified and included in this review. Only one clinical trial in the adjuvant setting was identified, the negative phase III trial ADIUVO, which tested mitotane in low to intermediate-risk ACC patients. In the treatment of advanced ACC, cisplatin-based chemotherapy was evaluated in small and non-randomized phase II trials, and response rates ranged from 21% to 53.5%. The phase III trial FIRM-ACT compared etoposide, doxorubicin, cisplatin, and mitotane versus treatment with streptozotocin and mitotane and showed no difference in OS, but higher RR and PFS were reported with the multi-drug regimen. Six clinical trials of immunotherapy and seven studies of targeted therapy in advanced ACC were included, with modest activity and no phase 3 trials were identified. Treatment recommendations of ACC are based on retrospective and small studies with limited systemic therapy options. International and multi-center collaboration is essential to expand clinical research and improve outcomes.
Topics: Humans; Adrenocortical Carcinoma; Mitotane; Adrenal Cortex Neoplasms; Cisplatin; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36376169
DOI: 10.1016/j.clgc.2022.10.011 -
Cancers Jan 2022(1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are... (Review)
Review
(1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement. The primary outcome was the impact of lymphadenectomy on overall survival (OS). Two separate meta-analyses were performed for studies including patients with localized ACC (stage I-III) and those including all tumor stages (I-IV). Secondary endpoints included postoperative mortality and length of hospital stay (LOS). (3) Results: 11 publications were identified for inclusion. All studies were retrospective studies, published between 2001-2020, and 5 were included in the meta-analysis. Three studies ( = 807 patients) reported the impact of LND on disease-specific survival in patients with stage I-III ACC and revealed a survival benefit of LND (hazard ratio (HR) = 0.42, 95% confidence interval (95% CI): 0.26-0.68). Based on results of studies including patients with ACC stage I-IV (2 studies, = 3934 patients), LND was not associated with a survival benefit (HR = 1.00, 95% CI: 0.70-1.42). None of the included studies showed an association between LND and postoperative mortality or LOS. (4) Conclusion: Locoregional lymphadenectomy seems to offer an oncologic benefit in patients undergoing curative-intended surgery for localized ACC (stage I-III).
PubMed: 35053453
DOI: 10.3390/cancers14020291