scholarly journals Adrenocortical Carcinoma in Children: A Clinicopathological Analysis of 41 Patients at the Mayo Clinic from 1950 to 2017

2018 ◽  
Vol 90 (1) ◽  
pp. 8-18 ◽  
Author(s):  
Nidhi Gupta ◽  
Michael Rivera ◽  
Paul Novotny ◽  
Vilmarie Rodriguez ◽  
Irina Bancos ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Mayo Clinic ◽  
Age At Onset ◽  
Survival Rates ◽  
Adrenocortical Adenoma ◽  
Limited Evidence ◽  
Clinicopathological Analysis ◽  
Total Adrenalectomy ◽  
Sites Of Metastases ◽  
Weiss Criteria

Background/Aims: Adrenocortical carcinoma (ACC) is an aggressive childhood cancer. Limited evidence exists on a definite histopathological criterion to differentiate ACC from adrenocortical adenoma. The aim of this study was to investigate the clinicopathological data of children with ACC, identify prognostic factors, and validate a histopathological criterion to differentiate ACC from adrenocortical adenoma. Methods: This retrospective cohort included 41 children, followed at the Mayo Clinic from 1950 to 2017 (onset of symptoms ≤21 years). Outcomes of interest were: alive with no evidence of disease, alive with evidence of disease, and dead of disease. Results: Median age at onset of symptoms was 15.7 years (n = 41; range, 0.2–21 years). Female:male ratio was 3.6: 1. Mixed symptomatology (> 1 hormone abnormality) was the most common presentation (54%, n = 22). Sixty-six percent of patients (n = 27 out of 41) underwent total adrenalectomy. Metastatic disease was more common in children aged > 12 years (p = 0.002 compared to < 4 years). The most common sites of metastases were the liver and lungs. Overall 2-year and 5-year survival rates were 61% (95% CI 45–77) and 46% (95% CI 30–62), respectively. Metastasis at the time of diagnosis was independently associated with poor prognosis (risk ratio 13.7%; 95% CI 3.9–87.7). Weiss criteria (29%) and modified Weiss criteria (33%) were less accurate in younger patients (< 12 years), compared to the Wieneke index (100%). Conclusion: The presence of metastases was an independent prognostic factor. The Wieneke index was the most accurate in predicting clinical outcomes in younger children.

scholarly journals SUN-180 A Case of Deoxycorticosterone-Producing Malignant Adrenocortical Tumor

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Natasha Scaranello Cartolano ◽  
Vânia Balderrama Brondani ◽  
Amanda Meneses Ferreira Lacombe ◽  
Helaine Charchar ◽  
Bruna Pessoa ◽  
...  
Keyword(s):  
Weight Loss ◽  
Arterial Hypertension ◽  
Ct Scan ◽  
Adrenocortical Carcinoma ◽  
Adrenal Mass ◽  
Laboratory Data ◽  
Pulmonary Nodules ◽  
Adrenocortical Tumor ◽  
Abdominal Ct ◽  
Weiss Criteria

Abstract Background: Hypermineralocorticism (hypertension, hypokalemia, and low plasma renin activity) due to deoxycorticosterone (DOC) excess associated with adrenocortical carcinoma is extremely rare. DOC-producing tumors cause primary aldosteronism-like symptoms presenting low plasma aldosterone with very high DOC levels, and due to weak hormonal DOC activity, its diagnostic is done lately. Generally, malignant cases are progressive with a dismal prognosis. Clinical case: A 61-year-old woman was admitted to our hospital presenting lumbar pain and weight loss of 8 kg, in 2018. Previously, arterial hypertension was diagnosed in 2015, showing a satisfactory control with two classes of antihypertensive drugs. Physical exam: The patient presented no features of Cushing syndrome, but a palpable abdominal mass was noticed in the right flank. Blood pressure was 160x100 mmHg, with sustained high levels, despite regular treatment. Laboratory data: a hypokalemia (K 2.4 mEq/L, nr 3.5 -5.0 mEq/L) and hypernatremia (Na 146 mEq/L, nr 135 to 145 mEq/L), with metabolic alkalosis (venous pH 7.46 and serum bicarbonate 32 mmol/L, nr 23-27 mmol/L) was confirmed. Hormonal tests excluded hypercortisolism and pheocromocytoma. Serum aldosterone and renin were suppressed. Mineralocorticoid precursors dosage was extremely high, DOC (654 ng/dL, nr &lt; 25 ng/dL) and progesterone (5.0 ng/mL, nr &lt;0.89 ng/mL), as well 11-deoxycortisol (7.2 ng/mL, nr &lt;0.5 ng/mL). Radiological imaging: abdominal CT showed a heterogeneous hypervascular adrenal mass (13.0x13.0x21.0 cm) exhibiting central necrosis, suggesting malignancy. FDG-PET/CT scan showed a hypermetabolic adrenal mass (SUVmax=13.8). Also, two metabolically active pulmonary nodules (SUVmax=3.7) measuring 0.7 and 0.4 cm were detected. The patient underwent right adrenalectomy, and the tumor was removed (24x13x13 cm). According to Weiss criteria (8/9) and modified Weiss criteria (5/7), the tumor was considered an adrenocortical carcinoma. Immunohistochemistry revealed a low Ki-67 index (10%). After the surgical procedure, all adrenal steroid levels normalized, and mitotane was prescribed as adjuvant therapy. Although the pulmonary nodules were stable at the four-month follow-up, the abdominal CT-scan revealed a heterogeneous nodule (3.7cm) in the left adrenal gland, which was suspicious of metastasis. Conclusion: DOC-producing adrenocortical tumors are heterogeneous regarding tumor size, clinical behavior, hormonal and metabolites secretion, and disease-free and overall survival; however, it is common hypokalemia, hypertension, and other symptoms as abdominal pain, due to tumor growth, and weight loss. The association of arterial hypertension with hypokalemia and elevated 11-deoxycortisol, with normal aldosterone and renin, lead to the need for mineralocorticoid precursors evaluation in patients with adrenocortical tumor.

Surgical Management of Advanced Adrenocortical Carcinoma: A 21-year Population-based Analysis

2013 ◽  
Vol 79 (10) ◽  
pp. 1115-1118 ◽  
Author(s):  
Thuy B. Tran ◽  
Douglas Liou ◽  
Vijay G. Menon ◽  
Nicholas N. Nissen
Keyword(s):  
Surgical Resection ◽  
Adrenocortical Carcinoma ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Stage Iv ◽  
Population Based ◽  
Stage Iii ◽  
Dismal Prognosis ◽  
Advanced Stages ◽  
The Impact

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis. When diagnosed in advanced stages of the disease, the outcomes of surgical resection are not well understood. The objective of this study is to determine the impact of surgery in patients with advanced ACC. Using the Surveillance, Epidemiology and End Results database, we identified patients diagnosed with Stage III and IVACC between 1988 and 2009. A total of 320 patients with Stage III and IV disease were included in our analysis. In patients treated with surgical resection, the Stage III 1- and 5-year survival rates were 77 and 40 per cent, respectively, whereas the Stage IV 1- and 5-year survival rates were 54 and 27.6 per cent, respectively. Patients treated without surgery had poor survival at 1 year for both Stage III (13%) and Stage IV (16%) ( P < 0.01 compared with the surgical groups). Lymph node dissection was performed in 26 per cent of the patients with advanced ACC and was associated with improved survival in univariate analysis of Stage IV patients. Overall, our results indicate that favorable survival outcomes can be achieved even in patients with Stage III and IV disease and surgery should be considered in patients with advanced ACC.

Survival and prognostic factors in 189 dogs with dilated cardiomyopathy

1997 ◽  
Vol 33 (4) ◽  
pp. 364-368 ◽  
Author(s):  
A Tidholm ◽  
H Svensson ◽  
C Sylven
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Age At Onset ◽  
Survival Rates ◽  
Clinical Signs ◽  
Individual Case ◽  
Initial Examination ◽  
Predictive Variables ◽  
One Year ◽  
The Individual

A survival analysis was performed using the case records of 189 dogs, including 38 breeds, with congestive heart failure caused by dilated cardiomyopathy (DCM). Overall prognosis was poor, with survival rates of 17.5% at one year and 7.5% at two years. Prognosis in the individual case of DCM proved to be difficult to predict at the time of initial examination. Only three of 27 tested independent predictors of survival were identified. The most significant predictive variables were age at onset of clinical signs, followed by dyspnea and ascites (as noted on the physical examination).

Clinicopathological analysis of KRAS mutation in an Irish population.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 467-467
Author(s):  
M. Teo ◽  
S. O'Reilly ◽  
E. Moylan ◽  
D. G. Power
Keyword(s):  
Metastatic Disease ◽  
Tumor Resection ◽  
Irish Population ◽  
Wild Type ◽  
Patient Demographics ◽  
Disease Characteristics ◽  
Clinicopathological Analysis ◽  
Kras Status ◽  
Significant Difference ◽  
Sites Of Metastases

467 Background: Clinical trials have shown that tumor KRAS status predicts response to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). We sought to compare distribution of wild-type and mutated KRAS in an Irish population and identify clinicopathologic correlates. Methods: From our prospectively maintained database we retrospectively identified patients with mCRC and documented KRAS status between Jan 2007 to June 2010. Medical notes were examined for patient demographics and disease characteristics. Variables were extracted and compared using unpaired t test and chi2 test. Results: 52 patients were identified, 29 (55.8%) with mutated (mt) and 23 (44.2%) with wild type (wt) KRAS from tumor tissue. Males accounted for 61.5% (n=31). Median age at diagnosis of metastatic disease for the KRASmt group was 66.4 years (range 56.7-82.1) and for the KRAS wt group was 64.2 years (40.1-76.8), p= 0.08. 21 (72.4%) of the KRASmt group and 16 (69.6%) of the KRASwt group had metastatic disease at presentation (p=0.81). For patients who presented initially with localised disease, time to development of metastases was 22.5mo (range 14-37.6) for the KRASmt group and 16.7mo (3.2-123.7) for the KRASwt (p=0.30). 21 (72.4%) of KRASmt and 17 (74.1%) of KRASwt tumors had left-sided primary (p = 0.84) with equal numbers of primary tumor resection in both groups. There was no statistical difference in TN-stage or the presence of liver metastases. Numbers of patients with KRASmt tumors with one, two and three or more different sites of metastases was 22 (75.9%), 5 (17.2%), and 2 (6.9%), and in KRASwt tumors there was no significant difference: 18 (78.3%), 4 (17.4%), and 1 (4.3%), respectively (p = 0.93). Median CEA at diagnosis for both groups were 19.7 μg/l (range 1.2-5958) and 6.1 (1.3-696.9; p = 0.11). Conclusions: We found that the ratio of KRASmt to KRASwt tumours in an Irish population is comparable to that in large international trials. Our analysis revealed no association between KRAS status and clinicopathologic variables. The inclusion of BRAF status, not readily available in our institution, may help define poor prognosis tumors. At present there is no validated molecular biomarker that is superior to standard clinicopathologic variables. No significant financial relationships to disclose.

Properties of partially purified thymidine kinase in adrenal tissue of hyperplasia, adenomatous hyperplasia, adenoma and carcinoma of patients with Cushing's syndrome.

1980 ◽  
Vol 93 (2) ◽  
pp. 208-215 ◽  
Author(s):  
Hajime Nawata ◽  
Ken-ichi Kato ◽  
Hiroshi Ibayashi
Keyword(s):  
Adrenal Gland ◽  
Thymidine Kinase ◽  
Cushing’S Syndrome ◽  
Adrenocortical Carcinoma ◽  
Catalytic Properties ◽  
Deae Cellulose ◽  
Cushing's Syndrome ◽  
Adrenocortical Adenoma ◽  
Adenomatous Hyperplasia ◽  
Adrenocortical Hyperplasia

Abstract. Thymidine kinase (TK) was partially purified from adrenal tissues with adrenocortical hyperplasia, adenomatous hyperplasia, adenoma and carcinoma from patients with Cushing's syndrome and from normal adrenal glands. Adrenocortical carcinoma, adenoma, hyperplasia and nodule and hyperplastic portion of adenomatous hyperplasia contained higher concentration of TK than normal adrenal gland. By DEAE-cellulose column chromatography, adrenocortical carcinoma gave two peaks (Peak I and Peak II) of TK, while in other adrenal tissues the second peak (Peak II) was only slightly detected or hardly detected. TK in all these tissues was identical with respect to pH optimum, metal requirement and inhibition by dTTP. dCTP inhibited TK activities of normal adrenal gland and the hyperplastic portion of adenomatous hyperplasia by 55%, respectively, but hardly affected the activity of the nodule of adenomatous hyperplasia, adenoma, hyperplasia and carcinoma. TK from hyperplastic portion of adenomatous hyperplasia showed the intermediate heat stability between the heat-stable enzyme from normal adrenal gland and the heat-labile enzyme from adrenocortical carcinoma, adenoma, hyperplasia and the nodule of adenomatous hyperplasia. The apparent Km for thymidine from adenocortical carcinoma (Peak I and Peak II) was 5.0 and 11.1; adenoma, 4.8; hyperplasia, 5.5; adenomatous hyperplasia (nodule, 5.0 and hyperplastic portion, 19.8) and normal adrenal gland, 25.0 μm. These observations indicated that TK with different catalytic properties existed in various human adrenal tissues. They also demonstrated that TK isolated from the nodule of adrenocortical adenomatous hyperplasia had similar properties as adrenocortical adenoma, while TK from the hyperplastic portion had the intermediate catalytic properties between normal adrenal gland and adrenocortical hyperplasia.

scholarly journals Frequent POLE-Driven Hypermutation in Ovarian Endometrioid Cancer Revealed by Mutational Signatures in RNA Sequencing

2021 ◽  
Author(s):  
Jaime Davila ◽  
Pritha Chanana ◽  
Vivekananda Sarangi ◽  
Zach Fogarty ◽  
John Weroha ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Mayo Clinic ◽  
Somatic Mutations ◽  
Age At Onset ◽  
The Cancer Genome Atlas ◽  
Driver Mutations ◽  
Rna Seq ◽  
Mutational Signatures ◽  
Mutational Signature ◽  
Hotspot Mutations

Abstract Background: DNA polymerase epsilon (POLE) is encoded by the POLE gene, and POLE-driven tumors are characterized by high mutational rates. POLE-driven tumors are relatively common in endometrial and colorectal cancer, and their presence is increasingly recognized in ovarian cancer (OC) of endometrioid type. POLE-driven cases possess an abundance of TCT>TAT and TCG>TTG somatic mutations characterized by mutational signature 10 from the Catalog of Somatic Mutations in Cancer (COSMIC). By quantifying the contribution of COSMIC mutational signature 10 in RNA sequencing (RNA-seq) we set out to identify POLE-driven tumors in a set of unselected Mayo Clinic OC. Methods: Mutational profiles were calculated using expressed single-nucleotide variants (eSNV) in the Mayo Clinic OC tumors (n=195), The Cancer Genome Atlas (TCGA) OC tumors (n=419), and the Genotype-Tissue Expression (GTEx) normal ovarian tissues (n=84). Non-negative Matrix Factorization (NMF) of the mutational profiles inferred the contribution per sample of four distinct mutational signatures, one of which corresponds to COSMIC mutational signature 10. Results: In the Mayo Clinic OC cohort we identified six tumors with a predicted contribution from COSMIC mutational signature 10 of over five mutations per megabase. These six cases harbored known POLE hotspot mutations (P286R, S297F, V411L, and A456P) and were of endometrioid histotype (P=5e-04). These six tumors were hypermutated with a higher tumor mutation load (mean, 54.02 mutations per megabase) compared to non-POLE endometrioid OC cases (mean, 7.69 mutations per megabase; P=5e-04), and had an early onset (average age of patients at onset, 48.33 years) when compared to non-POLE endometrioid OC cohort (average age at onset, 60.13 years; P=.008). Samples from TCGA and GTEx had a low COSMIC signature 10 contribution (median 0.16 mutations per megabase; maximum 1.78 mutations per megabase) and carried no POLE hotspot mutations.Conclusions: From the largest cohort of RNA-seq from endometrioid OC to date (n=53), we identified six hypermutated samples likely driven by POLE (frequency, 11%). Our result suggests the clinical need to screen for POLE driver mutations in endometrioid OC, which can guide enrollment in immunotherapy clinical trials.

Outcomes in juvenile onset lupus: single center cohort from a developing country

Lupus ◽  
2018 ◽  
Vol 27 (11) ◽  
pp. 1867-1875 ◽  
Author(s):  
A Aggarwal ◽  
S Phatak ◽  
P Srivastava ◽  
A Lawrence ◽  
V Agarwal ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Age At Onset ◽  
Survival Rates ◽  
Laboratory Data ◽  
Developed Countries ◽  
Indian Children ◽  
Actuarial Survival ◽  
Cns Disease ◽  
Kaplan Meier

Introduction About 10–20% of systemic lupus erythematosus (SLE) patients have onset in childhood and have more severe organ involvement. Survival of juvenile SLE patients is improving worldwide. Long-term data of childhood onset SLE from developing countries is scarce. Methods Clinical and laboratory data at initial presentation and follow-up visits were retrieved from clinic files, hospital information system and personal interviews. Treatment received, complications, flares, outcomes and death were recorded. Survival was calculated using Kaplan–Meier survival curves and regression analysis was done for predictors of mortality. Results Children with SLE ( n = 273, 250 girls) had a median age at onset of 14 years and duration of illness prior to diagnosis at our hospital of 1 year. Fever and arthritis were the most common presenting manifestations. Renal disease was seen in 60.5% and central nervous system (CNS) disease in 29%. The median follow-up period in 248 patients was 3.5 years. Fourteen children died, and 10 of these had active disease at the time of death. The mean actuarial survival was 24.5 years and survival rates at 1, 5 and 10 years were 97.9%, 95% and 89% respectively. Fever, CNS disease, anti-dsDNA levels and serious infections predicted death on univariate and multivariate analysis. Infections were seen in 72 children (26.3%), and 38 of these infections were serious. One-third of the patients had damage on the last follow-up. Flares were seen in 120 children, the majority being major flares. Conclusion Outcomes of pediatric SLE in North Indian children are similar to those seen in developed countries. Infections pose a major challenge in these patients.

scholarly journals Revisiting the cognitive buffer hypothesis for the evolution of large brains

2008 ◽  
Vol 5 (1) ◽  
pp. 130-133 ◽  
Author(s):  
Daniel Sol
Keyword(s):  
Survival Rates ◽  
Buffer Effect ◽  
Limited Evidence ◽  
Behavioural Responses ◽  
Delayed Reproduction ◽  
Behavioural Patterns ◽  
Large Brain ◽  
Reproductive Life

Why have some animals evolved large brains despite substantial energetic and developmental costs? A classic answer is that a large brain facilitates the construction of behavioural responses to unusual, novel or complex socioecological challenges. This buffer effect should increase survival rates and favour a longer reproductive life, thereby compensating for the costs of delayed reproduction. Although still limited, evidence in birds and mammals is accumulating that a large brain facilitates the construction of novel and altered behavioural patterns and that this ability helps dealing with new ecological challenges more successfully, supporting the cognitive-buffer interpretation of the evolution of large brains.

scholarly journals Clinicopathological Features of Pediatric Functional Adrenocortical Carcinoma Diagnosed by Weiss Criteria; An Analysis of Four Cases

2001 ◽  
Vol 10 (2) ◽  
pp. 141-146 ◽  
Author(s):  
Yoko Misu ◽  
Shi-Xu Jiang ◽  
Yukifumi Yokota ◽  
Masahiko Shibata ◽  
Osamu Shinohara ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Clinicopathological Features ◽  
Weiss Criteria
Sign in / Sign up

Export Citation Format

Share Document