Context: In patients with adrenocortical carcinoma (ACC) mitotane activity has been suggested to depend on plasma levels 14mg/liter or greater and metabolite formation. Objective: The study was performed to confirm the correlation of the currently used mitotane (o,p′DDD) threshold of 14 mg/liter with tumor response and to evaluate the additional value of 1,1-(o,p′-dichlorodiphenyl) acetic acid (o,p′DDA) and o,p′DDE (1,1-(o,p′-dichlorodiphenyl)-2,2 dichloroethene) levels for predicting tumor response. Subjects/Methods: Plasma samples collected within 3 months of best response from 91 patients on mitotane therapy for advanced ACC were analyzed retrospectively. O,p′DDD and metabolites were assessed and related to tumor response and survival. Receiver operating characteristic curves were used. Sensitivity and specificity were calculated for different cutoff levels of o,p′DDD and metabolites. Results: Objective tumor response was observed in 19% of patients. Median o,p′DDD level was higher in responders (P = 0.03). More responders were found among patients achieving o,p′DDD levels 14 mg/liter or greater (P = 0.02). Univariate and multivariate analysis showed significantly longer survival for patients with o,p′DDD levels 14 mg/liter or greater (hazard ratio 0.52, P = 0.04, hazard ratio 0.46, P = 0.03). An o,p′DDD cutoff value of 14 mg/liter was associated with a sensitivity of 65% and specificity 69%. An o,p′DDD level 20 mg/liter or greater or 14 mg/liter or greater combined with o,p′DDA level 92 mg/liter or greater was associated with a specificity of 90 and 92%, respectively. Conclusions: Our data confirm the value of o,p′DDD plasma monitoring as well as targeting the 14 mg/liter cutoff level in the therapeutic management of ACC patients. Furthermore, our results suggest additional benefit of higher levels of o,p′DDD and combined measurement of o,p′DDD and o,p′DDA.

Studies on the reliability of the MTS and its predictive power for hospitalisation and mortality in the older population have demonstrated mixed results. The objective is to evaluate the performance of the Manchester Triage System (MTS) in older patients (≥65 years) by assessing the predictive ability of the MTS for emergency department resource utilisation, emergency department length of stay (ED-LOS), hospitalisation, and in-hospital mortality rate. The secondary goal was to evaluate the performance of the MTS in older surgical versus medical patients. A retrospective cohort study was conducted of all emergency department visits by patients ≥65 years between 01 and 09-2011 and 31-08-2012. Performance of the MTS was assessed by comparing the association of the MTS with emergency department resource utilisation, ED-LOS, hospital admission, and in-hospital mortality in older patients and the reference group (18–64 years), and by estimating the area under the receiver operating characteristics curves. Data on 7108 emergency department visits by older patients and 13,767 emergency department visits by patients aged 18–64 years were included. In both patient groups, a higher emergency department resource utilisation was associated with a higher MTS urgency. The AUC for the MTS and hospitalisation was 0.74 (95%CI 0.73–0.75) in older patients and 0.76 (95%CI 0.76–0.77) in patients aged 18–64 years. Comparison of the predictive ability of the MTS for in-hospital mortality in older patients with patients aged 18–64 years revealed an AUC of 0.71 (95%CI 0.68–0.74) versus 0.79 (95%CI 0.72–0.85). The majority of older patients (54.8%) were evaluated by a medical specialty and 45.2% by a surgical specialty. The predictive ability of the MTS for hospitalisation and in-hospital mortality was higher in older surgical patients than in medical patients (AUC 0.74, 95%CI 0.72–0.76 and 0.74, 95%CI 0.68–0.81 versus 0.69, 95%CI 0.67–0.71 and 0.66, 95%CI 0.62–0.69). The performance of the MTS appeared inferior in older patients than younger patients, illustrated by a worse predictive ability of the MTS for in-hospital mortality in older patients. The MTS demonstrated a better performance in older surgical patients than older medical patients regarding hospitalisation and in-hospital mortality.

Objective: Adrenal cortical carcinoma (ACC) is an aggressive tumour with a high mortality. We describe six patients living 12–28 years despite recurrent and/or metastatic ACC.Patients: The first patient presented in 1979 with an ACC of 8 cm. After resection, she developed seven recurrences for which she was treated with resection and/or mitotane (o,p′-DDD) treatment. The patient is still alive 28 years after diagnosis. The second patient presented with an ACC of 9 cm. After resection, the patient developed liver metastases, which were treated witho,p′-DDD. The patient is still alive 25 years after diagnosis. The third patient presented with an ACC of 12 cm. The tumour was resected followed byo,p′-DDD treatment. She had a local recurrence that was completely resected. She is still alive 18 years after diagnosis. The fourth patient presented with an ACC of 14 cm. After resection, adjuvanto,p′-DDD was started. Subsequently, the patient developed two recurrences, which were resected. He is still alive 17 years after the initial diagnosis. The fifth patient presented with an ACC of 10 cm. After diagnosis, she developed lung metastasis, which were treated witho,p′-DDD and chemotherapy. The patient is still alive with slowly progressive disease 12 years after diagnosis. The sixth patient presented with an ACC of 7 cm. After resection, she developed four recurrences, which were resected. The patient is still alive 28 years after diagnosis.Conclusion: Some patients can have an extremely long survival of ACC, despite recurrent disease and metastases. The mainstay of therapy in our patients was repeated surgery ando,p′-DDD.

DNA methylation profiling has been suggested a reliable technique to distinguish between benign and malignant adrenocortical tumors, a process which with current diagnostic methods remains challenging and lacks diagnostic accuracy of borderline tumors. Accurate distinction between benign and malignant adrenal tumors is of the essence, since ACC is a rare but aggressive endocrine disease with an annual incidence of about 2.0 cases per million people per year. The estimated five-year overall survival rate for ACC patients is <50%. However, available treatment regimens are limited, in which a radical surgical resection is the only curable option. Nevertheless, up to 85% of patients with radical resection show recurrence of the local disease often with concurrent metastases. Adrenolytic therapy with mitotane, administered alone or in combination with cytotoxic agents, is currently the primary (palliative) treatment for patients with advanced ACC and is increasingly used in adjuvant setting to prevent recurrence. Prognostic stratification is important in order to individualize adjuvant therapies. On April 1, 2020, there were 7404 publications on adrenocortical carcinoma (adrenocortical carcinoma) OR adrenocortical carcinoma [MeSH Terms]) OR adrenal cortex cancer[MeSH Terms]) OR adrenal cortical carcinoma [MeSH Terms]) OR adrenal cortex neoplasm [MeSH Terms]) OR adrenocortical cancer [MeSH Terms]), yet the underlying pathophysiology and characteristics of ACC is not fully understood. Knowledge on epigenetic alterations in the process of adrenal tumorigenesis is rapidly increasing and will add to a better understanding of the pathogenesis of ACC. DNA methylation profiling has been heralded as a promising method in the prognostication of ACC. This review summarizes recent findings on epigenetics of ACC and its role in diagnosis, prognosis and therapeutic strategies.

Background: Truly patient-centred care needs to be aligned with what patients consider important, and is highly desirable in the first 24 h of an acute admission, as many decisions are made during this period. However, there is limited knowledge on what matters most to patients in this phase of their hospital stay. The objective of this study was to identify what mattered most to patients in acute care and to assess the patient perspective as to whether their treating doctors were aware of this. Methods: This was a large-scale, qualitative, flash mob study, conducted simultaneously in sixty-six hospitals in seven countries, starting November 14th 2018, ending 50 h later. One thousand eight hundred fifty adults in the first 24 h of an acute medical admission were interviewed on what mattered most to them, why this mattered and whether they felt the treating doctor was aware of this. Results: The most reported answers to “what matters most (and why)?” were ‘getting better or being in good health’ (why: to be with family/friends or pick-up life again), ‘getting home’ (why: more comfortable at home or to take care of someone) and ‘having a diagnosis’ (why: to feel less anxious or insecure). Of all patients, 51.9% felt the treating doctor did not know what mattered most to them. Conclusions: The priorities for acutely admitted patients were ostensibly disease- and care-oriented and thus in line with the hospitals’ own priorities. However, answers to why these were important were diverse, more personal, and often related to psychological well-being and relations. A large group of patients felt their treating doctor did not know what mattered most to them. Explicitly asking patients what is important and why, could help healthcare professionals to get to know the person behind the patient, which is essential in delivering patient-centred care. Trial registration: NTR (Netherlands Trial Register) NTR7538.