Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible ...evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en bloc resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.
Background:
Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently.
Objective:
The aim of this study was to identify markers with prognostic value for ...patients in this clinical setting.
Design, Setting, and Participants:
From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I–III were identified. As an independent validation cohort, 250 patients from three European countries were included.
Outcome Measurements and Statistical Analysis:
Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS).
Results:
Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio HR for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10–19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone.
Conclusion:
This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC.
Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity ...of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC.
We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU.
Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value PPV 19·7%, 95% CI 16·2–23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% 95% CI 77·9–82·0 vs 64·0% 61·4–66.4) while maintaining sensitivity (99·0% 94·4–100·0 vs 100·0% 96·3–100·0; PPV 19·7%, 16·3–23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6–41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2–84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4–100·0).
An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours.
European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
OBJECTIVETo evaluate the effect of chenodeoxycholic acid treatment on disease progression in cerebrotendinous xanthomatosis (CTX).
METHODSIn this retrospective cohort study, we report the clinical ...long-term follow-up characteristics of 56 Dutch patients with CTX. Age at diagnosis was correlated with clinical characteristics and with the course of modified Rankin Scale (mRS) and Expanded Disability Status Scale (EDSS) scores at follow-up.
RESULTSMedian follow-up time was 8 years (6 months–31.5 years). Patients diagnosed and treated before the age of 24 years had a significantly better outcome at follow-up. When considering only patients with a good treatment adherence (n = 43), neurologic symptoms, if present, disappeared in all patients who were diagnosed before the age of 24 and treated since. Furthermore, treatment prevented the development of new neurologic symptoms during follow-up. In contrast, 61% of the patients diagnosed and treated after the age of 24 showed deterioration of the neurologic symptoms, with parkinsonism as a treatment-resistant feature. There was an improvement or stabilization in favor of patients diagnosed and treated before the age of 24 compared to those treated after the age of 24100% vs 58% for mRS scores and 100% vs 50% for EDSS scores, respectively.
CONCLUSIONSTreatment start at an early age can reverse and even prevent the development of neurologic symptoms in CTX. This study emphasizes the importance of early diagnosis in CTX and provides a rationale to include CTX in newborn screening programs.
To assess the association of patient and organisational factors with emergency department length of stay (ED-LOS) in elderly ED patients (226565 years old) and in younger patients (<65 years old).
A ...retrospective cohort study of internal medicine patients visiting the emergency department between September 1st 2010 and August 31st 2011 was performed. All emergency department visits by internal medicine patients 226565 years old and a random sample of internal medicine patients <65 years old were included. Organisational factors were defined as non-medical factors. ED-LOS is defined as the time between ED arrival and ED discharge or admission. Prolonged ED-LOS is defined as ≥75th percentile of ED-LOS in the study population, which was 208 minutes.
Data on 1782 emergency department visits by elderly patients and 597 emergency department visits by younger patients were analysed. Prolonged ED-LOS in elderly patients was associated with three organisational factors: >1 consultation during the emergency department visit (odds ratio (OR) 3.2, 95% confidence interval (CI) 2.3-4.3), a higher number of diagnostic tests (OR 1.2, 95% CI 1.16-1.33) and evaluation by a medical student or non-trainee resident compared with a medical specialist (OR 4.2, 95% CI 2.0-8.8 and OR 2.3, 95% CI 1.4-3.9). In younger patients, prolonged ED-LOS was associated with >1 consultation (OR 2.6, 95% CI 1.4-4.6). Factors associated with shorter ED-LOS were arrival during nights or weekends as well as a high urgency level in elderly patients and self-referral in younger patients.
Organisational factors, such as a higher number of consultations and tests in the emergency department and a lower seniority of the physician, were the main aspects associated with prolonged ED-LOS in elderly patients. Optimisation of the organisation and coordination of emergency care is important to accommodate the needs of the continuously growing number of elderly patients in a better way.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Non-specific complaints (NSC) are common at the emergency department, but only a few studies have shown evidence that these complaints are associated with a poor prognosis in elderly emergency ...patients.
To describe patient characteristics and outcomes in a cohort of elderly emergency patients presenting with NSC. Outcomes were: patient characteristics, hospitalization, 90-day ED-return visits, and 30-day mortality.
A retrospective cohort study was conducted amongst elderly patients present to the Internal Medicine Emergency Department (ED) between 01-09-2010 and 31-08-2011. NSC were defined as indefinable complaints that lack a pre-differential diagnosis needed to initiate of a standardized patient evaluation. Cox regression was performed to calculate Hazard Ratios (HR) and corrected for confounders such as comorbidity.
In total, 1784 patients were enrolled; 244 (13.7%) presented with NSC. Compared to those with SC, comorbidity was higher in the NSC-group (Charlson comorbidity index 3.0 vs. 2.4, p<0.001). The triage level did not differ, but ED-length of stay was longer in the NSC-group (188 vs. 178 minutes, p = 0.004). Hospitalization was more frequent (84.0 vs. 71.1%, p<0.001) and the length of hospital stay (9 vs. 6 days, p<0.001 was longer in the NSC- than in the SC-group. The number of ED-return visits were comparable between both groups (HR 0.8, 95%CI 0.6-1.1). Mortality within 30-days was higher in the NSC- (20.1%) than in the SC-group (11.0%, HR 1.7 95%CI 1.2-2.4).
Elderly patients present with NSC at the ED regularly. These patients are more often hospitalized and have a substantially higher 30-day mortality than patients with SC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Although inadequate sleep has a proven negative association with health care outcomes, to date, no large-scale studies have examined sleep in general hospital wards. OBJECTIVES: To assess ...the subjective quantity and quality of sleep and to identify the hospital-related factors associated with sleep disturbances in hospitalized patients. DESIGN: For this nationwide, single-day, multicenter, cross-sectional, observational study, which took place on February 22, 2017, all hospitals in the Netherlands were encouraged by word of mouth and conventional and social media to participate in this study. A total of 39 hospitals participated. Included patients were at least 18 years of age, were able to give informed consent, and had spent at least 1 night in a regular-care hospital ward. EXPOSURES: Hospitalization in a regular-care ward. MAIN OUTCOMES AND MEASURES: Quantity and quality of last night's sleep in the hospital compared with habitual sleep at home the month before hospitalization. The Consensus Sleep Diary and the Dutch-Flemish Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance item bank were used. Complementary questions assessed sleep-disturbing factors. RESULTS: A total of 2005 patients were included (median age, 68 years; interquartile range, 57-77 years; 994 of 1935 51.4% were male 70 patients did not identify their sex). Compared with habitual sleep at home, the total sleep time in the hospital was 83 minutes (95% CI, 75-92 minutes; P < .001) shorter. The mean number of nocturnal awakenings was 2.0 (95% CI, 1.9-2.1) times at home vs 3.3 (95% CI, 3.2-3.5) times during hospitalization (P < .001). Patients woke up 44 minutes (95% CI, 44-45 minutes; P < .001) earlier than their habitual wake-up time at home. A total of 1344 patients (70.4%) reported having been awakened by external causes, which in 718 (35.8%) concerned hospital staff. All aspects of sleep quality measured using PROMIS questions were rated worse during hospitalization than at home. The most reported sleep-disturbing factors were noise of other patients, medical devices, pain, and toilet visits. CONCLUSIONS AND RELEVANCE: This study demonstrated that the duration and quality of sleep in hospitalized patients were significantly affected and revealed many potentially modifiable hospital-related factors negatively associated with sleep. Raising awareness about the importance of adequate sleep in the vulnerable hospital population and introducing interventions to target sleep-disturbing factors may improve healing.
Abstract
Context
Pretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL).
...Objective
To determine which type of α-adrenergic receptor blocker provides the best efficacy.
Design
Randomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898)
Setting
Multicenter study including 9 centers in The Netherlands.
Patients
134 patients with nonmetastatic PPGL.
Intervention
Phenoxybenzamine or doxazosin starting 2 to 3 weeks before surgery using a blood pressure targeted titration schedule. Intraoperative hemodynamic management was standardized.
Main Outcome Measures
Primary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (ie, SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score.
Results
Median cumulative time outside blood pressure targets was 11.1% (interquartile range IQR: 4.3–20.6 in the phenoxybenzamine group compared to 12.2% (5.3–20.2) in the doxazosin group (P = .75, r = 0.03). The hemodynamic instability score was 38.0 (28.8–58.0) and 50.0 (35.3–63.8) in the phenoxybenzamine and doxazosin group, respectively (P = .02, r = 0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P = .68). There was no mortality after 30 days.
Conclusions
The duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome.
Abstract Background The reported annual incidence of adrenocortical carcinoma (ACC) is 0.5–2.0 cases per million individuals. Updated population-based studies on incidence are lacking. The aim of ...this nationwide survey was to describe the incidence and survival rates of ACC in the Netherlands. Secondary objectives were to evaluate changes in both survival rates and the number of patients undergoing surgery. Methods All ACC patients registered in the Netherlands Cancer Registry (NCR) between 1993 and 2010 were included. Data on demographics, stage of disease, primary treatment modality and survival were evaluated. Results Included were 359 patients, 196 of whom were female (55%). Median age at diagnosis was 56 years (range 1–91). The 5-year age-standardised incidence rate decreased from 1.3 to 1.0 per one million person-years. Median survival for patients with stage I–II, stage III and stage IV disease was 159 months (95% confidence interval (CI) 93–225 months), 26 months (95% CI: 4–48 months) and 5 months (95% CI: 2–7 months), respectively ( P < 0.001). Improvement in survival was not observed, as reflected by the lack of association between survival and time of diagnosis. The percentage of patients receiving treatment within 6 months after diagnosis increased significantly from 76% in 1993–1998 to 88% in 2005–2010 ( P = 0.047), mainly due to an increase in surgery for stage III–IV patients. Conclusion These nationwide data provide an up-to-date survey of the epidemiology of ACC in the Netherlands. A trend towards a decreasing overall incidence rate was observed. Survival rates did not change during this period despite an increased number of surgical procedures.
Providing high quality care is important and has gained more attention since the introduction of value-based healthcare. Value should be measured by outcomes achieved, relevant for patients. ...Patient-centeredness is one domain for quality improvement determined by the Institute of Medicine, aiming to deliver care responsive to the patient. The development and implementation of patient reported outcome- and experience measures can be used for this goal. Recently, we developed the Patient Reported Measure (PRM)-acute care, based on five relevant domains to evaluate and improve the quality of care in the Emergency Department (ED).
To validate the PRM-acute care, in order to evaluate and improve patient-centered care in the ED.
We performed a prospective questionnaire-based study. Patients ≥18 years presenting for internal medicine in the ED were eligible. The validity of the PRM-acute care was evaluated according to the COSMIN-criteria. We performed hypotheses testing to evaluate construct validity. The perceived quality of care was evaluated by statistical analysis.
Face- and content validity was evaluated based on previously performed research and deemed good. Construct validity was supported by demonstrated differences between subgroups; patients with severe symptoms had a higher perceived quality of care. The correlation between overall satisfaction and the total mean score of the PRM-acute care (r = 0,447, p = 0.01) was significant. Overall, patients reported a mean perceived quality of care of 4.67/6.0.
The PRM-acute care is a valid instrument to measure the perceived quality of care in an acute setting for internal medicine patients. Additionally, patients reported a good perceived quality of care in the ED with scores ranging from moderate to well for each of the relevant domains. Therefore, we believe that the PRM-acute care can be implemented in daily practice to evaluate the perceived quality of care and to improve the quality of acute care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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