Characteristics of a Family with the MEN-2A Syndrome

Results of screening and follow-up in a family with the MEN-2A syndrome are described. Fourteen (83%) subjects at risk were affected with medullary thyroid carcinoma (MTC). Asymptomatic pheochromocytoma and parathyroid hyperplasia were found in two instances each. Intrathyroidal MTC without metastases was found in the four youngest subjects and was associated with normal basal but abnormal pentagastrin-stimulated calcitonin (CT) levels. In the ten subjects with abnormal basal CT levels, metastatic spread to at least regional lymph nodes was found. In eight of these ten subjects, total thyroidectomy with excision of affected lymph nodes and additional radioiodine did not return CT levels to normal postoperatively. In the other two subjects, the CT levels returned to normal after thyroidectomy and an ablative dose of radioiodine, and remained normal during follow-up. This study confirms the view that family screening at a young age promotes the detection of MTC at a curable stage. Radioiodine as an adjunct to surgery may be of value in the prevention of tumor recurrence in patients with normal postoperative CT levels but residual thyroid tissue

Diabetes alone should not be a reason for withholding adjuvant chemotherapy for stage III colon cancer

Background: With increasing prevalence of diabetes mellitus and colon cancer, the number of patients suffering from both diseases is growing, and physicians are being faced with complicated treatment decisions. Objective: To investigate the association between diabetes and treatment/course of stage III colon cancer and the association between colon cancer and course of diabetes. Materials and Methods: Additional information was collected from the medical records of all patients with both stage III colon cancer and diabetes (n=201) and a random sample of stage III colon cancer patients without diabetes (n=206) in the area of the population-based Eindhoven Cancer Registry (1998–2007). Results: Colon cancer patients without diabetes were more likely to receive adjuvant chemotherapy compared with diabetic colon cancer patients (OR 1.8; 95% CI 1.2–2.7). After adjustment for age, this difference was borderline significant (OR 1.6; 95% CI 1.0–2.6). Diabetic patients did not have: significantly more side-effects from surgery or adjuvant chemotherapy; more recurrence from colon cancer; significantly shorter time interval until recurrence; or a poorer disease-free survival or overall survival. Age and withholding of adjuvant chemotherapy were most predictive of all-cause mortality. After colon cancer diagnosis, the dose of antiglycaemic medications was increased in 22% of diabetic patients, resulting in significantly lower glycaemic indexes than before colon cancer diagnosis. Conclusions: Since diabetic patients did not have more side-effects of adjuvant chemotherapy, and adjuvant chemotherapy had a positive effect on survival for both patients with and without diabetes, diabetes alone should not be a reason for withholding adjuvant chemotherapy.Journal of Comorbidity 2011;1(1):19–2

Can vital signs recorded in patients' homes aid decision making in emergency care? A Scoping Review

Aim: Use of tele-health programs and wearable sensors that allow patients to monitor their own vital signs have been expanded in response to COVID-19. We aimed to explore the utility of patient-held data during presentation as medical emergencies. Methods: We undertook a systematic scoping review of two groups of studies: studies using non-invasive vital sign monitoring in patients with chronic diseases aimed at preventing unscheduled reviews in primary care, hospitalization or emergency department visits and studies using vital sign measurements from wearable sensors for decision making by clinicians on presentation of these patients as emergencies. Only studies that described a comparator or control group were included. Studies limited to inpatient use of devices were excluded. Results: The initial search resulted in 896 references for screening, nine more studies were identified through searches of references. 26 studies fulfilled inclusion and exclusion criteria and were further analyzed. The majority of studies were from telehealth programs of patients with congestive heart failure or Chronic Obstructive Pulmonary Disease. There was limited evidence that patient held data is currently used to risk-stratify the admission or discharge process for medical emergencies. Studies that showed impact on mortality or hospital admission rates measured vital signs at least daily. We identified no interventional study using commercially available sensors in watches or smart phones. Conclusions: Further research is needed to determine utility of patient held monitoring devices to guide management of acute medical emergencies at the patients’ home, on presentation to hospital and after discharge back to the community

Development and Internal Validation of a Multivariable Prediction Model for Adrenocortical-Carcinoma-Specific Mortality

Adrenocortical carcinoma (ACC) has an incidence of about 1.0 per million per year. In general, survival of patients with ACC is limited. Predicting survival outcome at time of diagnosis is a clinical challenge. The aim of this study was to develop and internally validate a clinical prediction model for ACC-specific mortality. Data for this retrospective cohort study were obtained from the nine centers of the Dutch Adrenal Network (DAN). Patients who presented with ACC between 1 January 2004 and 31 October 2013 were included. We used multivariable Cox proportional hazards regression to compute the coefficients for the prediction model. Backward stepwise elimination was performed to derive a more parsimonious model. The performance of the initial prediction model was quantified by measures of model fit, discriminative ability, and calibration. We undertook an internal validation step to counteract the possible overfitting of our model. A total of 160 patients were included in the cohort. The median survival time was 35 months, and interquartile range (IQR) 50.7 months. The multivariable modeling yielded a prediction model that included age, modified European Network for the Study of Adrenal Tumors (mENSAT) stage, and radical resection. The c-statistic was 0.77 (95% Confidence Interval: 0.72, 0.81), indicating good predictive performance. We developed a clinical prediction model for ACC-specific mortality. ACC mortality can be estimated using a relatively simple clinical prediction model with good discriminative ability and calibration

Influence of Receptor Polymorphisms on the Response to alpha-Adrenergic Receptor Blockers in Pheochromocytoma Patients

Background: Presurgical treatment with an α-adrenergic receptor blocker is recommended to antagonize the catecholamine-induced α-adrenergic receptor mediated vasoconstriction in patients with pheochromocytoma or sympathetic paraganglioma (PPGL). There is, however, a considerable interindividual variation in the dose-response relationship regarding the magnitude of blood pressure reduction or the occurrence of side effects. We hypothesized that genetically determined differences in α-adrenergic receptor activity contribute to this variability in dose-response relationship. Methods: Thirty-one single-nucleotide polymorphisms (SNPs) of the α1A, α1B, α1D adrenoreceptor (ADRA1A, ADRA1B, ADRA1D) and α2A, α2B adrenoreceptor (ADRA2A, ADRA2B) genes were genotyped in a group of 116 participants of the PRESCRIPT study. Haplotypes were constructed after determining linkage disequilibrium blocks. Results: The ADRA1B SNP rs10515807 and the ADRA2A SNPs rs553668/rs521674 were associated with higher dosages of α-adrenergic receptor blocker (p < 0.05) and with a higher occurrence of side effects (rs10515807) (p = 0.005). Similar associations were found for haplotype block 6, which is predominantly defined by rs10515807. Conclusions: This study suggests that genetic variability of α-adrenergic receptor genes might be associated with the clinically observed variation in beneficial and adverse therapeutic drug responses to α-adrenergic receptor blockers. Further studies in larger cohorts are needed to confirm our observations

Health-Related Quality of Life in Adrenocortical Carcinoma:Development of the Disease-Specific Questionnaire ACC-QOL and Results from the PROFILES Registry

SIMPLE SUMMARY: Patients with the rare cancer adrenocortical carcinoma are exposed to many symptoms and treatment side-effects. Research on how this can affect their health-related quality of life (HRQoL) is limited, however. This article includes the first assessment of HRQoL in a population-based cohort of patients with adrenocortical carcinoma with the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire and the newly developed disease-specific additional questionnaire ACC-QOL. The ACC-QOL has good psychometric properties in terms of validity, reliability, and responsiveness. Patients diagnosed more than 5 years ago reported a relatively good HRQoL compared with the Dutch reference population, but experienced residual fatigue and emotional problems. Patients after additional surgery reported a slightly lower HRQoL due to physical limitations. Patients who had recently received mitotane or chemotherapy reported a worse HRQoL and problems in many domains. This knowledge and the new disease-specific questionnaire can aid future research, side-effect monitoring, treatment guidance, and shared decision making. ABSTRACT: We aimed to develop a disease-specific adrenocortical carcinoma (ACC) health-related quality of life (HRQoL) questionnaire (ACC-QOL) and assess HRQoL in a population-based cohort of patients with ACC. Development was in line with European Organization for Research and Treatment of Cancer (EORTC) guidelines, though not an EORTC product. In phase I and II, we identified 90 potential HRQoL issues using literature and focus groups, which were reduced to 39 by healthcare professionals. Pilot testing resulted in 28 questions, to be used alongside the EORTC QLQ-C30. In Phase III, 100 patients with ACC were asked to complete the questionnaires twice in the PROFILES registry (3-month interval, respondents: first 67, second 51). Confirmatory factor analysis demonstrated the structural validity of 26 questions with their scale structure (mitotane side-effects, hypercortisolism/hydrocortisone effects, emotional effects). Internal consistency and reliability were good (Cronbach’s alpha 0.897, Interclass correlation coefficient 0.860). Responsiveness analysis showed good discriminative ability (AUC 0.788). Patients diagnosed more than 5 years ago reported a good HRQoL compared with the Dutch reference population, but experienced residual fatigue and emotional problems. Patients who underwent recent treatment reported a lower HRQoL and problems in several domains. In conclusion, we developed an ACC-specific HRQoL questionnaire with good psychometric properties

Efficacy of alpha-Blockers on Hemodynamic Control during Pheochromocytoma Resection:A Randomized Controlled Trial

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 non-metastatic PPGL. INTERVENTION: phenoxybenzamine or doxazosin starting 2-3 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 (i.e., 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% [IQR: 4.3-20.6] in the phenoxybenzamine group compared to 12.2% [5.3-20.2] in the doxazosin group (P=0.75, 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=0.02, r=0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P=0.68). 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

Health-Related Quality of Life in Adrenocortical Carcinoma

Insight into the health-related quality of life (HRQoL) impact of adrenocortical carcinoma (ACC) is important. The disease and its treatment options potentially have an impact on HRQoL. For patients with limited survival, HRQoL research is of utmost importance. We will therefore provide an overview of HRQoL studies in patients with ACC. We found six studies that measured HRQoL in 323 patients with ACC (3 cross-sectional, 1 cohort, 2 trials), all indicating a reduced HRQoL compared to the general population. The FIRMACT trial found that HRQoL of patients with ACC was reduced compared to the general population, and that chemotherapy-mitotane further reduced HRQoL even though survival improved. Clinical aspects of the disease, including cortisol and aldosterone production and adrenal insufficiency have shown great impact on HRQoL in benign disease, even after the recovery of hormonal status. However, the impact of malignant adrenal disease and treatment options on HRQoL including adrenalectomy, radiotherapy, mitotane therapy, and chemotherapy have not been sufficiently studied in patients with ACC. Although the number of HRQoL studies in patients with ACC is limited, the existing literature does indicate that ACC has a large impact on patients' HRQoL, with disease specific aspects. Further HRQoL research in patients with ACC is essential to improve patient-centered care, preferably by using an ACC-specific HRQoL questionnaire