Project description:The underlying cause of resistant hypertension after adrenalectomy for primary hyperaldosteronism remains controversial. The objective of this study was to identify preoperative factors predictive of resistant hypertension in patients after undergoing retroperitoneoscopic adrenalectomy. Between 2003 and 2009, 124 patients with unilateral aldosterone-producing adenoma or unilateral adrenal hyperplasia underwent retroperitoneoscopic adrenalectomy at our institution. Clinical and biochemical data were reviewed retrospectively at baseline and after a median follow-up time of 59.2 ± 37.2 months. Adrenalectomy cured hypertension in 68 patients (54.8%) and 43 (34.8%) had persistent hypertension that was much easier to control after surgery, whereas 13 patients (10.4%) had continued hypertension and poor blood pressure control. Multivariate regression analysis revealed that the main determinants of postoperative cure were duration of hypertension less than 5 years [odds ratio (OR): 6.515, 95% confidence interval (CI) 2.278-10.293), number of antihypertensive medications ≤2 (OR: 2.939, 95% CI 1.254-5.235), preoperative response to spironolactone (OR: 3.405, 95% CI 1.681-6.985), the TT genotype of the CYP11B2 gene (344 C/T) (OR: 2.765, 95% CI 1.221-4.986), and the presence of adenoma rather than hyperplasia (OR: 5.274, 95% CI 2.150-8.141). The main determinants of surgical cure or control of hypertension in patients with primary hyperaldosteronism were duration of hypertension, number of antihypertensive medications, preoperative response to spironolactone, the presence of adenoma, and CYP11B2 (344 C/T) genotype. Consideration of these factors may help in the evaluation of patients for surgery and for the identification of patients with continued postoperative hypertension that may require more long-term monitoring and treatment.
Project description:ContextPrimary aldosteronism (PA) is the most common form of endocrine hypertension. According to the Endocrine Society Practice Guidelines, the diagnosis of PA requires a pathological screening test result and non-suppressible aldosterone levels during confirmatory testing. Sequential testing with more than one confirmatory test may result in discordant test results.Objective and patientsWe investigated the association of discordant results of captopril challenge test (CCT) and saline infusion test (SIT) on patient subtype classification by adrenal vein sampling (AVS) and outcome in 111 consecutive patients from the German Conn's Registry. Concordance was defined as non-suppressible aldosterone levels upon both tests, while discordance was defined as conflicting test results. Patients with unilateral disease were offered adrenalectomy (ADX). Biochemical and clinical outcomes were assessed using the PASO criteria.Results85 of 111 (77%) patients had concordant results of CCT and SIT. Although baseline characteristics were comparable between patients with concordant and discordant tests, the latter had significantly lower aldosterone levels after testing (CCT: 170 vs. 114pg/ml; SIT: 139 vs. 101pg/ml; p=0.004). In 35% of patients with discordant (n=9) and 46% of concordant test results (n=39), AVS suggested lateralized PA. In 36 of 48 cases ADX was performed. 86% of patients with discordant and 72% with concordant results had complete biochemical success.ConclusionThe use of two confirmatory tests in patients with PA results in discordant results in approximately 23% of cases. Patients having discordant confirmatory test results had a comparable rate of lateralized PA and underwent adrenalectomy with similar long-term outcome.
Project description:PurposePrimary bilateral adrenal hyperplasia (PBMAH) is associated with hypercortisolism and a heterogeneous clinical expression in terms of cortisol secretion and related comorbidities. Historically, treatment of choice was bilateral adrenalectomy (B-Adx); however, recent data suggest that unilateral adrenalectomy (U-Adx) may be an effective alternative. For the latter, factors predicting the postsurgical outcome (e.g., biochemical control) have not been identified yet.MethodsPBMAH patients undergoing U-Adx for overt Cushing's syndrome (CS) in two tertiary care centers were retrospectively analysed. Remission was defined as a normalization of urinary free cortisol (UFC) without the need for medical treatment. The potential of hCRH test as a predictor of U-Adx outcome was evaluated in a subgroup.Results23 patients were evaluated (69% females, mean age 55 years). Remission rate after U-Adx was 74% at last follow up (median 115 months from UAdx). Before U-Adx, a positive ACTH response to hCRH (Δ%ACTH increase > 50% from baseline) was associated with higher remission rates.ConclusionsThree of four patients with PBMAH are surgically cured with U-Adx. Pre-operative hCRH testing can be useful to predict long-term remission rates.
Project description:ImportanceIn addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects.ObjectiveTo evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism.Design, setting, and participantsA cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded.Main outcomes and measuresClinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery.ResultsOn the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P < .001) and 3 (15) mm Hg (P = .04), respectively. Also, the number of antihypertensive medications used decreased from 3 (range, 0-7) to 2 (range, 0-6) (P < .001). Moreover, in 75 of 182 patients (41.2%) within this subgroup, the decrease in systolic BP was 10 mm Hg or greater.Conclusions and relevanceIn this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.
Project description:PurposeThe indications for adrenalectomy and feasibility of laparoscopic adrenalectomy for adrenal metastasis are controversial. This study aimed to compare the surgical outcomes between open adrenalectomy (OA) and laparoscopic adrenalectomy (LA) and to evaluate the prognostic factors for oncological outcomes of adrenal metastasis.Materials and methodsWe conducted a retrospective chart review of 141 consecutive patients who underwent adrenalectomy for adrenal metastasis at Seoul National University Hospital from April 2005 to February 2021. Surgical and oncological outcomes were compared between OA and LA.ResultsOA was performed in 95 (67.4%) patients, and 46 (32.6%) patients underwent LA. Among the patients who underwent adrenalectomy without adjacent organ resection for adrenal tumors less than 8 cm, LA was associated with a shorter operation time (100.1 ± 48.8 vs. 158.6 ± 81.2, P = 0.001), less blood loss (94.8 ± 93.8 vs. 566.8 ± 1156.0, P = 0.034), and a shorter hospital stay (3.7 ± 1.3 vs. 6.9 ± 5.8, P = 0.003). For locoregional recurrence-free survival (LRRFS), on multivariate analysis, a positive pathological margin (hazard ratio [HR]: 5.777, P = 0.002), disease activity at the primary site (HR: 6.497, P = 0.005), other metastases (HR: 4.154, P = 0.015), and a relatively larger tumor size (HR: 1.198, P = 0.018) were significantly associated with poor LRRFS. Multivariate analysis indicated that metachronous metastasis (HR: 0.51, P = 0.032) was associated with a longer overall survival (OS), whereas a positive pathological margin (HR: 2.40, P = 0.017), metastases to other organs (HR: 2.08, P = 0.025), and a relatively larger tumor size (HR: 1.11, P = 0.046) were associated with a shorter OS.ConclusionsLA is a feasible treatment option for adrenal metastasis in selected patients. The pathological margin, metastases to other organs, and tumor size should be considered in adrenalectomy for adrenal metastasis.
Project description:BackgroundPresence of lymph node metastasis (LNM) influences prognosis and clinical decision-making in colorectal cancer. However, detection of LNM is variable and depends on a number of external factors. Deep learning has shown success in computational pathology, but has struggled to boost performance when combined with known predictors.MethodsMachine-learned features are created by clustering deep learning embeddings of small patches of tumor in colorectal cancer via k-means, and then selecting the top clusters that add predictive value to a logistic regression model when combined with known baseline clinicopathological variables. We then analyze performance of logistic regression models trained with and without these machine-learned features in combination with the baseline variables.ResultsThe machine-learned extracted features provide independent signal for the presence of LNM (AUROC: 0.638, 95% CI: [0.590, 0.683]). Furthermore, the machine-learned features add predictive value to the set of 6 clinicopathologic variables in an external validation set (likelihood ratio test, p < 0.00032; AUROC: 0.740, 95% CI: [0.701, 0.780]). A model incorporating these features can also further risk-stratify patients with and without identified metastasis (p < 0.001 for both stage II and stage III).ConclusionThis work demonstrates an effective approach to combine deep learning with established clinicopathologic factors in order to identify independently informative features associated with LNM. Further work building on these specific results may have important impact in prognostication and therapeutic decision making for LNM. Additionally, this general computational approach may prove useful in other contexts.
Project description:Primary aldosteronism (PA) is the most common form of secondary arterial hypertension, with a prevalence of approximately 20% in patients with resistant hypertension. In the last decade, somatic pathogenic variants in KCNJ5, CACNA1D, ATP1A1 and ATP2B3 genes, which are involved in maintaining intracellular ionic homeostasis and cell membrane potential, were described in aldosterone-producing adenomas (aldosteronomas). All variants in these genes lead to the activation of calcium signaling, the major trigger for aldosterone production. Genetic causes of familial hyperaldosteronism have been expanded through the report of germline pathogenic variants in KCNJ5, CACNA1H and CLCN2 genes. Moreover, PDE2A and PDE3B variants were associated with bilateral PA and increased the spectrum of genetic etiologies of PA. Of great importance, the genetic investigation of adrenal lesions guided by the CYP11B2 staining strongly changed the landscape of somatic genetic findings of PA. Furthermore, CYP11B2 staining allowed the better characterization of the aldosterone-producing adrenal lesions in unilateral PA. Aldosterone production may occur from multiple sources, such as solitary aldosteronoma or aldosterone-producing nodule (classical histopathology) or clusters of autonomous aldosterone-producing cells without apparent neoplasia denominated aldosterone-producing micronodules (non-classical histopathology). Interestingly, KCNJ5 mutational status and classical histopathology of unilateral PA (aldosteronoma) have emerged as relevant predictors of clinical and biochemical outcome, respectively. In this review, we summarize the most recent advances in the pathogenesis of PA and discuss their impact on clinical outcome.
Project description:BackgroundThe prevalence of diabetes mellitus (DM) was higher in primary aldosteronism (PA) patients. We aimed to evaluate the outcome of DM after adrenalectomy and determine the factors associated with that in PA patients.MethodsPA patients with DM (PA + DM patients) who received adrenalectomy were recruited into the study. The patients were classified into 3 groups based on their DM conditions after treatment, including "remission", "improved" and "unchanged" groups. Univariate and multivariate logistic regression analysis was conducted to uncover the preoperative factors affecting the outcome of DM after adrenalectomy.ResultsA total of 54 PA + DM patients received adrenalectomy. After adrenalectomy, 16.7%, 33.3% and 50.0% of patients were classified into the "remission", "improved" and "unchanged" groups, respectively. The factors negatively associated with remission or improvement from DM after adrenalectomy were longer duration of hypertension (P = 0.029). Higher concentration of urinary magnesium (P = 0.031) and higher 24 h urinary potassium (P = 0.049) were factors negatively associated with the "remission" from DM after adrenalectomy.ConclusionsAdrenalectomy was beneficial for the remission and improvement from DM in the half of PA patients with DM. Longer duration of hypertension, higher concentration of urinary magnesium and higher 24 h urinary potassium may prevent the remission and improvement from DM after adrenalectomy in PA patients. Examination of urinary electrolyte could be considered in PA patients with DM for predicting the outcome of DM after adrenalectomy.
Project description:Twenty-five primary retinoblastoma tumours were analysed by real-time quantitative polymerase chain reaction to determine the genomic copy number of the N-MYC gene (2p24) relative to the copy number for REL, B2M, ALB, AF10 and MLL. Twenty-one of these tumours were shown by Comparative Genomic Hybridization to contain variable copy number increases of chromosomal material mapping to 2p. High level amplification (>30-fold) of N-MYC was found in three tumours, none of which showed adverse histological features and all patients are surviving at between 54 and 108 months post enucleation. Furthermore, the three tumours associated with metastasis and adverse patient outcome showed normal N-MYC copy number. Although high level amplification of N-MYC is an unfavourable prognostic indicator in neuroblastoma, these data show no evidence of a correlation between amplification of N-MYC and adverse outcome in retinoblastoma.