Adrenal glands removed for unilateral primary aldosteronism (PA) display marked histological heterogeneity. Recently reported somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D can partially account for these differences. In this study we aimed at combining phenotypic and genotypic characteristics, integrating genetic and immunohistochemistry correlates in sporadic PA. Seventy-one adrenal glands have been included in the study and analyzed for mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. Histological examination and immunohistochemical staining for CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) were performed on aldosterone-producing adenomas (APAs) and adjacent adrenal cortex. In our cohort, the final histopathological diagnosis was multinodular hyperplasia in 22.5% of the patients and single nodule in 77.5%. Forty-five percent of the removed adrenals displayed extra-APA CYP11B2-positive cell nests (B2-CN). Among adrenal vein sampling parameters the suppression of contralateral adrenal was more frequent and the lateralization index was higher in the subgroup of patients without extra-APA B2-CN compared to the subgroup with extra-APA B2-CN. KCNJ5-mutated APAs were composed mainly of zona fasciculata-like cells with high expression of CYP11B1, while ATP1A1, ATP2B3 and CACNA1D-mutated APAs presented more frequently a zona-glomerulosa-like phenotype with high expression of CYP11B2. We observed a significant inverse correlation between CYP11B2 expression and the size of the nodules and, if CYP11B2 expression was corrected for tumor volume, a significant correlation with plasma aldosterone and aldosterone to renin ratio. Our findings indicate that combination of genotyping and immunohistochemistry improves the final histopathological diagnosis between single nodule and multinodular hyperplasia of the assessed adrenals.

Biliary leaks complicating hepaticojejunostomy (HJA) or fistulas from cut surface are severe complications after liver transplantation (LT) and split-liver transplantation (SLT). The aim of the study was to describe our experience about the safety and efficacy of radiological percutaneous treatment without dilatation of intrahepatic biliary ducts. From 1990 to 2006, 1595 LTs in 1463 patients were performed in our center. In 1199 LTs (75.2%), a duct-to-duct anastomosis was performed, and in 396 (24.8%), an HJA was performed. One hundred twenty-nine anastomotic or cut-surface bile leakages occurred in 115 patients. Sixty-two biliary leaks occurred in 54 patients with HJA; in 48 cases, an anastomotic fistula was found. Cut-surface fistulas occurred in 14 cases: 5 in right SLTs and 5 in left SLTs. Twenty-two patients were treated with 23 percutaneous approaches for 17 HJA fistulas and 6 cut-surface leaks without intrahepatic bile duct dilatation. Two percutaneous therapeutic approaches were used: percutaneous transhepatic biliary drainage (PTBD) for fistula alone and PTBD with percutaneous drainage of biliary collection in patients with both complications. PTBD was successful in 21 cases (91.3%); the median delay from catheter insertion and leak resolution was 10.3 days (range: 7-41). The median maintenance of drainage was 14.8 days. In 1 patient, fistula recurrence after PTBD needed a surgical approach; after that, an anastomotic fistula was still found, and a new PTBD was successfully performed. In another patient, PTBD was immediately followed by retransplantation for portal vein thrombosis. There were no complications related to the interventional procedure. In conclusion, biliary fistulas after HJA in LT or after SLT can be successfully treated by PTBD. The absence of enlarged intrahepatic biliary ducts should not be a contraindication for percutaneous treatment. Liver Transpl 14:611-615, 2008. © 2008 AASLD. Received June 26, 2007 accepted October 31, 2007. Biliary complications after liver transplantation (LT) have an incidence of 10% to 30% 1 ; reduced-size LT, split-liver transplantation (SLT), and living-donor LT are associated with increased rates of biliary complications.2 A lower rate of complications directly related to hepaticojejunostomy (HJA) versus duct-to-duct anastomosis has been described.3-5 Surgical repair and endoscopic management have been reported to successfully treat post-LT biliary fistulas from duct-to-duct anastomosis, but when the biliary leaks complicate HJA or they rise from the cut surface of the liver, an endoscopic approach is not possible. The aim of this study was to evaluate the safety and efficacy of percutaneous treatment of post-LT biliary leakages occurring in HJA or in split-liver recipients in the absence of biliary tree dilatation. PATIENTS AND METHODSFrom 1990 to 2006, 1595 LTs in 1463 patients were performed in our center; in 1199 LTs (75%), a duct-toAbbreviations: HLA, hepaticojejunostomy; LT, liver transplantation; PTBD, percutaneous transhepatic biliary drainag...

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Primary aldosteronism (PA) is now recognized as the most frequent form of secondary arterial hypertension. The importance of a correct and prompt diagnosis of PA is determined by its relevant prevalence, its increased cardiovascular risk compared to essential hypertension and by the possibility of reversing this increased risk with a targeted therapy. Surgical treatment of unilateral forms of PA (mainly aldosterone-producing adenomas) is at present recommended in well-selected patients because of its cost-effectiveness. Therefore, subtype differentiation of PA forms is of fundamental importance, and available guidelines recommend contrast-enhanced CT-scanning and adrenal venous sampling (AVS) as the main diagnostic tests for this purpose. In this review, we discuss the value of adrenal non-invasive imaging and AVS, the recent advances in complementary tests and, finally, the available data on the outcome of surgical treatment for PA.

: Aldosterone producing adenoma CYP11B1 immunohistochemistry CYP11B2 immunohistochemistry KCNJ5 ATP1A1 CACNA1D A B S T R A C T Adrenal glands removed for unilateral primary aldosteronism (PA) display marked histological heterogeneity. Recently reported somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D can partially account for these differences. In this study we aimed at combining phenotypic and genotypic characteristics, integrating genetic and immunohistochemistry correlates in sporadic PA. Seventy-one adrenal glands have been included in the study and analyzed for mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. Histological examination and immunohistochemical staining for CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) were performed on aldosterone-producing adenomas (APAs) and adjacent adrenal cortex. In our cohort, the final histopathological diagnosis was multinodular hyperplasia in 22.5% of the patients and single nodule in 77.5%. Forty-five percent of the removed adrenals displayed extra-APA CYP11B2-positive cell nests (B2-CN). Among adrenal vein sampling parameters the suppression of contralateral adrenal was more frequent and the lateralization index was higher in the subgroup of patients without extra-APA B2-CN compared to the subgroup with extra-APA B2-CN. KCNJ5-mutated APAs were composed mainly of zona fasciculata-like cells with high expression of CYP11B1, while ATP1A1, ATP2B3 and CACNA1D-mutated APAs presented more frequently a zona-glomerulosa-like phenotype with high expression of CYP11B2. We observed a significant inverse correlation between CYP11B2 expression and the size of the nodules and, if CYP11B2 expression was corrected for tumor volume, a significant correlation with plasma aldosterone and aldosterone to renin ratio. Our findings indicate that combination of genotyping and immunohistochemistry improves the final histopathological diagnosis between single nodule and multinodular hyperplasia of the assessed adrenals.