Adrenal Crisis - Definition, Prevention and Treatment: Results from a Delphi Survey.

Based on recent data, a total number of about 29 000 patients with adrenal insufficiency can be calculated for Germany, and about 1500 fatalities due to adrenal crises have to be expected within the next decade. Management of adrenal crises is still unsatisfactory. The objectives of this study were to establish consensus for diagnostic criteria, prevention strategies, and treatment recommendations for adrenal crises. The study was conducted from January 2022 to April 2023, using Delphi technique. Four rounds of questionnaires were sent to 45 experts, selected by a coordinating group on behalf of the adrenal section of the German Society of Endocrinology. The survey was implemented online using the REDCap web application. Responses were captured anonymously. During the Delphi process the expert panel developed diagnostic criteria to identify patients likely to have an adrenal crisis. Education about adrenal insufficiency among patients as well as non-endocrine medical personnel were regarded as highly important. It was suggested that recommendations for the management of adrenal insufficiency have to be simplified and made widely available. This study provides pragmatic strategies to identify and treat patients prone to adrenal crisis, thereby highlighting the need for an improved management of patients with adrenal insufficiency.

[Gastroenteropancreatic neuroendocrine tumors]. / Gastroenteropankreatische neuroendokrine Tumoren.

Neuroendocrine tumors (NET), or more generally neuroendocrine neoplasms (NEN), represent a very heterogeneous group of rare tumors with varying location which are only defined by their endocrine biology and secretion of synaptophysin and chromogranin A. They originate from mesoderm-derived stem cells. In the last few years, the incidence and prevalence of NEN have been steadily increasing. Classification is based on the affected organ, the proliferation rate and presence or absence of hormone production with typical symptoms. Diagnosis and treatment of these tumors is therefore very specific and requires an interdisciplinary approach. Treatment options include endoscopic or surgical resection, drug therapy for control of symptoms and proliferation, locoregional therapy and radionuclide therapy. Guidelines with algorithms for diagnostic workup and treatment are constantly updated.

False-positive results for pheochromocytoma associated with norepinephrine reuptake blockade.

Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a problem, particularly in patients taking norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and methoxytyramine in 61 patients taking norepinephrine reuptake blockers (tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors) and 17 others taking selective serotonin reuptake inhibitors, all without pheochromocytoma/paraganglioma. We highlight a singular case with strongly elevated plasma normetanephrine and methoxytyramine concentrations associated with norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without tumors. Plasma normetanephrine was 40% higher (P < 0.0001) in patients on norepinephrine reuptake blockers and methoxytyramine was 127% higher (P = 0.0062) in patients taking tricyclic antidepressants compared to patients not taking uptake blockers and without tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for normetanephrine and from 0.9% to 28.6% for methoxytyramine. Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma normetanephrine and methoxytyramine were elevated more than six times above upper reference limits. A pheochromocytoma/paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of norepinephrine reuptake blockers. These findings clarify that norepinephrine reuptake blockers usually result in mild elevations of normetanephrine and methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in normetanephrine and methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the norepinephrine reuptake blockade.

Bilateral subtotal thyroidectomy versus hemithyroidectomy plus subtotal resection (Dunhill procedure) for benign goiter: long-term results of a prospective, randomized study.

BACKGROUND: Two recent meta-analyses of mostly retrospective studies have shown high recurrence rates following subtotal resection of bilateral multinodular goiter. Therefore, many endocrine centers have changed their operative procedures in favor of thyroidectomy. Consequently, the rate of complications, especially hypoparathyroidism, has increased. Hemithyroidectomy plus subtotal resection (Dunhill operation) overcomes some disadvantages of bilateral subtotal resection (BST). We performed a prospective, randomized trial to compare the Dunhill operation (DO) and BST for benign goiters. METHODS: Between October 1994 and March 1997, a total of 200 consecutive patients were randomized into two study groups. Primary outcome measure was the incidence of recurrent goiter. Secondary outcome measures were incidence of recurrent nerve palsy and hypoparathyroidism. In all patients, ultrasonography of the thyroid and measurement of serum calcium and parathyroid hormone were performed. Recurrent nerve function was analyzed by indirect laryngoscopy. Long term data (>10 years after surgery) were available in 70 DO patients and 65 BST patients. Mean follow-up was 11.3 ± 4.2 years (10-12 years). RESULTS: No differences were seen in the operating times, transient and permanent hypoparathyroidism, or recurrent nerve palsy. In the long-term, mean thyroid volumes were significantly lower in the DO group (3.5 ± 3.5 vs. 6.4 ± 6.5 ml, p = 0.01). One reoperation was required in the BST group because of recurrence versus none in the DO group. 68 of 70 (97 %) patients in group DO and 59 of 65 (91 %) in group BST had ongoing thyroid hormone therapy with no significant differences in mean dosages of L-thyroxine. CONCLUSIONS: The Dunhill operation and BST are safe procedures. In case of small remnants, clinically significant recurrence is a rare event especially after the Dunhill operation.

Spectral Similarity Measures for In Vivo Human Tissue Discrimination Based on Hyperspectral Imaging.

PROBLEM: Similarity measures are widely used as an approved method for spectral discrimination or identification with their applications in different areas of scientific research. Even though a range of works have been presented, only a few showed slightly promising results for human tissue, and these were mostly focused on pathological and non-pathological tissue classification. METHODS: In this work, several spectral similarity measures on hyperspectral (HS) images of in vivo human tissue were evaluated for tissue discrimination purposes. Moreover, we introduced two new hybrid spectral measures, called SID-JM-TAN(SAM) and SID-JM-TAN(SCA). We analyzed spectral signatures obtained from 13 different human tissue types and two different materials (gauze, instruments), collected from HS images of 100 patients during surgeries. RESULTS: The quantitative results showed the reliable performance of the different similarity measures and the proposed hybrid measures for tissue discrimination purposes. The latter produced higher discrimination values, up to 6.7 times more than the classical spectral similarity measures. Moreover, an application of the similarity measures was presented to support the annotations of the HS images. We showed that the automatic checking of tissue-annotated thyroid and colon tissues was successful in 73% and 60% of the total spectra, respectively. The hybrid measures showed the highest performance. Furthermore, the automatic labeling of wrongly annotated tissues was similar for all measures, with an accuracy of up to 90%. CONCLUSION: In future work, the proposed spectral similarity measures will be integrated with tools to support physicians in annotations and tissue labeling of HS images.

Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy with an unfavorable prognosis. The impact of a locoregional lymph node dissection (LND) has never been defined in this disease. We report the disease-specific outcome of patients treated with or without LND during primary adrenalectomy. METHODS: The medical records of patients followed by the German ACC Registry were retrospectively reviewed. Patients with incomplete resection or distant metastases were excluded. Only if the histologic analysis retrieved 5 or more lymph nodes, an intended LND was assumed (LND group). The predefined primary end point of the study was disease-specific survival. RESULTS: Of 283 included patients, 47 patients (16.6%) were treated with LND, whereas 236 patients (83.4%) underwent surgery without LND. Patients who underwent LND had a larger median tumor size (12.0 cm, range: 2.3-30 cm vs 10.0 cm, range: 4.0-39 cm, P = 0.007) and were more often treated by multivisceral resection (LND: 47.8% vs no-LND: 18.1%; P < 0.001). The other baseline characteristics (age, sex, endocrine activity, Weiss score, Ki-67 index, and adjuvant treatment) did not differ significantly. Median follow-up of all patients still alive was 40 months (range: 6-326). Multivariate analysis adjusted for age, tumor stage, multivisceral resection, adjuvant treatment, and lymph nodes status on preoperative imaging demonstrated a significantly reduced risk for tumor recurrence (hazard ratio: 0.65; 95% confidence interval: 0.43-0.98; P = 0.042) and for disease-related death (hazard ratio: 0.54; 95% confidence interval: 0.29-0.99; P = 0.049) in LND patients when compared with no-LND patients. CONCLUSIONS: Our retrospective data indicate that locoregional LND improves tumor staging and leads to a favorable oncologic outcome in patients with localized ACC.

Adhesion GPCR GPR56 Expression Profiling in Human Tissues.

Despite the immense functional relevance of GPR56 (gene ADGRG1) in highly diverse (patho)physiological processes such as tumorigenesis, immune regulation, and brain development, little is known about its exact tissue localization. Here, we validated antibodies for GPR56-specific binding using cells with tagged GPR56 or eliminated ADGRG1 in immunotechniques. Using the most suitable antibody, we then established the human GPR56 tissue expression profile. Overall, ADGRG1 RNA-sequencing data of human tissues and GPR56 protein expression correlate very well. In the adult brain especially, microglia are GPR56-positive. Outside the central nervous system, GPR56 is frequently expressed in cuboidal or highly prismatic secreting epithelia. High ADGRG1 mRNA, present in the thyroid, kidney, and placenta is related to elevated GPR56 in thyrocytes, kidney tubules, and the syncytiotrophoblast, respectively. GPR56 often appears in association with secreted proteins such as pepsinogen A in gastric chief cells and insulin in islet ß-cells. In summary, GPR56 shows a broad, not cell-type restricted expression in humans.

The challenge to differentiate between sarcoma or adrenal carcinoma-an observational study.

BACKGROUND: Adrenal sarcomas are rare malignant tumors with structural and clinical similarities to sarcomatoid adrenocortical carcinoma. Preoperative diagnosis of tumors of the adrenal gland can be challenging and often misleading thus detaining patients from appropriate oncological strategies. OBJECTIVE: This analysis of a case series evaluated the predictive capability of the primary clinical diagnosis in case of malignancies of the adrenal gland. METHODS: Thirty two patients were treated from 2009 to 2015 at our clinic and analyzed retrospectively. All patients had computed tomography and/or magnet resonance imaging and a primary histopathological examination at our institution after surgery. Ten questionable cases were surveyed by a reference pathologist. RESULTS: Twelve out of 32 diagnoses had to be revised (37.5%). Only 15 out of 24 tumors primarily classified as adrenocortical carcinoma were finally described as primary adrenal cancer. We found two leiomyosarcomas, one liposarcoma, one sarcomatoid adrenocortical carcinoma, and one epitheloid angiosarcoma among 12 misleading diagnoses. Other tumors turned out to be metastases of lung, hepatocellular, and neuroendocrine tumors. Larger tumors were significantly more often correctly diagnosed compared to smaller tumors. Four patients of the group of revised diagnoses died whereas all patients with confirmed diagnoses survived during the follow-up. CONCLUSION: Preoperative assessment of tumors of the adrenal gland is still challenging. In case of wrong primary diagnosis, the prognosis could be impaired due to inadequate surgical procedures or insufficient preoperative oncological treatment.

Real-World Efficacy and Safety of Multi-Tyrosine Kinase Inhibitors in Radioiodine Refractory Thyroid Cancer.

Background: The management of patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that is refractory to radioiodine (RAI) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. Patients and Methods: We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers. One hundred and one patients with locally advanced or metastatic RAI-refractory DTC treated with sorafenib, lenvatinib, and/or pazopanib were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated by using the Kaplan-Meier method. Results: Ninety-seven of 101 patients had progressive disease before TKI initiation. The median PFS for first-line treatment with sorafenib (n = 33), lenvatinib (n = 53), and pazopanib (n = 15) was 9 (95% confidence interval 5.2-12.8), 12 (4.4-19.6), and 12 months (4.4-19.6), respectively. The median OS for first-line treatment was 37 (10-64) for sorafenib, 47 (15.5-78.5) for lenvatinib, and 34 months (20.2-47.8) for pazopanib. Serious complications (e.g., hemorrhage, acute coronary syndrome, and thrombosis/venous thromboembolism) occurred in 16 out of 75 (21%) patients taking lenvatinib, in 3 out of 42 (7%) patients taking sorafenib, and in 3 out of 24 (13%) patients taking pazopanib. Conclusions: Sorafenib, lenvatinib, and pazopanib are effective treatment options in the majority of patients with RAI-refractory DTC. The PFS and six-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favorably with sorafenib in the first-line treatment setting. However, a more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era before TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.

Curcumin attenuates oxidative stress and inflammatory response in the early phase after partial hepatectomy with simultaneous intraabdominal infection in rats.

BACKGROUND: Curcumin is a nontoxic, hepatoprotective antioxidant. It has been shown to efficiently scavenge oxygen free radicals, increase intracellular glutathione concentrations, and prevent lipid peroxidation in rat hepatocytes. Moreover, it has strong anti-inflammatory effects. In the present study we assessed its effect in a model of liver regeneration impaired by bacterial infections. MATERIAL AND METHODS: Male Sprague-Dawley rats underwent sham operation, cecal ligation and puncture (CLP), synchronous partial hepatectomy (PH), and CLP or synchronous PH+CLP with perioperative application of curcumin (100 mg per kg bodyweight per d) 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver function was analyzed by measuring the serum albumin, serum bilirubin, and bile production. The local inflammatory response in the liver tissue was evaluated by quantification of TNF-alpha, IL-6 mRNA, and quantification of IL-1beta by ELISA. In addition, hepatic concentrations of reduced glutathione (GSH) and the oxidized disulfide dimer of glutathione (GSSG) were measured for determination of the redox state. RESULTS: After simultaneous PH+CLP curcumin significantly reduced the expression of TNF-alpha and IL-6 mRNA in the liver tissue. The IL-1beta concentration in the liver was also slightly, but not significantly, lower in the curcumin group. A severe depletion of hepatic glutathione was found in the PH+CLP group. This was reversed by curcumin application, after which the GSH to GSSG ratio increased markedly. The hepatocellular damage, measured by ALT liberation, was significantly lower in the curcumin treated group. The relative liver weight in the curcumin group was significantly higher 24 h after PH+CLP. However, hepatocellular proliferation parameters were not significantly improved by antioxidative treatment with curcumin. Only the Ki-67 index was slightly higher in the curcumin treated PH+CLP group (14+/-3%) than in the untreated PH+CLP group (7%+/-3%). The hepatocyte density was significantly lower in the curcumin group than in the corresponding untreated group. CONCLUSION: In the present model, curcumin revealed significant hepatoprotective effects with stabilization of redox state, reduced liberation of liver enzymes, and attenuated expression of pro-inflammatory cytokines. However, the hepatocellular proliferation was not significantly influenced.

Influence of Parathyroidectomy on Kidney Graft Function in Secondary and Tertiary Hyperparathyroidism.

BACKGROUND: Timing of parathyroidectomy (PTX) remains controversial in candidates for kidney transplant with concomitant renal hyperparathyroidism (HPT). The aim of this retrospective study was to identify the influence of early vs late posttransplant PTX compared to pretransplant PTX on renal graft function and morbidity. METHODS: This single-center cohort study includes 57 patients with renal HPT and kidney transplantation treated between 2007 and 2017. Ninety-six patients had surgery for renal HPT between 2007 and 2017 as a consecutive sample. Group 1 (n = 30; tertiary HPT), group 2 (n = 66; secondary HPT). Of group 1, 4 patients were excluded for PTX before and after kidney transplantation. In group 2, 20 patients were excluded since they had not undergone kidney transplantation during follow-up. Twelve patients were excluded because of short follow-up (kidney transplantation in 2018), and 3 patients were excluded because of transplant failure within 90 days. Twenty-six patients underwent posttransplant PTX (10 patients within 12 months after transplant), and 31 patients had undergone PTX prior to kidney transplantation. Graft function, serum calcium concentrations, parathyroid hormone (PTH) levels, postoperative morbidity, and 90-day mortality were recorded. RESULTS: Median age was 53.1 years in group 1 and 49.1 years in group 2. Most patients were male (53.8% in group 1; 54.8% in group 2). Median preoperative PTH levels were significantly different with 331.6 pg/mL in group 1 and 667.5 pg/mL in group 2 (P = .003). Creatinine levels changed little from 1.4 mg/dL (range, 0.8-2.5) to 1.7 mg/dL (range, 0.7-7.3) in group 1, and no difference was seen between early or late PTX after transplantation. In group 2, creatinine levels were 8.5 mg/dL (range, 4.6-11.7) before PTX and 8.7 mg/dL (range, 5.1-11.9) after PTX. We saw no correlation between postoperative PTH and kidney function. Thirty-five patients with postoperative PTH < 15 pg/mL displayed a mean postoperative creatinine of 5.5 mg/dL (range, 4.3-6.8), similar to other patients. Both the 30-day and 90-day mortality rates were zero. CONCLUSIONS: PTX had no negative effect on graft function, whether performed before or after (early or late) kidney transplantation. Surgical cure of renal HPT should be performed as soon as possible to prevent secondary complications and can also be safely carried out early after transplantation.

Prospective evaluation of aldosterone LC-MS/MS-specific cutoffs for the saline infusion test.

OBJECTIVE: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has become state of the art for the quantitative analysis of steroid hormones. Although method comparisons show that aldosterone measurement using LC-MS/MS yields considerably lower levels than immunoassays (IAs), method-specific cutoff values for primary aldosteronism (PA) are largely missing. Objective of this study was to analyze the diagnostic accuracy of proposed LC-MS/MS-specific cutoff values for the saline infusion test (SIT). DESIGN AND METHODS: From 2016 to 2019, 104 consecutive patients suspected of PA underwent the SIT and captopril challenge test in the tertiary medical center at the University Hospital of Leipzig, Germany. Patients with positive case confirmation underwent adrenal imaging and adrenal venous sampling for subtype classification. RESULTS: Overall, proposed assay-specific PACLC-MS/MS cutoff values for the SIT achieved higher diagnostic accuracy than established PACIA values with a sensitivity and specificity of 87.5% (95% CI: 71.0-96.5) and 97% (95% CI: 89.6-99.6) for a cutoff of 120 pmol/L and 93.8% (95% CI: 79.2-99.2) and 92.5% (95% CI: 83.4-97.5) for a cutoff of 94 pmol/L. The most accurate post-SIT PACLC-MS/MS cutoff value in this study was 83 pmol/L, yielding a sensitivity and specificity of 96.9% (95% CI: 83.8-99.9) and 92.5% (95% CI: 83.4-97.5), respectively. CONCLUSIONS: The present data confirm the need for the implication of lower method-specific aldosterone cutoff values for the diagnosis of PA with LC-MS/MS based aldosterone measurement.

Classification of hyperspectral endocrine tissue images using support vector machines.

BACKGROUND: Thyroidectomy is one of the most commonly performed surgical procedures. The region of the neck has a very complex structural organization. It would be beneficial to introduce a tool that can assist the surgeon in tissue discrimination during the procedure. One such solution is the noninvasive and contactless technique, called hyperspectral imaging (HSI). METHODS: To interpret the HSI data, we implemented a supervised classification method to automatically discriminate the parathyroid, the thyroid, and the recurrent laryngeal nerve from surrounding tissue(muscle, skin) and materials (instruments, gauze). A leave-one-patient-out cross-validation was performed. RESULTS: The best performance was obtained using support vector machine (SVM) with a classification and visualization in less than 1.4 seconds. A mean patient accuracy of 68% ± 23% was obtained for all tissues and material types. CONCLUSIONS: The proposed method showed promising results and have to be confirmed on a larger cohort of patient data.

Prebiotics, probiotics, synbiotics in surgery--are they only trendy, truly effective or even dangerous?

BACKGROUND: Despite advances in surgical technique and intensive care medicine, nosocomial bacterial infections frequently occur in patients after major abdominal surgery and have a negative impact on operative outcome and hospital costs. In parallel, the routine use of antibiotics led to the development of resistance. Some probiotics (living bacteria) and prebiotics (fibers) are able to stabilize the intestinal barrier and prevent bacterial translocation and infections. The aim of this article was to review all available experience with pro- and prebiotics in surgical trials. MATERIALS AND METHODS: Medical databases were searched for animal trials and randomized controlled studies with pro- and prebiotics in surgical patients. Primary endpoint of all reported studies was the occurrence of bacterial infections. In addition, type and concentration of the pro- and prebiotics, duration of therapy, adverse events, and other effects were investigated. RESULTS: In three animal trials and in ten of the 15 clinical studies, probiotics or synbiotics led to a significant reduction of bacterial infection rates compared to the control groups. In two studies, there was a positive trend in the groups with synbiotics, but the results were not statistically significant. Two studies showed no effect, and in one study, the mortality rate was even higher in the synbiotic group. Except in the latter study, no severe adverse events were observed. The success of treatment depends on the synbiotic preparation and the length of therapy. Patients after surgery of the liver and pancreas and multiple trauma patients profited most from synbiotic treatment. CONCLUSION: The existing randomized controlled trials demonstrated a positive effect of synbiotics in patients with high-risk operations; however, synbiotic preparations should be extensively tested before using them in clinical trials.

Serum levels of interleukin-1 receptor antagonist (IL-1ra) in thyroid cancer patients.

BACKGROUND AND AIMS: There is growing evidence that cytokines and their antagonists are important in the pathogenesis of various malignancies. While there are several reports on interleukin-1 receptor antagonist (IL-1ra) gene polymorphism and tissue expression, there is only little data available on the impact of IL-1ra serum levels. Therefore, we performed a prospective study, analyzing IL-1ra in thyroid cancer patients. MATERIALS AND METHODS: We measured preoperative IL-1ra serum levels of 52 consecutive patients with thyroid cancer, 15 with benign adenoma and 27 healthy volunteers. The final histological diagnosis revealed 21 patients with papillary and 8 patients with follicular carcinoma (FTC), while 12 cases of medullary and 11 cases of anaplastic carcinoma (ATC) were observed. RESULTS: Compared to the control group, serum concentrations of IL-1ra were significantly higher in ATC and FTC patients. Concerning gender differences, this effect reached significance only in women with ATC and FTC. Except for the stage IV disease in ATC, there was no correlation between IL-1ra levels and International Union Against Cancer staging. CONCLUSION: The findings of our study indicate that IL-1ra may play an important role in the development of ATC and FTC. Future efforts should focus on the possible application of IL-1ra as a biomarker for the above-mentioned thyroid malignancies.

Synergistic effect of erythropoietin but not G-CSF in combination with curcumin on impaired liver regeneration in rats.

INTRODUCTION: The effect of erythropoietin (Epo) and granulocyte colony-stimulating factor (G-CSF) alone or in combination with the hepatoprotective antioxidant curcumin (Cur) was evaluated in a model of delayed liver regeneration. MATERIALS AND METHODS: Sprague Dawley rats underwent 70% liver resection with simultaneous cecal ligation and puncture and were randomised to five groups: no treatment, G-CSF (100 microg/kg), Epo (1,000 IU/kg), each alone or in combination with Cur (100mg/kg). Twenty-four hours after surgery, blood and tissue samples were collected. Markers of liver regeneration (liver weight, mitotic index, Ki-67 index), function (bilirubin, bile flow) and hepatocellular damage (liver enzymes, histomorphology) were determined. In addition, cytokine expression and hepatic glutathione concentrations were measured. RESULTS: Liver regeneration was not improved by G-CSF or Epo monotherapy. Epo more effectively increased liver weight and regeneration markers, but the difference was not significant. Whereas liver regeneration was slightly inhibited in the G-CSF plus Cur group, Epo plus Cur significantly improved liver regeneration. This was accompanied by reduced oxidative stress. Liver function and the expression of pro-inflammatory cytokines were comparable in all treatment groups. CONCLUSION: In the present model, Epo, at a relatively low dosage, did not improve liver regeneration. However, the combination of Epo and Cur showed a synergistic effect with highly significant stimulation of liver regeneration.

Adrenal Metastasis of Hepatocellular Carcinoma in Patients following Liver Resection or Liver Transplantation: Experience from a Tertiary Referral Center.

INTRODUCTION: Adrenal metastasis of hepatocellular carcinoma (HCC) is a rare entity and can be treated by resection, local ablative therapy, or systemic therapy. Unfortunately, data about treatment outcome, especially in liver transplant recipients, are rare. PATIENTS AND METHODS: From 2005 to 2015, 990 liver resections and 303 liver transplantations because of HCC were performed at our clinic. We retrospectively analyzed treatment outcome of the patients with metachronous adrenal metastasis of HCC, who received either resection, local ablation, or surveillance only. RESULTS: 10 patients were identified (0.8%). 7 patients received liver transplantation for primary HCC therapy, 3 liver resection, and 1 a local ablative therapy. 8 patients underwent adrenalectomy (one via retroperitoneoscopy), one was treated with local ablation, and one had surveillance only. Seven out of eight patients had no surgical complications and one experienced a pancreatic fistula, treated conservatively. 37.5% of the resected patients had recurrence 1 year after adrenalectomy and 75% after 2 years. The mean survival time after primary diagnosis of HCC was 96.6±22.4 months. After adrenalectomy, the mean survival time was 112.4±25.2 months. The mean time until tumor recurrence was 13.2±3.8 in the total cohort and 15.8±3.8 months in patients after adrenalectomy. The estimated overall survival after adrenalectomy was 77.2±17.4 months. CONCLUSION: Metachronous adrenal metastasis occured in less than 1% of HCC patients. Adrenalectomy is a safe procedure and leads to acceptable survival rates even after liver transplantion. Therefore, it should be performed whenever the primary tumor is well controlled and the patient is in adequate physical condition.

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma.

Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with increased morbidity and mortality compared with hypertensive controls. The central diagnostic challenge is the differentiation between bilateral and unilateral disease, which determines treatment options. Bilateral adrenal venous sampling, currently recommended for differential diagnosis, is an invasive procedure with several drawbacks, making it desirable to develop novel noninvasive diagnostic tools. When investigating the expression pattern of chemokine receptors by quantitative real-time polymerase chain reaction and immunohistochemistry, we observed high expression of CXCR4 (CXC chemokine receptor type 4) in aldosterone-producing tissue in normal adrenals, adjacent adrenal cortex from adrenocortical adenomas, and in aldosterone-producing adenomas (APA), correlating strongly with the expression of CYP11B2 (aldosterone synthase). In contrast, CXCR4 was not detected in the majority of nonfunctioning adenomas that are frequently found coincidently. The specific CXCR4 ligand 68Ga-pentixafor has recently been established as radiotracer for molecular imaging of CXCR4 expression and showed strong and specific binding to cryosections of APAs in our study. We further investigated 9 patients with primary aldosteronism because of APA by 68Ga-pentixafor-positron emission tomography. The tracer uptake was significantly higher on the side of increased adrenocortical aldosterone secretion in patients with APAs compared with patients investigated by 68Ga-pentixafor-positron emission tomography for other causes. Molecular imaging of aldosterone-producing tissue by a CXCR4-specific ligand may, therefore, be a highly promising tool for noninvasive characterization of patients with APAs.