Adrenal Pheochromocytoma Research Articles

Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs.

Low back pain is a global health problem directly related to intervertebral disc (IVD) degeneration. Senolytic drugs (RG-7112 and o-Vanillin) target and remove senescent cells from IVDs in vitro, improving tissue homeostasis. One drawback of using a single senolytic agent is the failure to target multiple senescent antiapoptotic pathways. This study aimed to determine if combining the two senolytic drugs, o-Vanillin and RG-7112, could more efficiently remove senescent cells and reduce the release of inflammatory factors and pain mediators in cells from degenerating human IVDs than either drug alone. Preliminary data evaluating multiple concentrations of o-Vanillin and RG-7112 led to the selection of four treatment groups. Monolayer and pellet cultures of cells from painful degenerate IVDs were exposed to TLR-2/6 agonist. They were then treated with the senolytics o-Vanillin and RG7112 alone or combined. p16ink4a, Ki-67, caspase-3, inflammatory mediators, and neuronal sprouting were assessed. Compared to the single treatments, the combination of o-Vanillin and RG-7112 significantly reduced the amount of senescent IVD cells, proinflammatory cytokines, and neurotrophic factors. Moreover, both single and combination treatments significantly reduced neuronal sprouting in rat adrenal pheochromocytoma (PC-12 cells). Combining o-Vanillin and RG-7112 greatly enhanced the effect of either senolytic alone. Together, these results support the potential of senolytics as a promising treatment for IVD-related low back pain.

Maternal n-7 Unsaturated Fatty Acids Protect the Fetal Brain from Neuronal Degeneration in an Intrauterine Hyperglycemic Animal Model.

We previously reported that glycation induces insulin resistance in the hearts of newborn pups from a gestational diabetes mellitus (GDM) rat model. Administration of n-3 unsaturated fatty acids suppressed glycation and improved signaling in GDM rat pups. In this study, we investigated their effects on cranial neurons using the GDM rat model and PC12 cells derived from rat adrenal pheochromocytomas. Additionally, we examined whether n-3 and n-7 unsaturated fatty acids (cis-palmitoleic acid [CPA] and trans-palmitoleic acid [TPA]) ameliorate the detrimental effects of high glucose exposure on rats. In the neonatal cerebrum of GDM rats, increased levels of advanced glycation end products (AGEs) inhibited Akt phosphorylation; however, CPA and TPA intake during pregnancy ameliorated these abnormalities. Furthermore, exposure to high-glucose-induced apoptosis in PC12 cells compared to the cells cultured in control glucose. PC12 cells exposed to high-glucose with fatty acids exhibited reduced AGE production and apoptosis induction compared to the high-glucose group. These findings suggest that a hyperglycemic environment during pregnancy promotes AGE formation in brain neuronal proteins and induces apoptosis. Both TPA and CPA mitigated these abnormalities; however, CPA is cytotoxic, highlighting its safety in pregnant women.

A CT Radiomics Analysis of the Adrenal Masses: Can We Discriminate Lipid-poor Adenomas from the Pheochromocytoma and Malignant Masses?

The aim of the study is to demonstrate a non-invasive alternative method to aid the decision making process in the management of adrenal masses. Lipid-poor adenomas constitute 30% of all adrenal adenomas. When discovered incidentally, additional dynamic adrenal examinations are required to differentiate them from an adrenal malignancy or pheochromocytoma. In this retrospective study, we aimed to discriminate lipid-poor adenomas from other lipidpoor adrenal masses by using radiomics analysis in single contrast phase CT scans. A total of 38 histologically proven lipid-poor adenomas (Group 1) and 38 cases of pheochromocytoma or malignant adrenal mass (Group 2) were included in this retrospective study. Lesions were segmented volumetrically by two independent authors, and a total of 63 sizes, shapes, and first- and second-order parameters were calculated. Among these parameters, a logit-fit model was produced by using 6 parameters selected by the LASSO (least absolute shrinkage and selection operator) regression. The model was cross-validated with LOOCV (leave-one-out crossvalidation) and 1000-bootstrap sampling. A random forest model was also generated in order to use all parameters without the risk of multicollinearity. This model was examined with the nested crossvalidation method. Sensitivity, specificity, accuracy and AUC were calculated in test sets as 84.2%, 81.6%, 82.9% and 0.829 in the logit fit model and 91%, 80%, 82.8% and 0.975 in the RF model, respectively. Predictive models based on radiomics analysis using single-phase contrast-enhanced CT can help characterize adrenal lesions.

The fourth supernumerary ovary in hepatorenal space mimicking an adrenal pheochromocytoma demonstrated with magnetic resonance imaging.

The fourth supernumerary ovary in hepatorenal space mimicking an adrenal pheochromocytoma demonstrated with magnetic resonance imaging.

An Integrated CT and MRI Imaging Model to Differentiate between Adrenal Adenomas and Pheochromocytomas.

to perform an external validation of our predictive model to rule out pheochromocytoma (PHEO) based on unenhanced CT in a cohort of patients with PHEOs and adenomas who underwent adrenalectomy. The predictive model was previously developed in a retrospective cohort of 1131 patients presenting with adrenal lesions. In the present study, we performed an external validation of the model in another cohort of 214 patients with available histopathological results. For the external validation, 115 patients with PHEOs and 99 with adenomas were included. Our previously described predictive model combining the variables of high lipid content and tumor size in unenhanced CT (AUC-ROC: 0.961) had a lower diagnostic accuracy in our current study population for the prediction of PHEO (AUC: 0.750). However, when we excluded atypical adenomas (with Hounsfield units (HU) > 10, n = 39), the diagnostic accuracy increased to 87.4%. In addition, in the whole cohort (including atypical adenomas), when MRI information was included in the model, the diagnostic accuracy increased to up to 85% when the variables tumor size, high lipid content in an unenhanced CT scan, and hyperintensity in the T2 sequence in MRI were included. The probability of PHEO was <0.3% for adrenal lesions <20 mm with >10 HU and without hyperintensity in T2. Our study confirms that our predictive model combining tumor size and lipid content has high reliability for the prediction of PHEO when atypical adrenal lesions are excluded. However, for atypical adrenal lesions with >10 HU in an unenhanced CT scan, MRI information is necessary for a proper exclusion of the PHEO diagnosis.

Pheochromocytoma/paraganglioma-associated cardiomyopathy.

Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that frequently produce and release catecholamines. Catecholamine excess can manifest in several cardiovascular syndromes, including cardiomyopathy. PPGL-induced cardiomyopathies occur in up to 11% of cases and are most often associated with an adrenal pheochromocytoma (90%) and rarely with a paraganglioma derived from the sympathetic ganglia (10%). PPGL-associated cardiomyopathies can be chronic or acute, with takotsubo cardiomyopathy being the most often reported. These two types of PPGL-induced cardiomyopathy seem to have different pathophysiological backgrounds. Acute catecholaminergic stress inundates myocardial β-adrenoceptors and leads to left ventricle stunning and slight histological apoptosis. In chronic cardiomyopathy, prolonged catecholamine exposure leads to extended myocardial fibrosis, inflammation, and necrosis, and ultimately it causes dilated cardiomyopathy with a low ejection fraction. Sometimes, especially in cases associated with hypertension, hypertrophic cardiomyopathy can develop. The prognosis appears to be worse in chronic cases with a higher hospital mortality rate, higher cardiogenic shock rate at initial presentation, and lower left ventricular recovery rate after surgery. Therefore, establishing the correct diagnosis at an early stage of a PPGL is essential. This mini-review summarizes current data on pathophysiological pathways of cardiac damage caused by catecholamines, the clinical presentation of PPGL-induced cardiomyopathies, and discusses treatment options.

Expression of Amine Oxidase Proteins in Adrenal Cortical Neoplasm and Pheochromocytoma.

We delved into the expression of amine oxidase family proteins and their potential significance in adrenal gland neoplasm. Tissue microarrays were prepared for 132 cases of adrenal cortical neoplasm (ACN) consisting of 115 cases of adrenal cortical adenoma (ACA), 17 cases of adrenal cortical carcinoma (ACC), and 163 cases of pheochromocytoma (PCC). Immunohistochemical stainings for MAOA, MAOB, LOX, and AOC3 were performed to evaluate the H-scores and compare them with clinicopathological parameters. The H-scores of MAOA (T; p = 0.005) and MAOB (T; p = 0.006) in tumor cells (T) were high in ACN, whereas LOX (T, S; p < 0.001) in tumor and stromal cells (S) and AOC3 (T; p < 0.001) were higher in PCC. In stromal cells, MAOA (S; p < 0.001) and AOC3 (S; p = 0.010) were more expressed in ACA than in ACC. MAOB (S) in PCC showed higher H-scores when the grading of adrenal pheochromocytoma and paraganglioma (GAPP) score was 3 or higher (p = 0.027). In the univariate analysis, low MAOA expression in stromal cells of ACN was associated with shorter overall survival (p = 0.008). In conclusion, monoamine oxidase proteins revealed differences in expression between ACN and PCC and also between benign and malignant cells.

Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards.

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appearances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

AMBULATORY BLOOD PRESSURE MONITORING BEFORE AND AFTER TREATMENT IN SECONDARY FORMS OF HYPERTENSION

Objective: Studies using ambulatory blood pressure (BP) monitoring (ABPM) have reported that in some secondary forms of hypertension the normal nocturnal BP decrease is blunted. Design and method: The aim of our study was to compare the nocturnal BP decrease in patients with secondary hypertension before and after treatment. ABPM was performed using the validated Meditech ABPM-06. ABPM readings were obtained at 30-minute intervals for 24-hour in patients with secondary hypertension before and after treatment. The diagnosis of secondary hypertension was based on the history and laboratory data: plasma and urinary electrolytes, renal function, calcium-phosphorus system, the renin-angiotensin-aldosterone system, urinary free cortisol, suppressibility of cortisol after 1 mg dexamethasone, plasma adrenocorticotropic hormone, plasma D4 androstenedione, plasma dehydroepiandrosterone sulphate, plasma 17-alpha hydroxyprogesterone, plasma testosterone, and urinary metanephrine. BP decrease were studied in the following groups: 42 patients with primary aldosteronism (19 men and 23 women; mean age, 44±12 years), 25 patients with adrenal pheochromocytoma (11 men and 14 women; mean age, 42±13 years), and 55 patients with Cushing's syndrome (18 men and 37 women, mean age, 43±13 years). Results: Average systolic/diastolic BP decrease was: before 2/1 mmHg and after 8/6 mmHg treatment in patients with primary aldosteronism. Average systolic/diastolic BP decrease was: before 4/5 mmHg and after 9/12 mmHg treatment in patients with adrenal pheochromocytoma. Average systolic/diastolic BP decrease was: before 3/2 mmHg and after 11/9 mmHg treatment in patients with Cushing's syndrome. All differences in systolic/diastolic BP decrease were statistically significant, with a P value &lt;.001 Conclusions: The results of our study confirm that secondary causes of hypertension lead to a reduced decrease in blood pressure during sleep. After proper treatment reduction in nighttime BP normalizes. A detailed analysis of ABPM can lead us to find the accurate etiology of hypertension.

Suprarenal Mass with Hypertension: A Diagnostic Dilemma

Suprarenal mass with hypertension points towards endocrine etiology like phaeochromocytoma,primary aldosteronism and cushing’s disease. Here we report a 50 year old female who presented with adrenal mass and hypertension. On radiology and histopathology, she was reported as having benign adrenal myelolipoma. Her pre-operative and post-operative vanillylmandelic acid in 24 hrs urine were within normal limits. Rarely adrenal myelolipoma can be associated with catecholamine secretion. This case is reported here to highlight the importance of good clinical workup when faced with the diagnostic dilemma of a functional adrenal myelolipoma or pheochromocytoma as a differential to suprarenal mass associated with hypertension along with brief review of few rare case reports.

Effect of Eleutheroside E on an MPTP-Induced Parkinson's Disease Cell Model and Its Mechanism.

This research investigated the effects of eleutheroside E (EE) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease cell model and its mechanism. Methods: To create a cell model of Parkinson's disease, MPTP (2500 μmol/L) was administered to rat adrenal pheochromocytoma cells (PC-12) to produce an MPTP group. Selegiline (50 μmol/L) and MPTP had been administered to the positive group beforehand. The eleutheroside E group was divided into low-, medium-, and high-concentration groups, in which the cells were pretreated with eleutheroside E at concentrations of 100 μmol/L, 300 μmol/L, and 500 μmol/L. Next, MPTP was added to the cells separately. The CCK-8 method was used to measure the cell survival rate. Apart from the CCK-8 method, mitochondrial membrane potential detection, cell reactive oxygen species (ROS) detection, and other methods were also adopted to verify the effect of low, medium, and high concentrations of eleutheroside E on the MPTP-induced cell model. Western blot analysis was used to detect changes in the expression of intracellular proteins CytC, Nrf2, and NQO1 to clarify the mechanism. The results are as follows. Compared with the MPTP group, the survival rates of cells at low, medium, and high concentrations of eleutheroside E all increased. The mitochondrial membrane potential at medium and high concentrations of eleutheroside E increased. The ROS levels at medium and high concentrations of eleutheroside E decreased. Moreover, the apoptosis rate decreased and the expression levels of the intracellular proteins CytC, Nrf2, and NQO1 were upregulated. Conclusion: Eleutheroside E can improve the MPTP-induced apoptosis of PC-12 cells by increasing the mitochondrial membrane potential and reducing the level of intracellular reactive oxygen species (ROS). Moreover, the apoptosis of cells is regulated by the expression of CytC, Nrf2, and NQO1 proteins.

MiR-96-5p is involved in alcohol-induced apoptosis in PC12 cells via negatively regulating TAp73.

The present study opted for the adrenal phaeochromocytoma (PC12) cell line to frame a neuronal injury model induced by alcohol exposure in vitro, aiming to probe whether TAp73 and miR-96-5p are involved in the neuronal injury process induced by alcohol and elucidate the regulatory relationship between miR-96-5p and TAp73. Immunofluorescence staining was used to observe the structural features of PC12 cells after culturing in medium with nerve growth factor (NGF). After different doses and different durations of alcohol treatment, CCK-8 assay was performed to detect the viability of PC12 cells, flow cytometry assay was carried out to detect the apoptosis rate of PC12 cells, dual-luciferase reporter assay was used to definitude the regulatory relationship between miR-96-5p and Tp73, and western blot was used to detect the protein expression of TAp73. The result of immunofluorescence staining demonstrated that PC12 cells abundantly expressed Map2, CCK-8 assay illustrated alcohol exposure significantly downregulated the cell viability of PC12 cells, Treatment with miR-96-5p inhibitor induced apoptosis and upregulated the expression of TAp73 in PC12 cells. Contrastingly, miR-96-5p mimic reversed the above effects and downregulation of TAp73 inhibited the apoptosis of PC12 cells. The present study demonstrated that miR-96-5p participates in alcohol-induced apoptosis in PC12 cells via negatively regulating TAp73.

Abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability.

There is no consensus on whether intravenous rehydration must be added after preoperative phenoxybenzamine (PXB) administration for pheochromocytoma. The aim of this study is to investigate whether abandonment of intravenous volume expansion after PXB administration is associated with intraoperative hemodynamic instability. 83 Patients with pheochromocytoma received surgical treatment in the Department of Urology, Handan First Hospital, between October 2014 and July 2022. All patients were subclassified into either the hemodynamic stability group (HS group) or the hemodynamic instability group (HU group) according to whether intraoperative hemodynamic instability occurred, with 51 cases in HS group and 32 cases in HU group. Differences in data between the two groups were examined, and the risk factors for intraoperative hemodynamic instability were analyzed using logistic regression. The results of the analysis showed no statistically significant differences in age, sex, location of the tumor, surgical method, body mass index (BMI) ≥ 24 kg/m2, blood and urine catecholamine test results, preoperative oral PXB followed by combined intravenous volume expansion, proportion of patients with hypertension or diabetes mellitus or coronary heart disease between the two groups (P>0.05). The size of the tumor in the HS group was smaller than that in the HU group (5.3 ± 1.9cm vs 6.2 ± 2.4cm P=0.010). Multivariate analyses demonstrated that abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability. Only the tumor size (P=0.025) was an independent risk factor for intraoperative hemodynamic instability. The purpose of general preoperative intravenous fluid expansion is to prevent hypotension after the tumor has been resected. In the current study, we indicated that preoperative management of pheochromocytomas using the α-blocker PXB in combination with intravenous volume expansion does not further reduce the risk of intraoperative hemodynamic instability or postoperative complications compared with oral PXB alone. Therefore, our study supports preoperative management of pheochromocytoma with a single α-blocker, PXB, as sufficient.

Surgical approaches to the adrenal gland.

Review the literature on the surgical management of adrenal diseases, highlighting the various surgical approaches and their respective pros and cons. Minimally invasive adrenalectomy is commonly used for small and benign adrenal tumors, whereas open adrenalectomy is preferred for larger tumors and primary adrenal malignancy. Although minimally invasive adrenalectomy results in shorter recovery and fewer complications compared with open, the latter offers better oncologic outcomes in the setting of primary adrenal malignancy. Adrenalectomy is performed transabdominally or retroperitoneoscopically, both yielding equivalent results and recovery. Traditional laparoscopic or robotic equipment can be utilized for either minimally invasive approach. Subtotal adrenalectomy may be appropriate for patients with genetically associated pheochromocytoma to preserve cortical function and reduce the risk of adrenal insufficiency. However, the potential benefits of sparing adrenal function must be weighed against the risk of recurrence. Adrenalectomy is becoming increasingly common worldwide. For benign and small adrenal tumors, minimally invasive adrenalectomy is generally considered the standard approach, while open adrenalectomy is preferred for primary adrenal malignancy and larger tumors. Subtotal adrenalectomy may be appropriate for patients with bilateral adrenal pheochromocytoma, as it can reduce the need for lifelong glucocorticoid dependency.

VON HIPPEL-LINDAU DISEASE, DESCRIPTION, GENETICS, MOLECULAR BASIS, CLASSIFICATION AND MANIFESTATIONS OF THE DISEASE

Introduction: Von Hippel-Lindau disease (VHL) is autosomal dominant tumor syndrome that debuts mostly in young adults , patients with this disease are linked to the triggering of various types of benign and malignant neoplasms in multiple locations, systems and organs, in particular affecting more the nervous system and other internal organs. Approximately this tumor syndrome shows an incidence rate of 1 in 36,000 live births with a penetrance greater than 90%. The molecular basis of VHL disease is the impairment of VHL protein function and the consequent clustering of hypoxia-inducible factors with subsequent consequences on cell differentiation and metabolism. Objective: to present current information related to Von Hippel-Lindau disease, description, genetics, molecular basis, classification and manifestations of the disease. Methodology: a total of 33 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 26 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: Von Hippel-Lindau, VHL, tumor suppressor gene, pheochromocytoma, hemangioblastomas. Results: VHL has an incidence of approximately 1 in 36,000 live births, with a penetrance of over 90%. These present tumors are initiated by inactivation of biallelic VHL and are related to pathologic activation of hypoxic gene response pathways. Conclusions: Von Hippel-Lindau disease is an autosomal dominant disorder that is generated by mutations in the VHL tumor suppressor gene. Within the field intrafamilial variation may evidence correctly shaped genotype-phenotype connections for renal cancer and pheochromocytoma risks. Visceral cysts (renal, pancreatic and epididymal) are frequent, however organ function involvement is rare. They usually occur with hemangioblastomas of the central nervous system and retina, as well as renal cancers. Unusually it includes non-functioning pancreatic endocrine cancers, adrenal and extra-adrenal pheochromocytomas, endolymphatic sac tumors, as well as head and neck paragangliomas. KEYWORDS: Von Hippel-Lindau, VHL, gene, suppressor, tumor, pheochromocytoma, hemangioblastomas

Abdominal nonfunctional paraganglioma in which succinate dehydrogenase subunit B (SDHB) immunostaining was performed: a case report

BackgroundAbdominal nonfunctional paraganglioma is rare. Malignant potential of paraganglioma is assessed by Grading of Adrenal Pheochromocytoma and Paraganglioma score and genetic testing, but genetic testing is not common. We present a case of abdominal nonfunctional paraganglioma whose malignant potential was assessed by grading of adrenal pheochromocytoma and paraganglioma score and succinate dehydrogenase subunit B staining alternative to genetic testing.Case presentationA 39-year-old Japanese man had a right retroperitoneal tumor without symptoms. Uptake in the tumor was shown by 123I-meta-iodobenzylguanidine scintigraphy. There were no metastases. The results of biochemical workups including blood hormones and urinary metanephrines were normal. We performed retroperitoneoscopic surgery. The tumor was positive for chromogranin A staining but negative for tyrosine hydroxylase. On the basis of the preoperative biochemical workups and pathology results, we diagnosed the tumor as nonfunctional paraganglioma. The Grading of Adrenal Pheochromocytoma and Paraganglioma score classified the tumor as moderately differentiated. Furthermore, negative succinate dehydrogenase subunit B staining suggested the patient has the SDHx (SDHA, SDHB, SDHC and SDHD) mutation.ConclusionAbdominal nonfunctional PGLs are associated with SDHB mutation, and SDHB staining should be performed as a screening.

TDP-43 is a potential marker of dopaminergic neuronal damage caused by atrazine exposure

Atrazine (ATR) is one of the herbicides widely used worldwide. Meanwhile, it is an environmental endocrine disruptor that can cross the blood-brain barrier and cause damage to the endocrine-nervous system, especially by affecting the normal secretion of dopamine (DA). Regrettably, effector markers and cascade response mechanisms in damaged dopaminergic neurons induced by ATR exposure remain elusive. In this paper, we focus on investigating aggregation and position change of transactive response DNA-binding protein-43 (TDP-43) after ATR exposure, and illustrating whether TDP-43 can serve as a potential marker of mitochondrial dysfunction which causes damage to dopaminergic neurons. In our study, we used rat adrenal pheochromocytoma cell line 12 (PC12) to establish an in vitro model of dopaminergic neurons. After PC12 was intervened by ATR, we found reduced DA cycling and DA levels, and that TDP-43 aggregated continuously in the cytoplasm and then translocated to mitochondria. Furthermore, the studies we have performed showed that the translocation can cause mitochondrial dysfunction through activating the unfolded mitochondrial protein response (UPRmt), ultimately causing damage to dopaminergic neuron. The research we have done suggests that TDP-43 can serve as a potential effector marker of dopaminergic neuron damaged caused by ATR exposure.

Preemptively planned en bloc resection of an extensive right adrenal pheochromocytoma involving the right hepatic division, caval thrombus and segmental caudal vena cava in a dog with Budd−Chiari‐like syndrome

Surgical resection is the treatment of choice for canine adrenal pheochromocytomas (PHEOs). Information on en bloc resection of adrenal PHEO with tumour thrombus, right hepatic division and segmental caudal vena cava (CVC) running through the adrenal tumour and right hepatic division is limited. To describe the preemptively planned en bloc resection of an extensive right adrenal PHEO involving the right hepatic division, the caval thrombus and the segmental CVC in a dog with Budd-Chiari-like syndrome (BCLS). A 13-year-old castrated male miniature dachshund was referred for surgical treatment due to anorexia, lethargy and severe abdominal distension caused by abundant ascites. Preoperative computed tomography (CT) revealed a large mass in the right adrenal gland with a large caval thrombus obstructing the CVC and hepatic veins, which caused BCLS. Additionally, collateral vessels were formed between the CVC and azygos veins. No findings suggested obvious metastases. Based on CT findings, an en bloc resection of the adrenal tumour with caval thrombus, right hepatic division and segmental CVC was planned. The preoperatively planned resection was feasible; the tumour was completely resected grossly. The operation time and total Pringle manoeuvre time were 162min and 16min 56 s, respectively. There was no postoperative hindlimb oedema, renal dysfunction, ascites or abdominal distention. The patient's clinical signs, including appetite, fully improved. Hospitalization lasted 16 days. However, the patient died on the 130th postoperative day due to suspected metastases and cachexia. Even in case of an extensive infiltration of adrenal PHEO causing BCLS, an en bloc resection might be successfully achieved based on the preoperative CT findings speculating the collateral vessels formed for caudal venous return.

Histogram analysis in the differentiation between adrenal adenomas and pheochromocytomas: the value of a single measurement.

To assess the diagnostic accuracy of histogram analysis on unenhanced computed tomography (CT) for differentiating between adrenal adenomas and pheochromocytomas (PCCs). We retrospectively identified patients with proven PCCs who had undergone CT examinations between January 2009 and July 2019 at one of two institutions. For each PCC, we selected one or two adenomas diagnosed within two weeks of the date of diagnosis of the PCC. For each lesion, two readers scored the size, determined the mean attenuation, and generated a voxel histogram. The 10th percentile (P10) was obtained from the conventional histogram analysis, as well as being calculated with the following formula: P10 = mean attenuation - (1.282 × standard deviation). The mean attenuation threshold, histogram analysis (observed) P10, and calculated P10 (calcP10) were compared in terms of their diagnostic accuracy. We included 52 adenomas and 29 PCCs. The sensitivity, specificity, and accuracy of the mean attenuation threshold were 75.0%, 100.0%, and 82.5%, respectively, for reader 1, whereas they were 71.5%, 100.0%, and 81.5%, respectively, for reader 2. The sensitivity, specificity, and accuracy of the observed P10 and calcP10 were equal for both readers: 90.4%, 96.5%, and 92.6%, respectively, for reader 1; and 92.3%, 93.1%, and 92.6%, respectively, for reader 2. The increase in sensitivity was significant for both readers (p = 0.009 and p = 0.005, respectively). For differentiating between adenomas and PCCs, the histogram analysis (observed P10 and calcP10) appears to outperform the mean attenuation threshold as a diagnostic criterion.

Comparison of the retroperitoneal laparoscopic adrenalectomy versus transperitoneal laparoscopic adrenalectomy for large (≥6cm) pheochromocytomas: A single-centre retrospective study.

To compare the efficacy and safety of retroperitoneal laparoscopic adrenalectomy (RLA) and transperitoneal laparoscopic adrenalectomy (TLA) in the treatment of large (≥6cm) adrenal pheochromocytomas. We retrospectively collected the clinical data of 130 patients with large pheochromocytoma who underwent RLA or TLA in our hospital from 2012 to 2022. The perioperative parameters and follow-up outcomes of the two groups were compared, and univariate and multivariate analyses were used to evaluate the risk factors of hemodynamic instability (HI). A total of 57 patients underwent TLA and 73 underwent RLA. There was no difference in demographic characteristics such as age, sex and tumor size between the two groups. Compared with the TLA group, patients in the RLA group had shorter operation time (P<0.001) and less estimated blood loss (EBL) (P<0.001). The time to ambulation, time to oral food and time to removal of drainage of RLA group were earlier than those of TLA group. In addition, the hospital stay was shorter in the RLA group than in the TLA group. There were no differences in HI, complications, or blood pressure (BP) improvement between the two groups. The mean follow-up time was 61.4 and 65.5 months, respectively, during which no tumors recurred or metastasized. Multivariate analysis showed that elevated hormone levels and larger tumor size were independent risk factors for HI. Both RLA and TLA are effective treatment methods for large pheochromocytomas, but the perioperative outcomes of RLA are better than that of TLA. Our study demonstrates the superiority of RLA for the treatment of large pheochromocytomas.