Objective: To evaluate the feasibility and accuracy of machine learning based texture analysis of unenhanced CT images in differentiating subclinical pheochromocytoma (sPHEO) from lipid-poor adenoma (LPA) in adrenal incidentaloma (AI).

Purpose Primary aldosteronism (PA) is one of the leading causes of secondary hypertension, and its diagnostic subtyping consistently presents a clinical challenge. This study aimed to investigate the potential of ⁶⁸Ga-Pentixafor PET/CT in PA classification and its applicability in guiding the development of clinical treatment plans by increasing the sample size. Methods We prospectively enrolled 120 patients with either PA or nonfunctional adenoma (NFA) for analysis. All patients underwent ⁶⁸Ga-Pentixafor PET/CT. Of these, 11 patients underwent adrenal venous sampling (AVS), 77 underwent adrenalectomy, 76 received pathological diagnoses, and 71 were subject to immunohistochemical detection of aldosterone synthase (CYP11B2). Immunohistochemistry for C-X-C chemokine receptor 4 (CXCR4) was performed in 62 cases. Follow-up was conducted for all patients. Results Among the 120 patients, 66 were diagnosed with aldosterone-producing adenoma (APA), 33 with idiopathic hyperaldosteronism (IHA), and 21 with NFA. For APA patients, the sensitivity, specificity, and accuracy of visual analysis using ⁶⁸Ga-Pentixafor PET/CT were 92.40%, 94.40%, and 93.33%, respectively. Furthermore, for APA patients with a nodule greater than 1 cm in diameter, when SUVmax ≥7.3, the specificity was 100%; and for APA patients with a nodule less than 1 cm in diameter, ⁶⁸Ga-Pentixafor PET/CT also exhibited high sensitivity. AVS was successfully performed in 5 patients. Among the 5 patients, the concordance rate between the AVS and ⁶⁸Ga-Pentixafor PET/CT for PA subtyping was 60%. In the 77 patients who underwent adrenalectomy, 61 PET/CT scans displayed positive lesions, all of which benefited from the surgery. Additionally, the concordance rate between ⁶⁸Ga-Pentixafor PET/CT imaging and CYP11B2 was 81.69%. Conclusion ⁶⁸Ga-Pentixafor PET/CT is a reliable and non-invasive functional imaging technique that demonstrates high accuracy in classifying PA and provides valuable guidance for clinical treatment decision-making.

Context Pheochromocytomas and paragangliomas (PPGLs) are characterized by distinct genotype-phenotype relationships according to studies largely restricted to Caucasian populations. Objective To assess for possible differences in genetic landscapes and genotype-phenotype relationships of PPGLs in Chinese versus European populations. Design Cross-sectional study. Setting Two tertiary-care centers in China and nine in Europe. Participants Patients with pathologically-confirmed diagnosis of PPGL, including 719 from China and 919 Europeans. Main Outcome Measures Next generation sequencing performed in tumor specimens with mutations confirmed by Sanger sequencing and tested in peripheral blood if available. Frequencies of mutations were examined according to tumor location and catecholamine biochemical phenotypes. Results Among all patients, higher frequencies of HRAS, FGFR1 and EPAS1 mutations were observed in Chinese than Europeans, whereas the reverse was observed for NF1, VHL, RET and SDHx. Among patients with apparently sporadic PPGLs, the most frequently mutated genes in Chinese were HRAS (16.5[13.6-19.3]% vs 9.8[7.6-12.1]%) and FGFR1 (9.8[7.6-12.1]% vs 2.2[1.1-3.3]%), whereas among Europeans the most frequently mutated genes were NF1 (15.9[13.2-18.6]% vs 6.6[4.7-8.5]%) and SDHx (10.7[8.4-13.0]% vs 4.2[2.6-5.7]%). Among Europeans, almost all paragangliomas lacked appreciable production of epinephrine and identified gene mutations were largely restricted to those leading to stabilization of hypoxia inducible factors. In contrast, among Chinese there was a larger proportion of epinephrine-producing paragangliomas, mostly due to HRAS and FGFR1 mutations. Conclusions This study establishes Sino-European differences in the genetic landscape and presentation of PPGLs, including ethnic differences in genotype-phenotype relationships indicating a paradigm shift in our understanding of the biology of these tumors.

Pheochromocytomas (PCCs) are rare neuroendocrine tumors that originate from chromaffin cells of the adrenal medulla, and paragangliomas (PGLs) are extra-adrenal pheochromocytomas. These can be mainly found in clinical syndromes including multiple endocrine neoplasia (MEN), von Hippel–Lindau (VHL) syndrome, neurofibromatosis-1 (NF-1) and familial paraganglioma (FPGL). PCCs and PGLs are thought to have the highest degree of heritability among human tumors, and it has been estimated that 60% of the patients have genetic abnormalities. This review provides an overview of the clinical syndrome and the genetic screening strategies of PCCs and PGLs. Comprehensive screening principles and strategies, along with specific screening based on clinical symptoms, biochemical tests and immunohistochemistry, are discussed.

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is the most common type of prostatitis. Due to the lack of a suitable animal model partly, the pathogenesis for this condition is obscure. In the current study we developed and validated an animal model for nonbacterial prostatitis and prostate inflammation-induced chronic pelvic pain in rats with the use of intraprostatic injection of λ-carrageenan. Male Sprague-Dawley rats weighing 250–350 g were used for the experiments. After intraprostatic injection of 3% λ-carrageenan, at different time points(after 24 h, 7d, 14d and 30d of injection), radiant heat and von Frey filaments were applied to the scrotum of rats to measure the heat and mechanical thresholds respectively. Then the prostate was removed for histology, and cyclooxygenase (COX) 2 protein expression was determined by Western-blot. Evans blue(50 mg/kg) was also injected intravenously to assess for plasma protein extravasation at different time points after injection of λ-carrageenan. Compared to control group, inflamed animals showed a significant reduction in mechanical threshold (mechanical allodynia) at 24 h and 7d(p = 0.022,0.046, respectively), and a significant reduction in heat threshold (thermal hyperalgesia) at 24 h, 7d and 14d(p = 0.014, 0.018, 0.002, respectively) in the scrotal skin. Significant increase of inflammatory cell accumulation,COX2 expression and Evans blue extravasation were observed at 24 h, 7d and 14d after injection. Intraprostatic λ-carrageenan injection induced neurogenic prostatitis and prostate inflammation pain, which lasted at least 2 weeks. The current model is expected to be a valuable preclinical tool to study the neurobiological mechanisms of male chronic pelvic pain.