Search Results (438)

Background/Objectives: While ¹⁷⁷Lu-DOTATATE has demonstrated clinical efficacy in peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NETs), current dosing regimens do not account for potential sex-based pharmacokinetic differences. Our study systematically characterizes sex-dependent pharmacokinetic variations of ¹⁷⁷Lu-DOTATATE in preclinical models to provide the first preclinical evidence base informing future sex-stratified clinical investigations. Methods: Sex-stratified pharmacokinetic and biodistribution studies were conducted in male and female SD rats following intravenous administration of ¹⁷⁷Lu-DOTATATE at multiple dose levels: 2.86, 5.71, and 11.43 mCi/kg. Metabolic stability and renal excretion patterns were characterized. Safety assessments included acute toxicity, vascular irritation, hemolysis, and allergenicity testing. Therapeutic efficacy was evaluated exclusively in female AR42J xenograft-bearing CB-17 SCID mice. Results: Significant sex-dependent pharmacokinetic differences were observed at high (11.43 mCi/kg) and low (2.86 mCi/kg) dose levels, with females exhibiting 30–40% higher AUC and C_max values compared to males (p < 0.05). Both sexes demonstrated preferential accumulation in SSTR-expressing tissues, particularly the pancreas (females: 10.87 ± 2.51% ID/g; males: 9.10 ± 0.76% ID/g) and adrenal glands, with rapid clearance from non-target organs. Radio-HPLC analysis confirmed high metabolic stability with no detectable radiolabeled metabolites, and over 90% of radioactivity was recovered through renal excretion. Safety assessments demonstrated excellent tolerability across dose levels. In female xenograft models, treatment achieved tumor growth inhibition of 92.35–96.44% and 100% survival rate versus 10% in controls, though mid/high doses caused weight loss. Conclusions: Our study provides systematic preclinical evidence of sex-dependent pharmacokinetic differences in ¹⁷⁷Lu-DOTATATE, with females demonstrating significantly higher systemic exposure than males at specific dose levels. These findings establish the systematic preclinical evidence base for sex-dependent pharmacokinetic differences in ¹⁷⁷Lu-DOTATATE, providing a scientific rationale for incorporating sex as a stratification variable in future dosimetry-guided clinical studies. Full article

A 13-year-old, spayed female Maltese dog presented with acute collapse and profound lethargy of approximately 1 h duration. On admission, the dog was in hypovolemic shock, with severe hypotension, marked pallor, tachycardia, and hemoperitoneum identified by focused abdominal ultrasonography. Ultrasonography also revealed a ruptured hemorrhagic mass in the right retroperitoneal space. Because the patient was hemodynamically unstable and ongoing life-threatening hemorrhage was suspected, preoperative computed tomography was considered unsafe, and emergency exploratory laparotomy was performed following transfusion-based resuscitative stabilization. Intraoperatively, the lesion was found to involve the right kidney and caudate hepatic lobe. En bloc resection, including right nephrectomy, partial hepatectomy, and excision of the retroperitoneal-associated mass, was completed while preserving the right adrenal gland and adjacent major vasculature. Histopathologic and immunohistochemical evaluation supported a diagnosis of solid-pattern hemangiosarcoma, although a single primary site of origin could not be definitively assigned. The dog recovered without major perioperative complications, was discharged in stable condition, and maintained good quality of life for approximately 1 year; however, late clinical decline suspicious for recurrence or progression was not objectively confirmed. This case highlights the practical utility of focused ultrasonography, rapid surgical decision-making, and carefully planned en bloc resection for emergency hemorrhage control in a dog when advanced imaging was considered unsafe. Full article

Background and Objectives: Renal cell carcinoma (RCC) exhibits heterogeneous and sometimes unpredictable metastatic behavior, involving both common and uncommon anatomic sites. Institutional analyses of histopathologically confirmed metastatic RCC may improve diagnostic recognition and clinical awareness. This study aimed to characterize the metastatic distribution and histopathologic features of RCC diagnosed in a single tertiary center over a five-year period. Materials and Methods: A retrospective review of the pathology database of the Department of Pathology, “Pius Brînzeu” Emergency County Hospital, Timișoara, was performed to identify all histologically confirmed cases of metastatic RCC diagnosed between January 2020 and December 2024. Case identification was based on pathology reports of metastatic lesions. In a subset of cases, corresponding pathology reports of the primary renal tumor were available and reviewed. Histopathological data collected included WHO/ISUP grade, tumor necrosis, sarcomatoid and/or rhabdoid differentiation, vascular invasion, surgical margin status, tumor size, and pathological T stage (pT). Exploratory analyses were performed to assess associations between metastatic site and selected histopathological features. Results: Thirty-two cases of metastatic RCC were identified, all demonstrating clear cell morphology. The mean patient age was 62.9 years, with a marked male predominance. Among cases with available primary tumor data, high WHO/ISUP grade and adverse histopathologic features were frequently observed. The most common metastatic sites in our institution were the brain and bone, followed by the adrenal gland, lymph nodes, and liver. Less frequent metastatic involvement included the pancreas, testis, vagina, skin, and peritoneum. Exploratory analyses did not demonstrate statistically significant associations between metastatic site and tumor grade, necrosis, or sarcomatoid/rhabdoid differentiation; however, descriptive trends were observed, including the association of brain metastases with high-grade tumors and the high prevalence of tumor necrosis across metastatic sites. Conclusions: This pathology-based retrospective series highlights the broad metastatic spectrum of RCC, including both typical and rare anatomic sites. The predominance of clear cell morphology and the frequent association with adverse histopathologic features support the link between aggressive tumor biology and metastatic disease. Although no statistically significant associations were identified, the observed patterns suggest potential relationships between metastatic distribution and tumor characteristics, warranting further investigation in larger studies. Full article

Class B scavenger receptor BI splice variants (SR-BI) and BII (SR-BII) internalize lipoproteins but also bind and internalize bacteria. Their individual roles in sepsis are unknown. We overexpressed human SR-BI or BII in transgenic mice, primarily in the liver, but also in the kidney and in bone marrow-derived macrophages, and then performed cecal ligation and puncture (CLP) surgery. SR-BI and BII transgenic mice had significantly worse survival compared to WT mice. Twenty-four hours after CLP, liver injury markers and histological damage were elevated in both SR-BI and BII transgenic mice, whereas kidney damage was similar. Systemic inflammatory cytokines were markedly increased in SR-BI and BII transgenic mice; parallel increases were seen in liver mRNA expression, but not in the kidney. The highest degree of neutrophil infiltration was observed in the liver of SR-BI. Human SR-BI and BII dramatically decreased bacterial accumulation in the liver. Green fluorescent protein-labeled E. coli were efficiently phagocytosed in hepatic macrophages of SR-BI and BII transgenic mice; phagocytosis was more prominent in SR-BII transgenic mice. Finally, human SR-BI overexpression reduced systemic HDL-C levels, eliminated adrenal cortex lipid droplets, and dampened the systemic increase of corticosterone after CLP. Supplementation with glucocorticoid and mineralocorticoid improved survival in SR-BI but not in SR-BII transgenic mice after CLP. In summary, our findings suggest human SR-BI and BII overexpression contributes to higher mortality after CLP by different mechanisms: excessive inflammatory response due to adrenal insufficiency (SR-BI) or hyperactive phagocytosis (SR-BII) in the liver. Full article

Objective: This study compared fetal adrenal gland ultrasound parameters between pregnancies complicated by fetal growth restriction (FGR) diagnosed according to Delphi consensus criteria and gestational-age-matched normally grown controls, and interpreted their apparent discriminatory performance cautiously. Methods: This prospective single-center case–control study with a cross-sectional ultrasound assessment enrolled 60 singleton pregnancies (30 FGR, 30 controls) between 24 and 41 weeks’ gestation. Controls were recruited contemporaneously from the same unit and had normal fetal biometry and Doppler findings. All examinations were performed using a Voluson E8 system by a single experienced operator; operator blinding to group status was not feasible in routine clinical practice. Standard fetal biometry and Doppler indices (umbilical artery [UA] PI, middle cerebral artery [MCA] PI, uterine artery [UtA] PI) were recorded and the cerebroplacental ratio (CPR) was calculated. Fetal adrenal assessment included the total adrenal gland volume, fetal zone (FZ) width, and middle adrenal artery (MAA) Doppler PI. Results: Maternal age, body mass index, and gestational age at scan were similar between groups (p > 0.05). Compared with controls, the FGR group had higher UA PI and UtA PI and lower MCA PI and CPR (all p < 0.001). Absolute adrenal gland volume was lower in FGR (0.46 ± 0.03 vs. 0.68 ± 0.04 cm³; mean difference −0.22 cm³, 95% CI −0.24 to −0.20; p < 0.001), and FZ width was smaller (median 4.70 vs. 6.55 mm; Hodges–Lehmann shift −1.80 mm, 95% CI −2.00 to −1.70; p < 0.001). MAA PI was higher in FGR (2.44 ± 0.14 vs. 1.79 ± 0.12; mean difference 0.65, 95% CI 0.58–0.72; p < 0.001). In this selected case–control dataset, adrenal volume, FZ width, and MAA PI each showed apparent complete separation (empirical AUC = 1.00); however, these findings should be interpreted cautiously because absolute adrenal measures were not adjusted for fetal size and such performance may reflect spectrum effects in a relatively small sample. Conclusions: In pregnancies with Delphi-defined FGR, absolute fetal adrenal volume and fetal zone width were lower, and MAA PI was higher than in controls. These findings should be considered hypothesis-generating and require external validation in larger multicenter cohorts using standardized and size-adjusted measurement approaches before clinical implementation. Full article

Pluripotent stem cells (PSCs) have proven outstanding potential to revolutionize biomedical research. Specifically, their capacity to form 3D multicellular systems that recapitulate organ development and biology, known as organoids, has transformed basic and translational research. The groundbreaking technology is also being applied to the intricate hypothalamus–pituitary (HP) axes, including the target organs (such as gonads, thyroid and adrenal glands). These HP axes govern critical physiological processes, including reproduction, metabolism and stress. Here, we provide an overview of PSC-derived organoid models that are part of the HP axes, both as individual and multi-organ systems, and evaluate their culturing conditions, phenotypic characteristics, advantages, drawbacks and challenges, as well as their potential for disease modeling and therapeutic discovery. By offering this wide perspective, our review will also serve as a key resource for researchers navigating the evolving landscape of PSC-derived organoid technologies in endocrinology. Full article

Gonadotropin-releasing hormone 1 (GnRH1) and its receptor (GnRHR1) are central neuropeptides on the hypothalamic–hypophysis–gonadal (HHG) axis and play key roles in vertebrate reproduction. Although GnRH1/GnRHR1 signaling has been extensively studied in models such as mouse, rat, zebrafish, and human, knowledge from other species is limited. This work used cloning, Sanger sequencing, and qPCR to highlight the molecular structure, evolutionary history, and sex-differentiated transcription of GnRH1/GnRHR1 signaling from hamster. These findings showed that GnRH1/GnRHR1 hamster proteins exhibit a molecular evolutionary history highly similar for peptides reported in other species and with which they share a high degree of structural homology. Expression profiles indicated a GnRH1 transcript in several tissues with higher expression levels in testes, adrenals, uterus, epididymis, female hypothalamus, and Harderian glands. GnRHR1 expression levels were seen exclusively in male and female hypophysis with higher levels in female hypophysis. Expression levels showed significant differences for GnRH1 in several tissues during estrous; GnRHR1 expression during estrous was detected only in hypophysis with increased expression levels seen during metestrus and diestrus. These results suggest a highly conserved homology of GnRHR1/GnRHR1 signaling, thus highlighting its evolutionary importance. These expression levels underscore the importance of GnRHR1 as a master regulator of reproductive endocrinology and could implicate hamster peptides as potential therapeutic biological models for human endocrine diseases. Full article

The adrenal glands are central regulators of endocrine function and stress physiology, yet detailed species-specific anatomical baselines remain limited in cetaceans. This study provides a comprehensive gross, histological, morphometric, and ultrastructural characterization of the adrenal glands in 55 short-beaked common dolphins (Delphinus delphis) examined postmortem in the Canary Islands. Adrenal glands were evaluated macroscopically and microscopically, and histological corticomedullary ratios were calculated from mid-transverse sections. Associations with body length, sexual maturity, and cause-of-death category were assessed statistically. Transmission electron microscopy was used to characterize cortical and medullary cellular ultrastructure. Adrenal weight showed a positive correlation with body length. The histological corticomedullary ratio showed no lateral asymmetry but differed significantly between sexually immature and mature individuals, indicating ontogenetic remodeling of adrenal architecture. In contrast, the corticomedullary ratio did not differ significantly between adult dolphins that died from acute events and those that died following more progressive pathological conditions. Ultrastructural analysis identified characteristic steroidogenic cortical cells and two distinct chromaffin cell populations in the medulla. These findings establish the first integrated anatomical baseline for the adrenal gland in Delphinus delphis, providing essential reference data for comparative anatomy, veterinary pathology, and the interpretation of endocrine-related findings in cetaceans. Full article

Background and Clinical Significance: Bladder cancer is common, with urothelial carcinoma (UC) comprising most cases in Western countries. Metastases usually involve pelvic structures, lymph nodes, and organs such as the liver, lungs, bones, and adrenal glands. Identifying unusual metastatic sites is critical for accurate diagnosis and treatment planning. Case Presentation: A 65-year-old man with a history of high-grade (G3) UC and carcinoma in situ, previously treated with TURBT, second-look resection, and SWOG-protocol BCG, presented with a new bladder lesion (pT1). Staging CT revealed extravesical spread and a 1.5 cm pancreatic body nodule. EUS-guided biopsy confirmed metastatic UC with concordant immunohistochemistry (GATA3+), excluding primary pancreatic cancer. The patient was referred for systemic therapy with immune checkpoint inhibitors and Enfortumab Vedotin. Conclusions: This case demonstrates the rare occurrence of pancreatic metastasis from bladder UC. EUS-guided biopsy with immunohistochemistry is essential to distinguish secondary lesions from primary pancreatic tumors. Accurate diagnosis is crucial to guide systemic therapy, particularly with emerging immunotherapy and antibody–drug conjugates. Full article

Oxidative alcohol metabolism in the liver relies on sequential enzymatic reactions involving alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1), and aldehyde dehydrogenase (ALDH) isozymes. However, the circadian regulation of these enzymes, their susceptibility to genetic, environmental, and metabolic disruption, and their functional implications toward alcohol-mediated tissue injury remain incompletely defined. To address this gap, we performed a comprehensive integrative analysis of the publicly available circadian transcriptome datasets spanning genetic clock disruption, acute sleep deprivation, chronic high-fat diet feeding, and occupational shift work to systematically characterize the temporal regulation and disruption vulnerability of the major alcohol-metabolizing enzymes. Mouse tissue-cycling analyses revealed pronounced gene- and tissue-specific diurnal regulation, with Adh1 oscillating primarily in adipose tissues; Cyp2e1 and mitochondrial Aldh2 cycling broadly across kidney, aorta, lung, adrenal gland, and liver; and cytosolic Aldh1b1 being uniformly arrhythmic. In the liver, Cyp2e1 and Aldh2 exhibited robust ~24 h oscillations that peaked during the light/resting phase, while Adh1 showed inconsistent rhythmicity and Aldh1b1 remained arrhythmic. Notably, Cyp2e1 and Aldh2 rhythms persisted in Bmal1 knockout and Clock mutant livers under light–dark conditions, despite complete loss of core clock gene oscillations, yet were abolished in constant darkness, revealing that systemic zeitgeber cues can mask the loss of intrinsic clock function to maintain apparent rhythmicity in these metabolic genes. Systematic cross-paradigm comparison established a novel gene-specific vulnerability hierarchy. Aldh2 was found to be most disrupted by environmental and metabolic perturbations, with acute sleep deprivation eliminating its rhythmicity and temporal expression pattern and a Western-style high-fat diet inducing pronounced phase delays and rhythm loss relative to low-fat diet controls. Both disruptions paralleled alterations in hepatocyte nuclear factor 4α (Hnf4a), newly implicating HNF4α as a potential mediator of ALDH2 circadian instability. In humans, ALDH2 and CYP2E1 exhibited conserved but phase-inverted circadian rhythms across multiple tissues relative to mice, and, importantly, night-shift workers showed markedly dampened and phase-shifted ALDH2 rhythms in peripheral blood mononuclear cells, providing the molecular link between occupational circadian misalignment and impaired acetaldehyde detoxification. Collectively, our detailed and innovative analytical approach reveals gene- and tissue-specific circadian regulation of alcohol-metabolizing enzymes, identifies ALDH2 as uniquely vulnerable to circadian misalignment, underscores the importance of circadian timing for optimal hepatic detoxification and resistance to tissue injury, and suggests that monitoring circadian rhythms could help tailor individualized advice on alcohol consumption for shift workers and populations with irregular sleep schedules, informing precision medicine approaches for alcohol-related disorders. Full article

Objective: This study aimed to compare fetal adrenal gland volume (AGV), fetal zone (FZ) depth, and middle adrenal artery pulsatility index (MAA-PI) between pregnancies presenting with preterm labor and gestational age-matched asymptomatic controls, and to evaluate size-adjusted adrenal metrics (corrected AGV [cAGV] and fetal zone–total gland depth ratio) in relation to gestational age at delivery and neonatal outcomes. Methods: This prospective analytical cross-sectional (case–control) study included 60 singleton pregnancies (30 with preterm labor and 30 asymptomatic controls) evaluated at a tertiary perinatology unit between 24 + 0 and 36 + 6 weeks’ gestation. Transvaginal cervical length and transabdominal fetal adrenal measurements (AGV, FZ depth, and MAA-PI) were obtained at enrollment. Estimated fetal weight (EFW) at the index scan was retrieved, and corrected AGV (cAGV = AGV/EFW) and fetal zone–total gland depth ratio were calculated. Outcomes were gestational age at delivery, birthweight, Apgar scores, and neonatal intensive care unit (NICU) admission. Nonparametric group comparisons and Spearman correlations were used. Results: Gestational age at ultrasound was identical between groups (median 31 + 6 weeks). Compared with controls, the preterm labor group had shorter cervical length (12.5 vs. 33.5 mm, p < 0.001), higher AGV (1.53 vs. 1.08 cm³, p < 0.001) and FZ depth (7.45 vs. 5.30 mm, p < 0.001), and lower MAA-PI (1.11 vs. 1.46, p < 0.001). EFW at the index scan did not differ between groups (p = 0.900). Corrected AGV (cAGV) was higher in the preterm labor group (0.87 (0.76–1.06) vs. 0.59 (0.51–0.70), p < 0.001), and the fetal zone–total gland depth ratio was higher (0.328 (0.312–0.346) vs. 0.263 (0.241–0.278), p < 0.001). The preterm labor group delivered earlier (33 + 0 vs. 36 + 2 weeks, p < 0.001), had lower birthweight (1875 vs. 3188 g, p < 0.001), and more frequent NICU admission (50.0% vs. 6.7%; odds ratio 14.0, 95% CI 2.82–69.56; p < 0.001). Within the preterm labor group, gestational age at delivery correlated positively with cervical length (ρ = 0.900) and MAA-PI (ρ = 0.770) and negatively with AGV (ρ = −0.770) and FZ depth (ρ = −0.733), all p < 0.001; correlations were stronger for cAGV (ρ = −0.953, p < 0.001). Conclusions: Enlarged fetal adrenal gland volume and fetal zone depth together with reduced middle adrenal artery pulsatility index are associated with preterm labor and earlier delivery. Size-adjusted adrenal metrics (cAGV and fetal zone–total gland depth ratio) remained significantly different between groups, supporting these measures as potential adjuncts for risk stratification at presentation. Full article

Introduction: The existence of primary adrenal gland lymphoma (PAGL) has been debated due to lack of lymphoid tissue in the adrenal glands. PAGL is extremely rare, accounting for less than 1% of all types of lymphomas. The aim of this study was to analyze patients with PAGL in Polish population. Material and Methods: We retrospectively reviewed 13 adult patients with PAGL diagnosed in Polish Hematological Centers. Results: A total of 13 patients (5 women and 8 men) with PAGL were included into the study. The median age at the diagnosis was 69.1 years (range: 31–85). The most common histological type was diffuse large B-cell lymphoma (DLBCL)-12 patients, the remaining one was diagnosed with Hodgkin lymphoma (HL). In 7 patients (54%), the left adrenal gland was involved; in 3 patients (23.5%), the right adrenal gland was involved; and 3 patients (23.5%) had bilateral lymphoma. Systemic symptoms (B symptoms) were observed in 11 out of 13 patients (85%). Two patients (15%) were treated with chemotherapy alone and the remaining eleven patients (85%) with immune and chemotherapy together (85%). During the follow-up period, 11 patients died, 8 had relapsed or refractory disease (62%), and 3 patients (23%) had relapse in central nervous system (CNS). The median progression-free survival (PFS) was 14.63 months, while the median overall survival (OS) was 20.30 months. Adrenalectomy of the involved adrenal gland was associated with shorter PFS (p = 0.0165), with trend of shorter OS. Achieving complete remission (CR) after front line treatment was associated with significantly longer OS (p = 0.0239) and PFS (p = 0.0152). Conclusions: Adrenal glands are extremely rare as primary locations of extranodal lymphoma. The prognosis of PAGL is generally poor. In this study, we described demographic, clinical, and pathological characteristics as well as factors that may affect survival among these groups. So far, it is the largest polish multicenter experience describing patients with PAGL. Full article

The hypothalamic–pituitary–adrenal (HPA) axis plays a pivotal role in regulating stress responses through ACTH-stimulated glucocorticoid production. The transcriptional programmes underlying temporal adaptation to prolonged ACTH exposure and glucocorticoid feedback remain incompletely characterized. Adult male Wistar rats were subjected to acute ACTH stimulation (single injection, 1 h) to elicit an immediate transcriptional response, prolonged ACTH exposure (three injections over 36 h) as a repeated exposure, or Dexamethasone treatment (three injections over 36 h). Plasma corticosterone levels were subsequently measured using an enzyme-linked immunosorbent assay (ELISA). The adrenal transcriptome profiling was performed using Affymetrix arrays. Differentially expressed genes (DEGs; |fold change| ≥ 1.8, adjusted p < 0.05) were analyzed using limma, followed by pathway and network analyses. Acute ACTH exposure resulted in the induction of 569 DEGs (357 upregulated), including immediate-early genes (Nr4a family, AP-1 factors), cAMP-PKA-CREB signalling components, and heat shock proteins. Prolonged ACTH resulted in 98 DEGs (predominantly downregulated), including the suppression of mitochondrial genes and upregulation of Polycomb repressive complex 2 components, suggesting epigenetic transcriptional attenuation. Dexamethasone treatment yielded 75 DEGs with selective suppression of SREBP-mediated cholesterol biosynthesis and uptake pathways. Twelve genes were downregulated by both prolonged ACTH and Dexamethasone, including sterol metabolism and interferon-stimulated genes. Acute and prolonged ACTH exposure engage distinct transcriptional programmes. Acute stimulation activates immediate-early genes and stress responses, while prolonged exposure suppresses mitochondrial gene expression through transcriptional dampening mechanisms. Dexamethasone is associated with the inhibition of cholesterol metabolism via SREBP pathway suppression. These findings illuminate HPA axis adaptation and glucocorticoid-induced adrenal suppression. Full article

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, accounting for approximately 75–80% of all renal carcinomas, and is often diagnosed incidentally on abdominal imaging, such as abdominal ultrasound or CT scan. Among other types of renal cancer, ccRCC is recognized to be highly aggressive due to its metastatic potential, which leads to a poor prognosis and an increased mortality rate. The most common sites of ccRCC metastasis are the lung, lymph nodes, bone, liver, and adrenal glands. Clear cell RCC is the most frequent primary tumor associated with secondary pancreatic involvement, while overall, pancreatic metastases represent only 2–5% of all malignant pancreatic lesions. These metastases often occur many years after nephrectomy and may present as solitary or oligometastatic disease, frequently displaying a paradoxically favorable prognosis compared with other metastatic sites. The present narrative review we conducted emerged from presentations of ccRCC with pancreatic distant metastases, potentially labeled as primary pancreatic tumors on imaging studies, mimicking pancreatic neuroendocrine tumors due to the hypervascular nature of ccRCC. Four patients were investigated in our clinic for suspicious pancreatic lesions identified on CT imaging, involving both the head and body of the pancreas. The definitive diagnosis was established by performing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or fine-needle biopsy (FNB) and histopathological analysis of the collected tissue samples. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has emerged as a pivotal tool for obtaining tissue diagnosis, particularly when cross-sectional imaging is inconclusive. Through a synthesis of clinical data and literature, this article underscores the essential diagnostic role of EUS-guided tissue acquisition and its impact on therapeutic decision-making. Full article

Metastatic lesions are the most common malignant tumor of the adrenal gland. While surgery can have a favorable surgical outcome for isolated adrenal metastatic lesions, most adrenal metastases occur in the context of disseminated disease, and the overall prognosis remains poor. Although data are limited, metastatic lesions from diverse solid tumors to the adrenal gland have typically demonstrated poor response to immunotherapy, particularly immune checkpoint inhibitors with programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade. This apparent resistance to immunotherapy suggests that the adrenal gland microenvironment may be influenced by local microenvironmental factors, resulting in an organ microenvironment that is immune tolerant and permissive to tumor growth. However, the current literature on the adrenal gland immune microenvironment is limited, underscoring the need for better understanding of the immunobiology of this critical endocrine organ. Thus, the current scarcity of scientific studies on this topic is a novel opportunity to investigate and develop innovative treatment strategies for adrenal solid cancer metastases. In this literature review, we summarize the available data published on the immunobiology of the adrenal gland and the potential local immune mechanisms that may be contributing to the adrenal gland’s role in promoting resistance to otherwise breakthrough immunotherapy treatments. Full article