NF-κB1 deficiency promotes macrophage-derived adrenal tumors but decreases neurofibromas in HTLV-I LTR-Tax transgenic mice.

Human T-cell leukemia virus type I (HTLV-I) is an oncogenic virus whose infection can cause diverse diseases, most notably adult T-cell leukemia/lymphoma (ATL or ATLL), an aggressive and fatal malignancy of CD4 T cells. The oncogenic ability of HTLV-I is mostly attributed to the viral transcriptional transactivator Tax. Tax alone is sufficient to induce specific tumors in mice depending on the promotor used to drive Tax expression, thereby being used to understand HTLV-I tumorigenesis and model the tumor types developed in Tax transgenic mice. Tax exerts its oncogenic role predominantly by activating the cellular transcription factor NF-κB. Here, we report that genetic deletion of NF-κB1, the prototypic member of the NF-κB family, promotes adrenal medullary tumors but suppresses neurofibromas in mice with transgenic Tax driven by the HTLV-I Long Terminal Repeat (LTR) promoter. The adrenal tumors are derived from macrophages. Neoplastic macrophages also infiltrate the spleen and lymph nodes, causing splenomegaly and lymphadenopathy in mice. Nevertheless, the findings could be human relevant, because macrophages are important target cells of HTLV-I infection and serve as a virus reservoir in vivo. Moreover, the spleen, lymph nodes and adrenal glands are the most common sites of tumor cell infiltration in HTLV-I-infected patients. These data provide new mechanistic insights into the complex interaction between Tax and NF-κB, therefore improving our understanding of HTLV-I oncogenic pathogenesis. They also expand our knowledge and establish a new animal model of macrophage neoplasms and adrenal tumors.

Patient classification and attribute assessment based on machine learning techniques in the qualification process for surgical treatment of adrenal tumours.

Adrenal gland incidentaloma is frequently identified through computed tomography and poses a common clinical challenge. Only selected cases require surgical intervention. The primary aim of this study was to compare the effectiveness of selected machine learning (ML) techniques in proper qualifying patients for adrenalectomy and to identify the most accurate algorithm, providing a valuable tool for doctors to simplify their therapeutic decisions. The secondary aim was to assess the significance of attributes for classification accuracy. In total, clinical data were collected from 33 patients who underwent adrenalectomy. Histopathological assessments confirmed the proper selection of 21 patients for surgical intervention according to the guidelines, with accuracy reaching 64%. Statistical analysis showed that Supported Vector Machines (linear) were significantly better than the baseline (p < 0.05), with accuracy reaching 91%, and imaging features of the tumour were found to be the most crucial attributes. In summarise, ML methods may be helpful in qualifying patients for adrenalectomy.

Risk factors for postoperative fever after laparoscopic adrenalectomy focusing on hormones produced: a case control study.

BACKGROUND: Laparoscopic adrenalectomy is widely performed for a number of hormone-producing tumors and postoperative management depends on the hormones produced. In the present study, we conducted a retrospective analysis to clarify the risk factors for postoperative complications, particularly postoperative fever after laparoscopic adrenalectomy. METHODS: We analyzed 406 patients who underwent laparoscopic adrenalectomy at our hospital between 2003 and 2019. Postoperative fever was defined as a fever of 38 °C or higher within 72 h after surgery. We investigated the risk factors for postoperative fever after laparoscopic adrenalectomy. RESULTS: There were 188 males (46%) and 218 females (54%) with a median age of 52 years. Among these patients, tumor pathologies included 188 primary aldosteronism (46%), 75 Cushing syndrome (18%), and 80 pheochromocytoma (20%). Postoperative fever developed in 124 of all patients (31%), 30% of those with primary aldosteronism, 53% of those with pheochromocytoma, and 8% of those with Cushing syndrome. A multivariate logistic regression analysis identified pheochromocytoma and non-Cushing syndrome as independent predictors of postoperative fever. Postoperative fever was observed in 42 out of 80 cases of pheochromocytoma (53%), which was significantly higher than in cases of non-pheochromocytoma (82/326, 25%, p < 0.01). In contrast, postoperative fever developed in 6 out of 75 cases of Cushing syndrome (8%), which was significantly lower than in cases of non-Cushing syndrome (118/331, 35.6%, p < 0.01). CONCLUSION: Since postoperative fever after laparoscopic adrenalectomy is markedly affected by the hormone produced by pheochromocytoma and Cushing syndrome, it is important to carefully consider the need for treatment.

A 14-year-old girl with premature ovarian insufficiency but with a positive pregnancy test.

OBJECTIVES: Childhood cancer survivors are at risk for premature ovarian insufficiency, especially after treatment with alkylating agents. The objective of this report is to highlight a case in which this phenomenon caused a false-positive pregnancy test. CASE PRESENTATION: A workup was performed in a 14-year-old girl with a positive pregnancy test. She was diagnosed with stage IV neuroblastoma of the left adrenal gland at the age of 4 years. She received extensive treatment, including alkylating agents, and had been diagnosed with premature ovarian insufficiency. An LH/hCG suppression test was performed using high dose 17 bèta-estradiol: hCG levels normalized. CONCLUSIONS: The pregnancy test was false-positive due to production of low amounts of hCG by the pituitary gland as a result of high LH concentrations following premature ovarian insufficiency. It may be helpful to perform the LH/hCG suppression test to prove pituitary origin of the hCG overproduction.

Anastomosing haemangioma of adrenal gland: an unusual vascular tumour.

With only 15 reported cases, anastomosing haemangioma of adrenal is a rare entity and usually presents as adrenal incidentaloma. A hypertensive, diabetic, non-smoker man in his late 60s presented with irritative voiding symptoms. On evaluation, he was found to have a urinary bladder mass and left adrenal incidentaloma measuring 8 cm. Metabolic evaluation confirmed it to be non-functional.The patient underwent transurethral resection of bladder tumour with left laparoscopic adrenalectomy. Intraoperatively, the adrenal tumour was highly vascular with multiple feeder vessels. Grossly it was soft, encapsulated with focal grey-brown areas. Microscopically, most of adrenal gland was replaced by anastomosing proliferating capillary vessels within framework of non-endothelial supporting cells reminiscent of splenic sinusoids. The tumour was positive for CD-31, CD-34, Glut-1 and SMA.Anastomosing haemangioma is a benign entity but it must be differentiated from angiosarcoma. Characteristic imaging features are not yet defined and is, therefore, difficult to diagnose preoperatively.

Loss of tumor suppressor TMEM127 drives RET-mediated transformation through disrupted membrane dynamics.

Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumor pheochromocytoma (PCC) can be caused by activating mutations of the rearranged during transfection (RET) receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumor suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and downstream signaling, driving cell proliferation. Loss of TMEM127 altered normal cell membrane organization and recruitment and stabilization of membrane protein complexes, impaired assembly, and maturation of clathrin-coated pits, and reduced internalization and degradation of cell surface RET. In addition to RTKs, TMEM127 depletion also promoted surface accumulation of several other transmembrane proteins, suggesting it may cause global defects in surface protein activity and function. Together, our data identify TMEM127 as an important determinant of membrane organization including membrane protein diffusability and protein complex assembly and provide a novel paradigm for oncogenesis in PCC where altered membrane dynamics promotes cell surface accumulation and constitutive activity of growth factor receptors to drive aberrant signaling and promote transformation.

Clinical features and treatment options for pediatric adrenal incidentalomas: a retrospective single center study.

BACKGROUND: The aim of this study was to investigate the clinical features and treatment options for pediatric adrenal incidentalomas(AIs) to guide the diagnosis and treatment of these tumors. METHODS: The clinical data of AI patients admitted to our hospital between December 2016 and December 2022 were collected and retrospectively analyzed. All patients were divided into neonatal and nonneonatal groups according to their age at the time of the initial consultation. RESULTS: In the neonatal group, 13 patients were observed and followed up, and the masses completely disappeared in 8 patients and were significantly reduced in size in 5 patients compared with the previous findings. Four patients ultimately underwent surgery, and the postoperative pathological diagnosis was neuroblastoma in three patients and teratoma in one patient. In the nonneonatal group, there were 18 cases of benign tumors, including 9 cases of ganglioneuroma, 2 cases of adrenocortical adenoma, 2 cases of adrenal cyst, 2 cases of teratoma, 1 case of pheochromocytoma, 1 case of nerve sheath tumor, and 1 case of adrenal hemorrhage; and 20 cases of malignant tumors, including 10 cases of neuroblastoma, 9 cases of ganglioneuroblastoma, and 1 case of adrenocortical carcinoma. CONCLUSIONS: Neuroblastoma is the most common type of nonneonatal AI, and detailed laboratory investigations and imaging studies are recommended for aggressive evaluation and treatment in this population. The rate of spontaneous regression of AI is high in neonates, and close observation is feasible if the tumor is small, confined to the adrenal gland and has no distant metastasis.

Modified versus three-level technique of retroperitoneal laparoscopic adrenalectomy for all patients with adrenal lesions ≤ 6cm: a retrospective, case-controlled study.

Objectives: The modified three-level technique for retroperitoneal laparoscopic adrenalectomy (RLA) has proven beneficial in the treatment of adrenal lesions in patients with BMI≥25 Kg/m2. This paper aims to summarize our institution's seven-year experience using this technique for all patients with Adrenal Lesions ≤ 6cm. Patients and methods: Between January 2016 and December 2022. The patients underwent laparoscopic adrenal surgery were categorized into Zhang's technique (ZT) (Three-level Technique) group and modified technique (MT) group. The fundamental characteristics and perioperative data were analyzed, with statistical significance set at p<0.05. Results: In total, 731 patients were stratified into two groups: ZT (n=448) and MT (n=283). Statistically significant distinctions were not detected between the two groups regarding sex, BMI, tumor location, tumor size, tumor type, or American Society of Anesthesiologists (ASA) score (p>0.05). The MT group demonstrated superior outcomes compared to the ZT group in terms of operative time, estimated blood loss, drainage volume, diet recovery time, complication rates, and postoperative hospitalization duration (p<0.05). 17 (4.34%) in the ZT group required unplanned adrenalectomy, while there was none in MT group (P<0.05). Conclusion: MT retroperitoneal laparoscopic adrenalectomy has demonstrated its benefits in the treatment of adrenal lesions across all patients with adrenal lesions ≤ 6cm, serving as a valuable point of reference for the surgical management of adrenal diseases. Patient summary: We have made modifications to the classic retroperitoneal laparoscopic adrenalectomy and achieved superior surgical outcomes, resulting in a procedure known as modified retroperitoneal laparoscopic adrenalectomy. This technique is suitable for both obese individuals and the general population with adrenal lesions ≤ 6cm.

Clinical indications, safety, and effectiveness of percutaneous image-guided adrenal mass biopsy: an 8-year retrospective analysis in 160 patients.

PURPOSE: To assess indications, safety, and effectiveness of percutaneous adrenal mass biopsy in contemporary practice. METHODS: This institutional review board-approved, retrospective study included all patients undergoing percutaneous image-guided adrenal mass biopsies at an academic health system from January 6, 2015, to January 6, 2023. Patient demographics, biopsy indications, mass size, laboratory data, pathology results, and complications were recorded. Final diagnoses were based on pathology or ≥ 1 year of imaging follow-up when biopsy specimens did not yield malignant tissue. Test performance calculations excluded repeat biopsies. Continuous variables were compared with Student's t test, dichotomous variables with chi-squared test. RESULTS: A total of 160 patients underwent 186 biopsies. Biopsies were indicated to diagnose metastatic disease (139/186; 74.7%), for oncologic research only (27/186; 14.5%), diagnose metastatic disease and oncologic research (15/186; 8%), and diagnose an incidental adrenal mass (5/186; 2.7%). Biopsy specimens were diagnostic in 154 patients (96.3%) and non-diagnostic in 6 (3.8%). Diagnostic biopsies yielded malignant tissue (n = 136), benign adrenal tissue (n = 12), and benign adrenal neoplasms (n = 6) with sensitivity = 98.6% (136/138), specificity = 100% (16/16), positive predictive value = 100% (136/136), and negative predictive value = 88.9% (16/18). Adverse events followed 11/186 procedures (5.9%) and most minor (7/11, 63.6%). The adverse event rate was similar whether tissue was obtained for clinical or research purposes (10/144; 6.9% vs. 1/42; 2.4%, p = 0.27), despite more specimens obtained for research (5.8 vs. 3.7, p < 0.001). CONCLUSION: Percutaneous adrenal mass biopsy is safe, accurate, and utilized almost exclusively to diagnose metastatic disease or for oncologic research. The negative predictive value is high when diagnostic tissue samples are obtained. Obtaining specimens for research does not increase adverse event risk.

Differential diagnosis of rare adrenal cellular schwannomas: A case report.

BACKGROUND: Adrenal cellular schwannomas are exceptionally rare stromal tumors that are often misdiagnosed due to the lack of specific radiological, serological, or clinical features. In this report, we describe the differential diagnosis of a rare adrenal cellular schwannoma. METHODS: A 69-year-old man with a history of persistent hypertension, chronic kidney disease, hypertensive heart disease, and cardiac insufficiency was hospitalized due to bilateral lower extremity edema lasting for 3 months. Plain computed tomography at that time revealed a space-occupying lesion in the right adrenal gland. As serum levels of catecholamines, cortisol, and adrenocorticotropic hormone were within normal ranges, the edema was attributed to the chronic kidney disease and cardiac insufficiency, and the patient was referred to our hospital for surgical treatment. Contrast-enhanced computed tomography revealed heterogeneous enhancement in the adrenal mass indicating pheochromocytoma. An irregularly shaped 5 cm mass with a complete capsule in the right adrenal gland was laparoscopically resected. The postoperative histopathological diagnosis was adrenal cellular schwannoma. RESULTS: The postoperative course was unremarkable and the tumor did not recur during 5 years of follow-up. CONCLUSION: Adrenal cellular schwannoma is a very rare tumor that is extremely difficult to preoperatively diagnose. Histological and immunohistochemical analyses are required for differential diagnosis and confirmation. Cellular schwannomas can transform into malignant peripheral nerve sheath tumors, but not often. Consequently, regular postoperative follow-up is required for such patients, especially imaging.

[Xanthogranulomatous adrenalitis : A rare and difficult differential diagnosis of adrenal gland tumors]. / Xanthogranulomatöse Adrenalitis : Seltene und schwierige Differentialdiagnose von Nebennierentumoren.

A radiologically diagnosed tumor in a 29-year-old woman with a fever of around 39 °C was operated on under the suspicion of cholecystitis or a liver abscess. A solid tumor was found in the adrenal gland and resected. The frozen section findings did not reveal a clear diagnosis of entity and assignment. Histologically, the tumor was found to consist of densely clustered large histiocyte-like cells with expression of vimentin, CD68, and CD163 as well as negativity for keratin, langerin, and SMA. We diagnosed xanthogranulomatous adrenalitis and discussed the differential diagnoses (Langerhans cell histiocytosis, Rosai-Dorfman disease, malakoplakia, Erdheim-Chester disease).

PHOX2B: a diagnostic cornerstone in neurocristopathies and neuroblastomas.

Paired-like homeobox 2B (PHOX2B) is a gene essential in the development of the autonomic nervous system. PHOX2B mutations are associated with neurocristopathies-Hirschsprung disease (HSCR) and congenital central hypoventilation syndrome (CCHS)-and peripheral neuroblastic tumours. PHOXB2 plays an important role in the diagnostics of these conditions.Genotyping of a PHOX2B pathogenic variant is required to establish a diagnosis of CCHS. In HSCR patients, PHOX2B immunohistochemical staining has proven to be a valuable tool in identifying this disease. Furthermore, PHOXB2 is a predisposition gene for neuroblastoma, in which PHOX2B immunohistochemical staining can be used as a highly sensitive and specific diagnostic marker. The utility of PHOX2B immunohistochemistry in pheochromocytoma and paraganglioma has also been studied but yields conflicting results.In this review, an overview is given of PHOX2B, its associated diseases and the usefulness of PHOX2B immunohistochemistry as a diagnostic tool.

Perioperative Outcomes After Adrenalectomy for Secondary Adrenal Malignancy.

INTRODUCTION: The risk of adverse outcomes after adrenal metastasectomy is not well defined. Knowledge of these risks is essential to guide patient counseling. METHODS: The 2015-2020 National Surgical Quality Improvement Program datasets were combined. Patients who underwent adrenalectomy for secondary adrenal malignancy (SM) and benign nonfunctional (BNF) adrenal neoplasms were identified; BNF neoplasms were chosen as a comparison as functional neoplasms can contribute to comorbidity. Patients who had additional surgery at the time of adrenalectomy were excluded. Patient demographics, comorbidities, perioperative factors, and outcomes were compared between groups. Multivariable logistic regression analysis was performed. RESULTS: Of 3496 adrenalectomy patients, 332 had SM and 3164 had BNF neoplasms. Patients with SM were older (65 versus 54 y) and more often had chronic obstructive pulmonary disease (7.5% versus 4.4%), chronic steroid use (10.5% versus 3.8%), and bleeding disorders (4.5% versus 2.2%) than patients with BNF, respectively (P < 0.01 for all). Laparoscopic adrenalectomy was the most common operative approach for both groups (74.7% versus 88.3%). Rates of mortality, morbidity, reoperation, readmission, and nonhome discharge did not differ significantly between groups. Patients with SM had higher rates of postoperative bleeding than patients with BNF (6.3% versus 2.6%, P < 0.001). This persisted on multivariable regression analysis that adjusted for demographics, comorbidities, and operative approach (odds ratio 2.34, 95% confidence interval 1.19-4.64). CONCLUSIONS: Adrenalectomy for SM is associated with an increased risk of postoperative bleeding compared to adrenalectomy for BNF adrenal neoplasms. Patients with SM that meet criteria for adrenal metastasectomy should be counseled appropriately.

Exploring the Benefits of a Reduced-Port Approach in Robotic Posterior Retroperitoneoscopic Adrenalectomy: A Comparative Study of the Two-Port and Three-Port Techniques.

Background: Robotic adrenalectomy has become a surgical treatment option for benign and selected malignant adrenal diseases. We aimed to evaluate the eligibility of two-port robotic posterior retroperitoneoscopic adrenalectomy (PRA) as an alternative to the conventional three-port technique by comparing their surgical outcomes. Materials and Methods: This retrospective cohort study compared the clinicopathological factors and surgical outcomes among 197 patients who underwent two-port or three-port robotic adrenalectomy between 2016 and 2020 in a single tertiary center. For further evaluation, propensity score matching was performed to reduce the selection bias in population characteristics. Results: Patients were categorized by the number of ports (two-port group, 87; and three-port group, 110). The two-port group compared with the three-port group was significantly older (P = .006) and had a smaller mean tumor size (P = .003) and shorter mean operation time (P = .001). Upon comparing clinicopathologic characteristics according to adrenal disorders, for pheochromocytoma, the three-port group had a larger tumor size and a longer operation time. For Cushing's syndrome, the operation time was short and numeric rating scale pain score was significantly low in the two-port group. After propensity score matching, the two-port group had a short operation time and a significantly low postoperative pain score (P < .05). Predictive factors associated with prolonged operation time included male gender, an increased number of ports, and large tumor size. Conclusions: The two-port technique resulted in a shorter operation time and lower pain score compared with the three-port technique. The two-port technique may be a safe alternative to the conventional three-port technique for robotic PRA.

Impact of Body Mass Index ≥35 kg/m2 on Minimally Invasive Adrenalectomy.

Introduction: Obesity is associated with numerous chronic conditions and an increased risk for surgical complications. Laparoscopic and robotic adrenalectomy have proven effective in the resection of adrenal tumors. This study analyzes the outcomes of severely obese patients (body-mass index [BMI] ≥35 kg/m2) following minimally invasive adrenalectomy. Materials and Methods: A retrospective analysis of patients who underwent minimally invasive adrenalectomy at our institution between 2010 and 2023 was conducted. Two matching analyses were performed. The first analysis compared patients with BMI greater versus lower than 35 kg/m2. The second analysis compared outcomes between robotic and laparoscopic adrenalectomy in patients with a BMI ≥35 kg/m2. Results: A total of 278 patients were included in the study. The median tumor size was 29 mm. Adrenal tumors had similar laterality, and most were hormonally active (66.2%). The most common pathological diagnosis was pheochromocytoma (25.5%). No statistical difference was found in peri- and postoperative outcomes between patients with BMI ≥35 and <35 kg/m2 who underwent minimally invasive adrenalectomy. When the surgical approach was compared in severely obese patients, robotic adrenalectomy was associated with shorter hospital length of stay with similar operative time as the laparoscopic approach. Conclusions: Minimally invasive adrenalectomy is safe and feasible in patients with BMI ≥35 kg/m2. Robotic and laparoscopic approaches are both safe and efficient for the resection of adrenal tumors in severely obese patients.

A novel study, textbook outcome in adrenalectomy: retrospective observational study in an endocrine surgical unit.

Textbook outcome is a multidimensional quality management tool that uses a set of traditional surgical measures to reflect an "ideal" surgical result for a particular pathology. Retrospective study of all patients undergoing scheduled for adrenal tumors surgery at an endocrine surgery unit from January 2010-December 2022. The definition of Textbook Outcome were: R0 resection, no Clavien-Dindo ≥ IIIa complications, no prolonged stay (< P75), no readmissions, and no mortality in the first 30 days. The main objective was to analyze the rate of Textbook Outcome obtained. One hundred and five patients were included in the study. Textbook Outcome was achieved in 71.4%. Surgical approach (p < 0.001), Charlson scale (p = 0.031), American Society of Anesthesiologists Classification (p = 0.047) and surgical time (p < 0.001) were all significantly associated with the achievement of Textbook Outcome. The laparoscopic approach was associated as an independent factor with obtaining Textbook Outcome (OR:5.394; p = 0.016), as was surgical time (OR:0.986; p = 0.004). Textbook Outcome is a novel, useful, easy-to-interpret tool for measuring results in adrenal surgery. The laparoscopic approach is associated with a higher rate of "ideal" surgical results. The study was registered in the public accessible database clinicaltrials.gov with the ClinicalTrials.gov ID: NCT05888753.