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Annali Italiani Di Chirurgia 2024We present a case of adrenocortical adenoma originating from the adrenohepatic fusion (AHF) region, accompanied by advanced hepatosteatosis in the liver tissue, and...
We present a case of adrenocortical adenoma originating from the adrenohepatic fusion (AHF) region, accompanied by advanced hepatosteatosis in the liver tissue, and discuss its distinction from hepatocellular carcinoma. Case Experience: A 68-year-old male patient was admitted to the hospital following a fall from a height. He was referred to our hospital after an incidental discovery of a liver mass during an abdominal ultrasound examination. Subsequently, magnetic resonance imaging (MRI) imaging was conducted, followed by segmental liver resection with right adrenalectomy, and histological analysis of a biopsy from the lesion. Results: Upon histologic examination, the case was determined to be an adrenocortical adenoma originating from the AHF. Discussion: Adrenohepatic fusion (AHF) denotes the histological amalgamation of cells from the right adrenal cortex and right hepatic parenchyma. Only a limited number of cases of neoplasia originating from this region have been documented. These rare instances often present a diagnostic challenge, with preoperative imaging frequently misidentifying them as primary malignancies of either hepatic or adrenal origin, potentially leading to unnecessary extensive resections. The integration of immunohistochemical staining alongside clinical and radiological data proves helpful for accurately diagnosing this condition. Conclusion: Awareness among clinicians, radiologists, and pathologists regarding the tumors that may arise from this region can mitigate the risk of performing extensive resections unnecessarily.
Topics: Male; Humans; Aged; Adrenocortical Adenoma; Carcinoma, Hepatocellular; Adrenal Cortex Neoplasms; Liver Neoplasms
PubMed: 38469607
DOI: No ID Found -
World Journal of Surgery Jan 2024Adrenocortical carcinoma (ACC) is a notoriously aggressive cancer with a dismal prognosis, especially for patients with metastatic disease. Metastatic ACC is classically...
INTRODUCTION
Adrenocortical carcinoma (ACC) is a notoriously aggressive cancer with a dismal prognosis, especially for patients with metastatic disease. Metastatic ACC is classically a contraindication to operative management. Here, we evaluate the impact of primary tumor resection and metastasectomy on survival in metastatic ACC.
METHODS
We performed a retrospective cohort study of patients with metastatic ACC (2010-2019) utilizing the National Cancer Database. The primary outcome was overall survival (OS). Cox proportional hazards models were developed to evaluate the associations between surgical management and survival. Propensity score matching (PSM) was utilized to account for selection bias in receipt of surgery.
RESULTS
Of 976 subjects with metastatic ACC, 38% underwent surgical management. Median OS across all patients was 7.6 months. On multivariable Cox proportional hazards regression, primary tumor resection alone (HR: 0.523; p<0.001) and primary resection with metastasectomy (HR: 0.372; p<0.001) were significantly associated with improved OS. Metastasectomy alone had no association with OS (HR: 0.909; p=0.740). Primary resection with metastasectomy was associated with improved OS over resection of the primary tumor alone (HR: 0.636; p=0.018). After PSM, resection of the primary tumor alone remained associated with improved OS (HR 0.593; p<0.001), and metastasectomy alone had no survival benefit (HR 0.709; p=0.196) compared with non-operative management; combined resection was associated with improved OS over primary tumor resection alone (HR 0.575, p=0.008).
CONCLUSION
In metastatic ACC, patients may benefit from primary tumor resection alone or in combination with metastasectomy, however further research is required to facilitate appropriate patient selection.
Topics: Humans; Adrenocortical Carcinoma; Adrenal Cortex Neoplasms; Retrospective Studies; Prognosis; Proportional Hazards Models; Metastasectomy; Survival Rate
PubMed: 38463201
DOI: 10.1002/wjs.12014 -
Presse Medicale (Paris, France : 1983) Jun 2024
Topics: Humans; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Tomography, X-Ray Computed; Female; Middle Aged; Male
PubMed: 38458314
DOI: 10.1016/j.lpm.2024.104230 -
Abdominal Radiology (New York) May 2024To evaluate the diagnostic performance of multiphase hepatic CT parameters (non-contrast attenuation, absolute and relative washout ratios [APW and RPW, respectively],...
PURPOSE
To evaluate the diagnostic performance of multiphase hepatic CT parameters (non-contrast attenuation, absolute and relative washout ratios [APW and RPW, respectively], and relative enhancement ratio [RER]) and chemical-shift MRI (CS-MRI) for discriminating lipid-poor adrenal adenomas (with non-contrast CT attenuation > 10 HU) from metastases in patients with hepatocellular carcinoma (HCC).
METHODS
This retrospective study included HCC patients with lipid-poor adrenal lesions who underwent multiphase hepatic CT between January 2010 and December 2021. For each adrenal lesion, non-contrast attenuation, APW, RPW, RER, and signal-intensity index (SI-index) were measured. Each parameter was compared between adenomas and metastases. The area under the receiver operating characteristic curves (AUCs) and sensitivities to achieve 100% specificity for adenoma diagnoses were determined.
RESULTS
104 HCC patients (78 men; mean age, 71.8 ± 9.6 years) with 63 adenomas and 48 metastases were identified; CS-MRI was performed in 66 patients with 49 adenomas and 21 metastases within one year of CT. Lipid-poor adenomas showed lower non-contrast attenuation (22.9 ± 7.1 vs. 37.9 ± 9.4 HU) and higher APW (40.5% ± 12.8% vs. 23.7% ± 17.4%), RPW (30.0% ± 10.2% vs. 12.4% ± 9.6%), RER (329% ± 152% vs. 111% ± 43.0%), and SI-index (43.3 ± 20.7 vs. 10.8 ± 13.4) than HCC metastases (all p < .001). AUC for non-contrast attenuation, APW, RPW, RER, and SI-index were 0.894, 0.786, 0.904, 0.969, and 0.902, respectively. The sensitivities to achieve 100% specificity were 7.9%, 25.4%, 30.2%, 63.5%, and 24.5%, respectively. Combined RER and APW achieved the highest sensitivity of 73.0%.
CONCLUSION
Multiphase hepatic CT allows for better discrimination between lipid-poor adrenal adenomas and metastases relative to CS-MRI, especially when combined with RER and washout parameters.
Topics: Humans; Liver Neoplasms; Male; Female; Carcinoma, Hepatocellular; Retrospective Studies; Aged; Magnetic Resonance Imaging; Adrenal Gland Neoplasms; Tomography, X-Ray Computed; Diagnosis, Differential; Sensitivity and Specificity; Middle Aged; Adenoma; Contrast Media
PubMed: 38456897
DOI: 10.1007/s00261-024-04228-5 -
Cureus Feb 2024Sarcomatoid carcinoma of the adrenal gland represents an exceedingly unusual and highly aggressive form of adrenocortical carcinoma. Its diagnosis is challenging because...
Sarcomatoid carcinoma of the adrenal gland represents an exceedingly unusual and highly aggressive form of adrenocortical carcinoma. Its diagnosis is challenging because of its dual histological components: epithelial and sarcomatoid. Most patients are diagnosed at a late stage and die within months of diagnosis. We report on a 51-year-old man who had adrenocortical sarcomatoid cancer. It was diagnosed as a unilateral left adrenal incidentaloma discovered on a CT scan carried out for abdominal pain. By means of this case, we will present the clinical, radiological, and histological profile of this tumor.
PubMed: 38455785
DOI: 10.7759/cureus.53720 -
Cancer Research Communications Mar 2024Current treatment options for metastatic adrenocortical carcinoma (ACC) have limited efficacy, despite the common use of mitotane and cytotoxic agents. This study aimed...
UNLABELLED
Current treatment options for metastatic adrenocortical carcinoma (ACC) have limited efficacy, despite the common use of mitotane and cytotoxic agents. This study aimed to identify novel therapeutic options for ACC. An extensive drug screen was conducted to identify compounds with potential activity against ACC cell lines. We further investigated the mechanism of action of the identified compound, TAK-243, its synergistic effects with current ACC therapeutics, and its efficacy in ACC models including patient-derived organoids and mouse xenografts. TAK-243, a clinical ubiquitin-activating enzyme (UAE) inhibitor, showed potent activity in ACC cell lines. TAK-243 inhibited protein ubiquitination in ACC cells, leading to the accumulation of free ubiquitin, activation of the unfolded protein response, and induction of apoptosis. TAK-243 was found to be effluxed out of cells by MDR1, a drug efflux pump, and did not require Schlafen 11 (SLFN11) expression for its activity. Combination of TAK-243 with current ACC therapies (e.g., mitotane, etoposide, cisplatin) produced synergistic or additive effects. In addition, TAK-243 was highly synergistic with BCL2 inhibitors (Navitoclax and Venetoclax) in preclinical ACC models including patient-derived organoids. The tumor suppressive effects of TAK-243 and its synergistic effects with Venetoclax were further confirmed in a mouse xenograft model. These findings provide preclinical evidence to support the initiation of a clinical trial of TAK-243 in patients with advanced-stage ACC. TAK-243 is a promising potential treatment option for ACC, either as monotherapy or in combination with existing therapies or BCL2 inhibitors.
SIGNIFICANCE
ACC is a rare endocrine cancer with poor prognosis and limited therapeutic options. We report that TAK-243 is active alone and in combination with currently used therapies and with BCL2 and mTOR inhibitors in ACC preclinical models. Our results suggest implementation of TAK-243 in clinical trials for patients with advanced and metastatic ACC.
Topics: Humans; Animals; Mice; Adrenocortical Carcinoma; Mitotane; Heterografts; Ubiquitin-Activating Enzymes; Adrenal Cortex Neoplasms; Cell Line, Tumor; Antineoplastic Agents; Organoids; Proto-Oncogene Proteins c-bcl-2; Nuclear Proteins; Bridged Bicyclo Compounds, Heterocyclic; Sulfides; Sulfonamides; Pyrimidines; Pyrazoles
PubMed: 38451783
DOI: 10.1158/2767-9764.CRC-24-0085 -
European Journal of Endocrinology Mar 2024Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant...
OBJECTIVE
Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. The aim of the study was to investigate the role of circulating cell-free DNA (ccfDNA)-related biomarkers (BMs) for prognostication and monitoring of ACC.
DESIGN AND METHODS
We investigated 34 patients with ACC and 23 healthy subjects (HSs) as controls. Circulating cell-free DNA was extracted by commercial kits and ccfDNA concentrations were quantified by fluorimeter (BM1). Targeted sequencing was performed using a customized panel of 27 ACC-specific genes. Leucocyte DNA was used to discriminate somatic variants (BM2), while tumour DNA was sequenced in 22/34 cases for comparison. Serial ccfDNA samples were collected during follow-up in 19 ACC patients (median period 9 months) and analysed in relationship with standard radiological imaging.
RESULTS
Circulating cell-free DNA concentrations were higher in ACC than HS (mean ± SD, 1.15 ± 1.56 vs 0.05 ± 0.05 ng/µL, P < .0001), 96% of them being above the cut-off of 0.146 ng/µL (mean HS + 2 SD, positive BM1). At ccfDNA sequencing, 47% of ACC showed at least 1 somatic mutation (positive BM2). A combined ccfDNA-BM score was strongly associated with both progression-free and overall survival (hazard ratio [HR] = 2.63; 95% CI, 1.13-6.13; P = .010, and HR = 5.98; 95% CI, 2.29-15.6; P = .0001, respectively). During disease monitoring, positive BM2 showed the best specificity (100%) and sensitivity (67%) to detect ACC recurrence or progress compared with BM1.
CONCLUSION
ccfDNA-related BMs are frequently detected in ACC patients and represent a promising, minimally invasive tool to predict clinical outcome and complement surveillance imaging. Our findings will be validated in a larger cohort of ACCs with long-term follow-up.
Topics: Humans; Adrenocortical Carcinoma; Cell-Free Nucleic Acids; Biomarkers; DNA; Adrenal Cortex Neoplasms; Biomarkers, Tumor
PubMed: 38451242
DOI: 10.1093/ejendo/lvae022 -
World Journal of Gastrointestinal... Feb 2024B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At...
BACKGROUND
B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear.
AIM
To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC.
METHODS
The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells.
RESULTS
In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells.
CONCLUSION
B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.
PubMed: 38425404
DOI: 10.4251/wjgo.v16.i2.475 -
Microbiology Spectrum Apr 2024A landmark study by Poore et al. showed intratumor bacteria (ITBs) playing a critical role in most cancers by reproduction of The Cancer Genome Atlas (TCGA)...
UNLABELLED
A landmark study by Poore et al. showed intratumor bacteria (ITBs) playing a critical role in most cancers by reproduction of The Cancer Genome Atlas (TCGA) transcriptome data. A recent study by Salzberg et al. argued that ITBs, being overstated as a methodology by Poore et al., were problematic. We previously reported that ITBs were prognostic in adrenocortical carcinoma (ACC), a highly aggressive rare disease using data by Poore et al., and here, we aimed to answer whether ITBs truly existed and were prognostic in ACC. ACC samples from our institutes underwent 16S rRNA sequencing [adrenocortical carcinoma blocks from Huashan Hospital and China Medical University (HS) cohort]. The ITB profile was compared to TCGA data processed by Poore et al. (TCGA-P) and TCGA data processed by Salzberg et al. (TCGA-S), respectively. The primary outcome was overall survival (OS). A total of 26 ACC cases (HS cohort) and 10 paraffin controls were sequenced. The TCGA cohort encompassed 77 cases. Two and four amid the top 10 abundant genera in HS cohort were not detected in TCGA-P and TCGA-S, respectively. Neither was alpha or beta diversity associated with survival nor could ACC be subtyped by ITB signature in the HS cohort. Notably, a five-genera ITB risk score (, , , , and ) for OS trained in the HS cohort was validated in both TCGA-P and TCGA-S cohorts and was independently prognostic. Whereas ITB signature on the whole may not be associated with ACC subtypes, certain ITB features are associated with prognosis, and a risk score could be generated and validated externally.
IMPORTANCE
In this report, we looked at the role of ITBs in ACC in patients with different race and sequencing platforms. We found a five-genera ITB risk score consistently predicted overall survival in all cohorts. We conclude that certain ITB features are universally pathogenic to ACC.
Topics: Humans; Adrenocortical Carcinoma; Prognosis; Adrenal Cortex Neoplasms; RNA, Ribosomal, 16S; Risk Factors; Bacteria
PubMed: 38421176
DOI: 10.1128/spectrum.03727-23 -
The Journal of Clinical Endocrinology... Feb 2024Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis in advanced stages. While therapies targeting the checkpoint molecules programmed cell...
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis in advanced stages. While therapies targeting the checkpoint molecules programmed cell death 1 (PD-1), its ligand PD-L1 and the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) have revolutionized treatment in many cancers, the results in ACC were heterogeneous. Their expression in ACC has not been systematically studied and might explain the variable response to checkpoint inhibitors. The expression of PD-1, PD-L1 and CTLA-4 was examined in 162 tumor samples from 122 ACC patients by immunohistochemistry (threshold of >1%) and correlated with tumoral T lymphocyte infiltration and clinical endpoints. Finally, uni- and multivariate analyses of progression-free and overall survival were performed. PD-1 and PD-L1 were expressed in 26.5% and 24.7% of samples, respectively, with low expression in most tumor samples (median positive cells: 2.1% and 21.7%. In contrast, CTLA-4 expression was observed in 52.5% of ACC with a median of 38.4% positive cells. Positive PD-1 expression was associated with longer progression-free survival (HR: 0.50, 95% CI 0.25-0.98, p=0.04) even after considering prognostic factors. In contrast, PD-L1 and CTLA-4 did not correlate with clinical outcome. Additionally, PD-1 and PD-L1 expression correlated significantly with the amount of CD3+, CD4+, FoxP3+ and CD8+ T cells. The heterogeneous expression of PD1, PD-L1, and CTLA-4 in this large series of well-annotated ACC samples might explain the heterogeneous results of the immunotherapies in advanced ACC. In addition, PD-1 expression is a strong prognostic biomarker that can easily be applied in routine clinical care and histopathological assessment.
PubMed: 38415841
DOI: 10.1210/clinem/dgae109