Adrenal gland cancer (AGC) is a rare cancer with a poor prognosis. Studies on this cancer have been limited. This study, for the first time, aims to analyze the global disease burden and trends of AGC in country level and examine lifestyle and socioeconomic risk factors to generate hypotheses.

The Global Cancer Observatory database was used to extract the incidence rate of AGC in 2020. Age-standardized rates (ASRs) of AGC incidence and lifestyle/metabolic risk factor prevalence were obtained from databases. Linear regression and Joinpoint regression were used to assess associations with risk factors and Average Annual Percentage Change of AGC incidence.

Globally, there were an estimated 16 961 new AGC cases in 2020 (ASR: 0.14 per 100 000 persons). Higher disease burden was observed mainly in European regions. ASRs were comparable between sexes (males: 0.16; females: 0.14). The higher ASR was observed among the older population aged 50 to 74 years with an ASR of 0.31 compared with the younger population aged 15 to 49 years with an ASR of 0.07. Higher AGC incidence was associated with higher Human Development Index, gross domestic product, and lifestyle-related factors such as physical inactivity, obesity, hypertension, and lipid disorder (β = 0.005-0.052).

The overall incidence trend showed a decrease, with 3 countries reporting significant decreases and 1 country reporting a significant increase. Similar patterns were observed by sex and age group, except for an overall increase among the younger population.

In locally advanced adrenocortical carcinoma (ACC) (ENSAT stage III - S-III) R0 surgery, involving en bloc extended resections, is the only potential curative treatment. We evaluated oncological outcomes and complications rate in S-III patients who underwent extended resection in comparison with stage I/II (S-I/II). Among 1098 adrenalectomies over 27 years (1997 -2024) in a tertiary referral center, medical records of ACC patients were reviewed, excluding stage IV and not-multivisceral resections in S-III patients. Forty-eight patients met the inclusion criteria: 6 S-I (12.5%), 36 S-II (75%) and 6 S-III (12.5%) patients. The latter patients' cohort underwent multivisceral en bloc resections (3 total nephrectomies, one renal vein thrombectomy, one splenopancreasectomy associated with total nephrectomy, left hemicolectomy and omentectomy, one liver S6-S7-S8 resection). Open adrenalectomy was scheduled in all S-III patients. Minimally-invasive approach was scheduled in 21 (50%) S-I/II patients. Conversion to open adrenalectomy was registered in 5 out these 21 patients. Locoregional and distant disease recurrences were registered in 19% of S-I/II vs 33.3% of S-III patients and 28.6% of S-I/II vs 66.7% of S-III patients, respectively (p = 0.420, p = 0.064). Postoperative complications were observed in 21.4% of S-I/II patients and 16.7% of S-III patients (p = 0.788). Kaplan-Meier DFS and OS curves were comparable among the two groups (p = 0.255, p = 0.459, respectively). After univariable analysis, hyperfunction and chemotherapy were significantly associated with locoregional disease recurrence (p = 0.02, p = 0.04, respectively). OS and DFS of S-III ACC patients undergoing extended en bloc R0 resections were comparable to those of S-I/II patients, without increased postoperative morbidity.

Production of adrenal androgens begins with cholesterol, and through a series of enzymatic steps catalyzed by the cytochrome p450 superfamily, forms several 19-carbon sex hormones. Benign disorders of adrenal androgen hypersecretion include adrenal variants of polycystic ovarian syndrome, congenital adrenal hyperplasia, and nonmalignant tumors. Adrenocortical carcinomas can also oversecrete adrenal androgens. Primary adrenal hypoandrogenism is not generally accepted as a stand-alone diagnosis in women. Blockade of adrenal androgens has emerged as contemporary treatment of men with metastatic prostate cancer. Here, we explore the history of the adrenal gland, its biosynthetic pathway, and common disorders of adrenal androgen hypersecretion and blockade.

Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of recurrence and poor prognosis. Previous studies revealed controversial roles of adjuvant radiation therapy (RT) in patient management. This study aimed to investigate the role of adjuvant RT in postoperative ACC patients.

Patients with histologically confirmed ACC who underwent surgical resection in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2020 were enrolled. Propensity score matching (PSM) was used to balance baseline characteristics between patients receiving adjuvant RT and patients who did not receive RT. Overall survival (OS) and recurrence-free survival (RFS) was analyzed using the Kaplan-Meir method. Risk factors associated with survival outcome was analyzed by univariate and multivariate Cox regression analyses. Subgroup analyses were stratified by European Network for the Study of Adrenal Tumors (ENSAT) disease stage or chemotherapy. A joint retrospective analysis of stage III patients was performed based on data obtained from Ruijin Hospital and MD Anderson Cancer Center.

Among the 700 patients enrolled, 137 patients undergoing postoperative RT were matched with 137 patients who did not receive RT. Overall survival for patients with adjuvant RT was better than patients without RT (log-rank P = 0.015). The 3-year and 5-year OS were 55.2 and 47.1% for patients with RT, vs 42.6 and 34.0% for patients without RT. Multivariate analysis showed adjuvant RT was independently associated with lower mortality (hazard ratio [HR] 0.63, P = 0.007). Subgroup analysis stratified by disease stage demonstrated that adjuvant RT showed the most favorable effect in stage III patients (HR 0.53, P = 0.013). Furthermore, joint analysis of two centers showed a tendency of better OS and local control rate for stage III patients with mitotane plus RT than those with mitotane alone.

Our study indicated that adjuvant RT was associated with improved prognosis for ACC patients, especially for patients with ENSAT stage III diseases. Integrating adjuvant RT into standard care of ACC may be considered.

Stage III adrenocortical carcinoma encompasses both lymph node positive (TanyN1M0) and negative (T3-4N0M0) disease. Given the disease's rarity, the current staging paradigm's estimates of survival are supported by limited evidence. Consequently, we examined the impact of clinical lymph node positivity on survival outcomes in the context of the current staging of advanced adrenocortical carcinoma.

We identified patients with clinical stage III and IV disease from the National Cancer Database. Kaplan-Meier methods and Cox proportional hazards models estimated overall survival for stage III lymph node negative, stage III lymph node positive, and stage IV disease.

We identified 917 patients with adrenocortical carcinoma - 322 (35.1%) stage III lymph node negative, 67 (7.3%) stage III lymph node positive, and 528 (57.6%) stage IV. 3-year overall survival for patients with stage III lymph node negative, stage III lymph node positive, and stage IV disease was 48.6%, 29.4%, and 15.6%, respectively. On univariable analysis, patients with stage III lymph node positive disease were associated with worse survival than those with stage III lymph node negative disease (HR 1.72, 95% CI 1.26-2.37, P < 0.001); however, this relationship did not maintain significance in multivariable analysis (HR 1.27, 95% CI 0.88-1.83, P = 0.21).

Our study finds that patients with clinical stage III lymph node positive adrenocortical carcinoma may have worse survival outcomes than stage III patients without lymph node involvement. The results of this study suggest the need for an updated, more nuanced staging paradigm, which differentiates stage III disease by lymph node positivity.

Adrenalectomies are growing worldwide because of the frequent diagnosis of incidentaloma and the use of minimally invasive surgery (MIS). The factors used to identify a malignant lesion and the best surgical technique are uncertain. In this context, the definition of high-volume center and expert surgeon is under debate. The Italian Society of Endoscopic Surgery and New Technologies (SICE) developed a nationwide survey to investigate the state-of-the-art of adrenal surgery in Italy. A web-based survey comprising 37 questions was developed and distributed to Italian surgeons involved in adrenal surgery. Two hundred forty-eight answers were analyzed. Consensus was reached among the survey participants regarding local infiltration (83%) and rapid growth of the lesion (81%) as markers of malignancy. Nearly 30% of the participants used MIS in case of malignant adrenal lesions. The lateral (50%) and anterior transperitoneal (44%) approaches were the most common among Italian surgeons. Approximately 40% of participants believe that 20-40 adrenalectomies/year are needed to define an expert surgeon and at least 20 procedures/year to define a high-volume center. Approximately half of participants performed < 10 adrenalectomies/year in centers with a median volume < 10 procedures/year. Based on participant feedback, this survey highlights local infiltration and rapid growth as the most significant markers of malignant adrenal lesions. While open adrenalectomy remains the gold standard for suspected malignant lesions, nearly 30% of the participants practice MIS even in these cases. The lateral and anterior transperitoneal approaches emerge as the most familiar for Italian surgeons. A substantial proportion of Italian patients with adrenal lesions undergo surgery performed by surgeons with an annual case volume < 10 procedures, at centers with a low annual volume of adrenalectomies. Moreover, there is a lack of standardized definitions for 'expert surgeon' and 'high-volume center' in this context.

Adrenal incidentalomas, mostly adrenal adenomas, affect 3%-10% of the global population. Adrenocortical carcinoma (ACC) is rare, with an incidence of 0.7-2 cases per million. Adrenocortical oncocytic neoplasms (ACONs) account for about 10% of ACC cases, often discovered incidentally, with 17-34% being functionally active.We report a case of a woman in her 60s with treatment-resistant hypertension, diabetes and psychotic delirium. Imaging revealed a 6 cm left adrenal mass with marginally elevated metanephrines. Laparoscopic adrenalectomy was performed. Histology confirmed ACON. Positive margins necessitated adjuvant chemotherapy and radiotherapy. Postoperatively, psychiatric symptoms and hypertension resolved, indicating the tumour's secretory nature.This case highlights the diverse ACONs hormonal secretions, leading to complex clinical presentations, including metabolic and psychiatric symptoms. ACONs secretory nature may not be reflected in standard hormonal panels.ACONs challenging diagnosis and management emphasise the need for a multidisciplinary approach and further research.

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with a high risk of postoperative recurrence. Although adjuvant mitotane is commonly used, its potential for achieving cure rather than simply postponing inevitable recurrence remains uncertain. This study investigates whether mitotane impacts ACC recurrence patterns by preventing or delaying recurrence.

This retrospective analysis used data from the ICARO-GETTHI/SEEN registry, which includes 36 Spanish hospitals. Recurrence in non-metastatic ACC patients after resection was analyzed using Cox models, flexible longitudinal models, and mixture cure models to evaluate the impact of mitotane.

Among 244 patients, 133 (52%) received adjuvant mitotane, with therapeutic levels monitored in 84%. Findings suggest a possible "cure fraction" with a 32.5% estimated 30-year cure rate (95% CI, 23.4%-45.0%). Cox regression indicated a 39% reduced recurrence risk (HR 0.61; 95% CI, 0.39-0.95) for mitotane-treated patients, with effects diminishing over 24 months. Mixture cure models suggest mitotane primarily delays rather than prevents recurrence. Effect modification analysis showed significant benefit in males (HR 0.33; 95% CI, 0.16-0.69), younger patients, tumors with higher Ki-67% (modeled as a continuous variable), and those with venous invasion (HR 0.47; 95% CI, 0.27-0.82), with potential synergy when combined with radiotherapy.

This study underscores the intriguing possibility that adjuvant mitotane delays recurrence, yet questions remain as to its curative capacity. The early benefit suggests a cytostatic effect, but certain subgroups-especially males, younger individuals, and those with high-risk tumors-may experience a more durable outcome. Further research is needed to explore mitotane's curative potential in ACC management.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited treatment options. Although there have been recent advancements revealing genomic drivers of these tumors, it remains unclear which genomic signatures are associated with recurrence, particularly following R0 resection.

Adrenocortical carcinoma patients treated with adrenalectomy in the Cancer Genome Atlas with recurrence data were identified using cBioPortal. Clinicopathologic variables, genomics, treatment patterns, and outcomes were retrospectively analyzed.

Among 92 adrenocortical carcinoma patients, 84 had recurrence data, with 52% experiencing tumor recurrence. Age and sex were not significantly different between recurrent and nonrecurrent groups. Nonrecurrent patients had a significantly longer overall survival (54 months vs 35 months, P = .0036). Adjuvant radiation was administered similarly in both groups (25.0% vs 16.2%, P = .4164). There were no differences in capsular or venous invasion or median tumor size. Sixty-two patients had R0 resection and 40.3% (n = 25/62) recurred. Multivariate logistic regression in this cohort, when controlling for vascular invasion, venous invasion, and capsular invasion, revealed that the WNT (odds ratio 4.43 [1.09-18.0], P = .034), PI3K (odds ratio 7.80 [1.33-45.65], P = .023), and cell cycle (odds ratio 6.81 [1.43-32.30], P = .016) pathways were significantly associated with recurrence. Median time to recurrence was 7.9 months; early recurrence (<7.9 months) was associated with MYC pathway alterations (40.9% vs 9.1%, P = .0339).

This study identified genomic signatures in the PI3K, WNT, and cell cycle pathways associated with adrenocortical carcinoma recurrence, including in those who underwent R0 resection. Investigations regarding the utility of these signatures as a prognostic tool to dictate adjuvant therapies or targeted treatment are warranted.

Delays in management of adrenocortical carcinoma (ACC) may lead to worse outcomes. We assessed for delays in ACC treatment according to sociodemographic factors.

We performed a retrospective cohort study of patients treated for ACC (2010-2019) utilizing the National Cancer Database. Cox proportional hazards modeling was used to evaluate the associations between sociodemographic, geographic, and clinical factors and time to intervention from diagnosis.

Across 1399 subjects treated for ACC, the median time to treatment was 27 days (IQR 15-47). Non-Hispanic Black patients (HR 0.798, p ​= ​0.033) and patients aged 40-64 years (HR 0.800, p ​= ​0.008) were at greater risk of delays in care, whereas female patients (HR 1.169, p ​= ​0.011) and those with metastatic disease (HR 1.176, p ​= ​0.010) received more timely care.

Older age, male sex, and Black race were associated with delays in care for ACC though these delays did not translate to worsened overall survival.

Lymph node dissection improves adrenocortical carcinoma staging, but remains anatomically poorly defined. This ambiguity stems from limited knowledge of the adrenals lymphatic network. This work aims to define lymph node dissection for adrenocortical carcinoma through a systematic review and anatomical study.

First, an anatomical study was conducted on fresh cadavers by injecting blue dye into each adrenal gland before dissection. Concurrently, a systematic review of anatomical and clinical studies was performed, focusing on adrenals lymphatic network, lymph node dissection, and location of invaded lymph nodes in surgical series.

Twelve adrenals from 6 cadavers were resected en bloc with a median of 3 lymph nodes (1.5-6) removed. Screening of 6,506 studies revealed (1) 18 anatomical studies on cadavers detailing a 3-stage compartmentalized adrenals lymphatic network with distinct right/left lymph nodes relays; (2) 4 clinical studies highlighting discrepancies in lymph node involvement in adrenocortical carcinoma patients compared with anatomical description of adrenals lymphatic network, notably: lower implication of celiac lymph node, preponderance of ipsilateral renal hilum lymph nodes, potential contralateral involvement; (3) 21 series of adrenocortical carcinoma surgery demonstrating the heterogeneity of lymph node dissection practice (22% ± 4% lymph node dissection rate), with an average of 2.7 ± 0.6 lymph nodes removed, already fewer than in our cadaveric study.

Synthesis of anatomical and clinical studies suggest the following lymph node dissection protocol during adrenocortical carcinoma resection: capsular, renal hilum, para-cava, and inter-aortic-cava lymph nodes (right adrenocortical carcinoma); and capsular, renal hilum, para-aortic, and inter-aortic-cava lymph nodes (left adrenocortical carcinoma).

Adrenocortical carcinomas are rare but aggressive tumors that are frequently discovered as incidentalomas. Secretory tumors often lead to endocrine abnormalities, namely cushingoid features, virilization, or feminization. Non-functioning tumors, on the other hand, can be completely dormant with an insidious course or cause malaise, weight loss, abdominal pain, etc. Biochemical testing must be pursued in all patients with incidentalomas to detect pheochromocytoma, excess cortisol, or aldosterone secretion. In this report, we describe the case of a 37-year-old man who was lost to follow-up for two years following diagnosis with adrenal incidentaloma. This led to delayed diagnosis of adrenal carcinoma and eventual mortality. Periodic surveillance of adrenal incidentalomas is therefore imperative for timely interception of malignant lesions.

The application of multidisciplinary techniques in the management of endocrine-related cancers is crucial for harnessing the advantages of multiple disciplines and their coordinated efforts in eliminating tumors. Due to the malignant characteristics of cancer cells, they possess the capacity to develop resistance to traditional treatments such as chemotherapy and radiotherapy. Nevertheless, despite diligent endeavors to enhance the prediction of outcomes, the overall survival rate for individuals afflicted with endocrine-related malignancy remains quite miserable. Hence, it is imperative to investigate innovative therapy strategies. The latest advancements in therapeutic tactics have offered novel approaches for the therapy of various endocrine tumors. This paper examines the advancements in nano-drug delivery techniques and the utilization of nanomaterials for precise cancer cures through targeted therapy. This review provides a thorough analysis of the potential of combined drug delivery strategies in the treatment of thyroid cancer, adrenal gland tumors, and pancreatic cancer. The objective of this study is to gain a deeper understanding of current therapeutic approaches, stimulate the development of new drug DDS, and improve the effectiveness of treatment for patients with these diseases. The intracellular uptake of pharmaceuticals into cancer cells can be significantly improved through the implantation of synthetic or natural substances into nanoparticles, resulting in a substantial reduction in the development of endocrine malignancies.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis and limited treatment options. Bulk genomic characterization of ACC has not yielded obvious therapeutic or immunotherapeutic targets, yet novel therapies are needed. We hypothesized that elucidating the intratumoral cellular heterogeneity by single nuclei RNA sequencing analyses would yield insights into potential therapeutic vulnerabilities of this disease. In addition to characterizing the immune cell and fibroblast landscape, our analyses of single nuclei gene expression profiles identified an adrenal cortex cell cluster exhibiting a program of replication stress and DNA damage response in primary and metastatic ACC. In vitro assessment of replication stress and DNA damage response using an ACC cell line and a series of newly-derived hormonally active patient-derived tumor organoids revealed ATR sensitivity. These findings provide novel mechanistic insight into ACC biology and suggest that an underlying dependency on ATR may be leveraged therapeutically in advanced ACC.

Image-guided therapies (IGTs) are commonly used in oncology, but their role in adrenocortical carcinoma (ACC) is not well defined.

A retrospective review of patients with ACC treated with IGTs. We assessed response to therapy using RECIST v1.1, time to next line of systemic therapy, disease control rate (DCR), local tumor progression-free survival (LTPFS), and complications of IGTs (based on the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0).

Our cohort included 26 patients (median age 56 years [range 38-76]; n = 18 female) who had 51 IGT sessions to treat 86 lesions. IGTs modalities included cryoablation (n = 49), microwave ablation (n = 21), combined microwave and bland trans-arterial embolization (n = 8), bland trans-arterial embolization alone (n = 3), radio-embolization (n = 3), and radiofrequency ablation (n = 2). DCR was 81.4% (70 out of 86), of which 66.3% of tumors showed complete response, 18.6% showed progressive disease, 8.1% showed partial response, and 7.0% showed stable disease. LTPFS rates were 73% and 63% at 1 and 2 years, respectively. Fourteen lesions underwent re-ablation for incomplete response on initial treatment. Sixteen patients (61.5%) received new systemic therapy following IGTs, with a median time to systemic therapy of 12.5 months (95% CI: 8.6 months upper limit not reached). There was 1 reported CTCAE grade 3 adverse event (biloma) following IGT.

IGT use in properly selected patients with ACC is safe and associated with prolonged disease control and delay in the need for systemic therapy.

Adrenocortical carcinoma is a very rare oncologic condition with poor prognosis that usually metastasizes to the lungs, liver, local lymph nodes, and peritoneum at initial presentation. However, skin metastasis is very uncommon and has rarely been reported even in advanced stages of the disease. We present a case of a 41-year-old man with a known history of adrenocortical carcinoma of the right adrenal gland that presented with an arm mass. The histopathologic sections showed a multinodular necrotic malignant neoplasm in dermis and subcutaneous fat composed of atypical epithelioid cells with ample granular cytoplasm and pleomorphic vesicular nuclei with frequent intranuclear inclusions and atypical mitoses. The immunohistochemical stains showed tumor cells that were strongly positive for synaptophysin and inhibin, only focally positive for Melan-A, and negative for AE1/AE3. The histopathologic features and the immunohistochemical profile confirmed the diagnosis of metastatic carcinoma consistent with adrenal cortical origin. The diagnosis can be difficult (especially when no clinical data are provided), and an immunohistochemical battery is often useful in distinguishing this tumor from other tumors with similar cytomorphological features.

Adrenocortical carcinoma (ACC) is a rare primary carcinoma originating in the adrenal gland with a poor prognosis and a high recurrence rate. This study evaluated the risk factors associated with recurrence in patients with early stage ACC after curative surgical resection.

The present study retrospectively evaluated the risk factors for recurrence in 38 patients with stages 1 and 2 ACC who underwent curative resection between 1995 and 2020.

Recurrence was observed in 21 patients (55.3%), with no significant difference between stages 1 and 2 ACC (P = 0.640). The overall recurrence rate was higher in patients who underwent minimally invasive surgery than open adrenalectomy (71.4% vs. 51.6%). Of the 33 patients with gross tumor margins negative for malignancy, 16 (48.5%) experienced tumor recurrence, and all 5 patients with positive and unknown gross resection margins had recurrence. Recurrences were observed in 14 of the 30 patients (46.7%) negative for pathologic resection margins, 6 of the 7 patients (85.7%) with pathologically indeterminate margins, and 1 patient with pathologically positive margins.

The recurrence rates are high even in patients with early stage ACC, being higher in patients who undergo minimally invasive surgery than open adrenalectomy. Obtaining clear resection margins during surgery may reduce tumor recurrence; however, gross or pathologic margin safety was not a secure factor in preventing recurrence. None of the factors analyzed was a definitive predictor of poor prognosis.

Adrenal tumors, such as adrenocortical carcinoma (ACC), adrenocortical adenoma (ACA), and pheochromocytoma (PCC) are complex diseases with unclear causes and treatments. Mitochondria and mitochondrial-derived peptides (MDPs) are crucial for cancer cell survival. The primary aim of this study was to analyze samples from different adrenal diseases, adrenocortical carcinoma, adrenocortical adenoma, and pheochromocytoma, and compare them with normal adrenal tissue to determine whether the expression levels of the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) gene and protein vary between different types of adrenal tumors compared to healthy controls using qPCR, ELISA, and IHC methods. Results showed decreased MOTS-c mRNA expression in all adrenal tumors compared to controls, while serum MOTS-c protein levels increased in ACA and PCC but not in ACC. The local distribution of MOTS-c protein in adrenal tissue was reduced in all tumors. Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex. Tumor size and testosterone levels positively correlated with MOTS-c mRNA but negatively with serum MOTS-c protein. Additionally, serum MOTS-c protein correlated positively with glucose, total cholesterol, HDL, LDL, and SHGB levels. These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue associated with disease progression. This study provides a detailed examination of MOTS-c mRNA and protein in adrenal tumors, indicating the potential role of MDPs in tumor biology and progression.

Adrenal cortical carcinoma (ACC) is a rare malignancy with a generally poor but heterogeneous prognosis, especially depending on the tumour stage at diagnosis. Identification of somatic gene alterations combined with clinical/histopathological evaluation of the tumour can help improve prognostication. We applied a simplified targeted-Next-Generation Sequencing (NGS) panel to characterise the mutational profiles of ACCs, providing potentially relevant information for better patient management.

Thirty frozen tumour specimens from a local ACC series were retrospectively analysed by a custom-NGS panel (CDKN2A, CTNNB1, DAXX, MED12, NF1, PRKAR1A, RB1, TERT, TP53, ZNRF3) to detect somatic prioritised single-nucleotide variants. This cohort was integrated with 86 patients from the ACC-TCGA series bearing point-mutations in the same genes and their combinations identified by our panel. Primary endpoints of the analysis on the total cohort (113 patients) were overall survival (OS) and progression-free survival (PFS), and hazard ratio (HR) for the different alterations grouped by the signalling pathways/combinations affected.

Different PFS, OS, and HR were associated to the different pathways/combinations, being NF1 + TP53 and Wnt/β-catenin + Rb/p53 combined mutations the most deleterious, with a statistical significance for progression HR which is retained only in low-(I/II) stages-NF1 + TP53 combination: HR = 2.96[1.01-8.69] and HR = 13.23[3.15-55.61], all and low stages, respectively; Wnt/β-catenin + Rb/p53 combined pathways: HR = 6.47[2.54-16.49] and HR = 16.24[3.87-68.00], all and low-stages, respectively.

A simplified targeted-NGS approach seems the best routinely applicable first step towards somatic genetic characterisation of ACC for prognostic assessment. This approach proved to be particularly promising in low-stage cases, suggesting the need for more stringent surveillance and personalised treatment.

Adrenocortical carcinoma (ACC) is one of the most lethal endocrine malignancies and there is a lack of clinically useful markers for prognosis and patient stratification. Therefore our aim was to identify clinical and genetic markers that predict outcome in patients with ACC.

Clinical and genetic data from a total of 162 patients with ACC were analyzed by combining an independent cohort consisting of tumors from Yale School of Medicine, Karolinska Institutet, and Düsseldorf University (YKD) with two public databases [The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)]. We used a novel bioinformatical pipeline combining differential expression and messenger RNA (mRNA)- and DNA-dependent survival. Data included reanalysis of previously conducted whole-exome sequencing (WES) for the YKD cohort, WES and RNA data for the TCGA cohort, and RNA data for the GEO cohort.

We identified 3903 significant differentially expressed genes when comparing ACC and adrenocortical adenoma, and the mRNA expression levels of 461/3903 genes significantly impacted survival. Subsequent analysis revealed 45 of these genes to be mutated in patients with significantly worse survival. The relationship was significant even after adjusting for stage and age. Protein-protein interaction showed previously unexplored interactions among many of the 45 proteins, including the cancer-related proteins DNA polymerase delta 1 (POLD1), aurora kinase A (AURKA), and kinesin family member 23 (KIF23). Furthermore 14 of the proteins had significant interactions with TP53 which is the most frequently mutated gene in the germline of patients with ACC.

Using a multiparameter approach, we identified 45 genes that significantly influenced survival. Notably, many of these genes have protein interactions not previously implicated in ACC. These findings may lay the foundation for improved prognostication and future targeted therapies.

The prognostic significance of tumor size with adrenocortical carcinoma (ACC) patients has not yet been thoroughly evaluated. Our objective was to investigate the influence of tumor size on prognostic value in adult ACC patients.

The Surveillance, Epidemiology and End Results Program (SEER) was employed to identify adult ACC patients who had been diagnosed from 2004 to 2015. The "X-Tile" program determined the optimal cutoff value of tumor size. Cancer-specific survival (CSS) and overall survive (OS) were estimated. The survival outcomes and risk factors were analyzed by the Kaplan-Meier methods and the multivariable cox regression respectively.

A total 426 adult ACC patients were included. Univariable and multivariable cox analysis revealed age, larger tumor size and metastasis as consistent predictors of lower CSS and OS. The optimal cutoff value of tumor size was identified as 8.5 cm using X-tile software, and Kaplan-Meier method showed dramatic prognostic difference between patients with larger tumors (＞8.5 cm) and smaller tumors (≤8.5 cm) (log-rank test, P < 0.001). Subgroup analyses revealed no statistical significance and a consistent proportionate effect of tumor size on CSS and OS across all eight pre-specified subgroups. Interestingly, an additional subgroup analysis showed that ACC patients could not benefit from chemotherapy in terms of CSS and OS.

The study suggests that tumor size is a crucial prognostic factor in ACC patients and a cutoff value 8.5 cm might indicate a poor outcome. Given the limitations of the available data, it is challenging to conclusively determine the benefit of chemotherapy in adult ACC patients across different tumor size ranges.

Adrenocortical carcinoma (ACC) patients with glucocorticoid excess have been reported to be associated with decreased tumor-infiltrating immune cells, but the effects of in situ glucocorticoid production on tumor immunity have remained unknown. In addition, ACC was also known to harbor marked intra-tumoral heterogeneity of steroidogenesis or disorganized steroidogenesis. Therefore, in this study, we immune-profiled tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) and pivotal steroidogenic enzymes of glucocorticoid biosynthesis (CYP17A and CYP11B1) to explore the potential effects of in situ glucocorticoid production and intra-tumoral heterogeneity/disorganized steroidogenesis on tumor immunity of ACC. We also studied the correlations of the status of tumor immunity with that of angiogenesis and tumor grade to further explore the tumor tissue microenvironment of ACC. TILs (CD3, CD4, CD8, and FOXP3), TAMs (CD68 and CD163), key steroidogenic enzymes of glucocorticoid (CYP17A and CYP11B1), angiogenesis (CD31 and vasohibin-1 (VASH-1)), tumor grade (Ki-67 and Weiss score) were immunohistochemically evaluated in 34 ACCs. Increased CYP17A immunoreactivity in the whole tumor area was significantly positively correlated with FOXP3-positive TILs (p = 0.021) and negatively with CD4/CD3 ratio (p = 0.001). Increased CYP11B1 immunoreactivity in the whole tumor area was significantly positively correlated with CD8/CD3 (p = 0.039) and CD163/CD68 ratios (p = 0.006) and negatively with CD4-positive TILs (p = 0.036) and CD4/CD3 ratio (p = 0.001). There were also significant positive correlations between CYP17A and CD8 (r = 0.334, p < 0.001) and FOXP3-positive TILs (r = 0.414, p < 0.001), CD8/CD3 ratio (r = 0.421, p < 0.001), and CD68-positive TAMs (r = 0.298, p < 0.001) in randomly selected areas. Significant positive correlations were also detected between CYP11B1 and CD8/CD3 ratio (r = 0.276, p = 0.001) and negative ones detected between CYP11B1 and CD3- (r = -0.259, p = 0.002) and CD4-positive TILs (r = -0.312, p < 0.001) in those areas above. Increased micro-vessel density (MVD) -VASH-1 was significantly positively correlated with CD68- (p = 0.015) and CD163-positive TAMs (p = 0.009) and CD163/CD68 ratio and the high VASH-1 with CD163-positive TAMs (p = 0.042). Ki-67 labeling index was significantly positively correlated with MAD-VASH-1 (p = 0.006) and VASH-1 (p = 0.006) status. Results of our present study indicated that in situ glucocorticoid production did influence the status of tumor immunity in ACC. In particular, increased levels of CYP17A and CYP11B1, both involved in glucocorticoid producing immunoreactivity played different effects on tumor immunity, i.e., reflecting the involvement of intra-tumoral heterogeneity and disorganized steroidogenesis of ACC, which also did indicate the importance of in situ approaches when analyzing tumor immunity of ACC.

Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis.

A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses.

The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses.

ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

Adrenocortical carcinoma has a poor prognosis and multiple clinical, pathological, and treatment variables. Currently, we lack a prognostic and treatment calculator to determine the survival and efficacy of adjuvant chemoradiation. We aimed to validate a calculator to assess prognosis and treatment.

We searched the National Cancer Database to identify patients with adrenocortical carcinoma surgically treated from 2004 to 2020 and randomly allocated them into a training (80%) or validation set (20%). We analyzed the variables of age; sex; Charlson Comorbidity Index; insurance status; tumor size; pathologic tumor, node, and metastasis categories; surgical margins; and use of chemotherapy and radiation therapy. We used Cox regression prediction models and bootstrap coefficients to generate a mathematical model to predict 5- and 10-year overall survival. After using the area under the curve analysis to assess the model's performance, we compared overall survival in the training and validation sets.

Multivariable analysis of the 3,480 patients included in the study revealed that all variables were significant except sex (P < .05) and incorporated into a mathematical model. The area under the curve for 5- and 10-year overall survival was 0.68 and 0.70, respectively, for the training set and 0.70 and 0.72, respectively, for the validation set. For the bootstrap coefficients, the 5- and 10-year overall survival was 6.4% and 4.1%, respectively, above the observed mean.

Our model predicts the overall survival of patients with adrenocortical carcinoma based on clinical, pathologic, and treatment variables and can assist in individualizing treatment.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis due to high postoperative recurrence rates. The aim of this study is to develop a contrast CT radiomic feature-based prognosis prediction model for ACC and evaluate its performance by comparison with ENSAT staging system and S-GRAS score.

Included in this study were 39 ACC patients, from which we extracted 1411 radiomic features. Using cross-validated least absolute shrinkage and selection operator regression (cv-LASSO regression), we generated a radiomic index. Additionally, we further validated the radiomic index using both univariate and multivariate Cox regression analyses. We constructed a radiomic nomogram that incorporated the radiomic signature and compared it with ENSAT stage and S-GRAS score in terms of calibration, discrimination and clinical usefulnes.

In this study, the average progression free survival (PFS) of 39 patients was 20.4 (IQR 9.1-60.1) months and the average overall survival (OS) was 57.8 (IQR 32.4-NA). The generated radiomic features were significantly associated with PFS, OS, independent of clinical-pathologic risk factors (HR 0.16, 95%CI 0.02-0.99, p = 0.05; HR 0.20, 95%CI 0.04-1.07, p = 0.06, respectively). The radiomic index, ENSAT stage, resection status, and Ki67% index incorporated nomogram exhibited better performance for both PFS and OS prediction as compared with the S-GRAS and ENSAT nomogram (C-index: 0.75 vs. C-index: 0.68, p = 0.030 and 0.67, p = 0.025; C-index: 0.78 vs. C-index: 0.72, p = 0.003 and 0.73, p = 0.006). Calibration curve analysis showed that the radiomics-based model performs best in predicting the two-year PFS and the three-year OS. Decision curve analysis demonstrated that the radiomic index nomogram outperformed the S-GRAS and ENSAT nomogram in predicting the two-year PFS and the three-year OS.

The contrast CT radiomic-based nomogram performed better than S-GRAS or ENSAT in predicting PFS and OS in ACC patients.

Over recent years, there has been increasing adoption of minimally invasive surgery (MIS) in the treatment of adrenocortical carcinoma (ACC). However, MIS has been associated with noncurative resection and locoregional recurrence. We aimed to identify risk factors for margin-positivity among patients who undergo MIS resection for ACC. We hypothesized that a simple nomogram can accurately identify patients most suitable for curative MIS resection.

Curative-intent resections for ACC were identified through the National Cancer Database spanning 2010-2018. Trends in MIS utilization were reported using Pearson correlation coefficients. Factors associated with margin-positive resection were identified among preoperatively available variables using multivariable logistic regression, then incorporated into a predictive model. Model quality was cross validated using an 80% training data set and 20% test data set.

Among 1260 ACC cases, 38.6% (486) underwent MIS resection. MIS utilization increased over time at nonacademic centers (R = 0.818, p = 0.007), but not at academic centers (R = 0.009, p = 0.982). Factors associated with margin-positive MIS resection were increasing age, nonacademic center (odds ratio [OR]: 1.8, p = 0.006), cT3 (OR: 4.7, p < 0.001) or cT4 tumors (OR: 14.6, p < 0.001), and right-sided tumors (OR: 2.0, p = 0.006). A predictive model incorporating these four factors produced favorable c-statistics of 0.75 in the training data set and 0.72 in the test data set. A pragmatic nomogram was created to enable bedside risk stratification.

An increasing proportion of ACC are resected via minimally invasive operations, particularly at nonacademic centers. Patient selection based on a few key factors can minimize the risk of noncurative surgery.

The objective was to retrospectively evaluate the contribution of fluorodeoxyglucose [18F] positron emission tomography/computed tomography (18FDG-PET/CT) to the re-staging of adrenocortical carcinoma (ACC).

A total of 16 patients (10 males and 6 females), who underwent adrenalectomy due to adrenocortical carcinoma and 18FDG-PET/CT scan to re-stage the tumor between July 2007 and April 2013, were included in the present study. The mean age was 53.37 ± 13.91 years (min: 30, max: 74) The patients were required to fast for six hours prior to scanning, and whole-body PET scanning from the skull base to the upper thighs was performed approximately 1 h after the intravenous injection of 555 MBq of F-18 FDG. Whole body CT scanning was performed in the cranio-caudal direction. FDG-PET images were reconstructed using CT data for attenuation correction. Suspicious recurrent or metastatic lesions were confirmed by histopathology or clinical follow-up.

Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18FDG-PET/CT were 100%, 83.3%, 90.9%, 83.3%, and 93.7%, respectively.

18FDG-PET/CT detects local recurrence and/or distant metastases with high accuracy in the re-staging of operated adrenocortical carcinoma. It is considered that the procedure could play an important role in treatment decision after the operation and post-operative follow-up and could influence the entire decision-making process.

Adrenocortical carcinoma (ACC) is an aggressive, deadly malignancy. Resection remains the primary treatment; however, there is conflicting evidence regarding the optimal approach to and extent of surgery and the role of adjuvant therapy. We evaluated the impact of surgical technique and adjuvant therapies on survival in non-metastatic ACC.

We performed a retrospective cohort study of subjects who underwent surgery for non-metastatic ACC between 2010 and 2019 utilizing the National Cancer Database. The primary outcome was overall survival. Cox proportional hazards models were developed to identify associations between clinical and treatment characteristics and survival.

Overall, 1175 subjects were included. Their mean age was 54 ± 15 years, and 62% of patients were female. 67% of procedures were performed via the open approach, 22% involved multi-organ resection, and 26% included lymphadenectomy. Median survival was 77.1 months. Age (hazard ratio [HR] 1.019; p < 0.001), advanced stage (stage III HR 2.421; p < 0.001), laparoscopic approach (HR 1.329; p = 0.010), and positive margins (HR 1.587; p < 0.001) were negatively associated with survival, while extent of resection (HR 1.189; p = 0.140) and lymphadenectomy (HR 1.039; p = 0.759) had no association. Stratified by stage, laparoscopic resection was only associated with worse survival in stage III disease (HR 1.548; p = 0.007). Chemoradiation was only associated with improved survival in patients with positive resection margins (HR 0.475; p = 0.004).

Tumor biology and surgical margins are the primary determinants of survival in non-metastatic ACC. Surgical extent and lymphadenectomy are not associated with overall survival. In advanced disease, the open approach is associated with improved survival.

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.

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.

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).

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.

Adrenocortical carcinoma (ACC) is a rare malignant tumor originating in the adrenal cortex and characterized by poor 5-year survival. It occurs with a frequency of 2-4 cases per 2 million in the population. Women are more frequently affected than men and it is mostly detected in the fourth and fifth decades. In the most of cases, the cancerogenesis occurs sporadically because of gene driver mutations in somatic adrenocortical cells, in other cases it can be found as part of a genetically determined syndrome such as Li-Fraumeni syndrome or Wermer's syndrome (multiple endocrine adenomatosis type I). ACC most frequently happens occurs without symptoms in the initial stages leading to poor diagnoses. Because of this lack of early detection, the tumor is not considered malignant reducing the benefits of further treatment. Sometimes the fact that the resected tumor is indeed adrenocortical carcinoma becomes clear only after recurrence, or after the appearance of metastases. We present a case of adrenocortical carcinoma in a 46-year-old woman who went to the doctor in 1.5 year after symptoms were manfested. This clinical case illustrates the consequences of late diagnosis of a malignant tumor. We would like to emphasize the importance of timely detection of a neoplasm, using all of the potential of laboratory-instrumental and genomic analysis. Due to low oncological awareness, our patient was slow to seek medical help, which in turn led not only to metastases, but also to complications in the cardiovascular system.

Adrenocortical carcinoma (ACC) represents a rare tumor entity with limited treatment options and usually rapid tumor progression in case of metastatic disease. As further treatment options are needed and ACC metastases are sensitive to external beam radiation, novel theranostic approaches could complement established therapeutic concepts. Recent developments focus on targeting adrenal cortex-specific enzymes like the theranostic twin [123/131I]IMAZA that shows a good image quality and a promising therapeutic effect in selected patients. But other established molecular targets in nuclear medicine such as the C-X-C motif chemokine receptor 4 (CXCR4) could possibly enhance the therapeutic regimen as well in a subgroup of patients. The aims of this review are to give an overview of innovative radiopharmaceuticals for the treatment of ACC and to present the different molecular targets, as well as to show future perspectives for further developments since a radiopharmaceutical with a broad application range is still warranted.

Radical surgery is a common treatment for patients with gastric cancer; however, it can lead to postoperative complications and intestinal barrier dysfunction. Ultrasound-guided quadratus lumborum block is often used for postoperative analgesia, but its effects on stress response and intestinal barrier function are not well understood.

To investigate the effects of an ultrasound-guided quadratus lumborum block on stress response and intestinal barrier function in patients undergoing radical surgery for gastric cancer.

A total of 100 patients undergoing radical surgery for gastric cancer were randomly categorized into observation and control groups. Plasma adrenaline and cortisol levels, intestinal mucosal barrier indexes, and complication rates were compared between the two groups before, during, and 1 day after surgery.

The observation group had significantly lower plasma adrenaline and cortisol levels during surgery and at 1 day postoperatively than that of the control group (P < 0.05). Additionally, intestinal barrier indexes (endotoxin and D-dimer) at 1 day postoperatively were significantly lower in the observation group than in the control group (P < 0.05).

Ultrasound-guided quadratus lumborum block could reduce stress response, protect intestinal barrier function, and decrease the incidence of complications in patients undergoing radical surgery for gastric cancer. This technique has the potential for clinical applications.

Adrenocortical carcinoma is a rare malignancy with an annual worldwide incidence of 1-2 cases per 1 million and a 5-year survival rate of <60%. Although adrenocortical carcinoma is rare, such rare cancers account for approximately one third of patients diagnosed with cancer annually. In the past decade, there have been considerable advances in understanding the molecular basis of adrenocortical carcinoma. The genetic events associated with adrenocortical carcinoma in adults are distinct from those of paediatric cases, which are often associated with germline or somatic TP53 mutations and have a better prognosis. In adult primary adrenocortical carcinoma, the main somatic genetic alterations occur in genes that encode proteins involved in the WNT-β-catenin pathway, cell cycle and p53 apoptosis pathway, chromatin remodelling and telomere maintenance pathway, cAMP-protein kinase A (PKA) pathway or DNA transcription and RNA translation pathways. Recently, integrated molecular studies of adrenocortical carcinomas, which have characterized somatic mutations and the methylome as well as gene and microRNA expression profiles, have led to a molecular classification of these tumours that can predict prognosis and have helped to identify new therapeutic targets. In this Review, we summarize these recent translational research advances in adrenocortical carcinoma, which it is hoped could lead to improved patient diagnosis, treatment and outcome.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis. The disease originates from the cortex of adrenal gland and lacks effective treatment. Efforts have been made to elucidate the pathogenesis of ACC, but the molecular mechanisms remain elusive. To identify key genes and pathways in ACC, the expression profiles of GSE12368, GSE90713 and GSE143383 were downloaded from the Gene Expression Omnibus (GEO) database. After screening differentially expressed genes (DEGs) in each microarray dataset on the basis of cut-off, we identified 206 DEGs, consisting of 72 up-regulated and 134 down-regulated genes in three datasets. Function enrichment analyses of DEGs were performed by DAVID online database and the results revealed that the DEGs were mainly enriched in cell cycle, cell cycle process, mitotic cell cycle, response to oxygen-containing compound, progesterone-mediated oocyte maturation, p53 signaling pathway. The STRING database was used to construct the protein-protein interaction (PPI) network, and modules analysis was performed using Cytoscape. Finally, we filtered out eight hub genes, including CDK1, CCNA2, CCNB1, TOP2A, MAD2L1, BIRC5, BUB1 and AURKA. Biological process analysis showed that these hub genes were significantly enriched in nuclear division, mitosis, M phase of mitotic cell cycle and cell cycle process. Violin plot, Kaplan-Meier curve and stage plot of these hub genes confirmed the reliability of the results. In conclusion, the results in this study provided reliable key genes and pathways for ACC, which will be useful for ACC mechanisms, diagnosis and candidate targeted treatment.

Regionalization of care is associated with improved perioperative outcomes after adrenalectomy. However, the relationship between travel distance and treatment of adrenocortical carcinoma (ACC) is unknown. We investigated the association between travel distance, treatment, and overall survival (OS) among patients with ACC.

Patients diagnosed with ACC between 2004 and 2017 were identified with the National Cancer Database. Long distance was defined as the highest quintile of travel (≥42.2 miles). The likelihood of surgical management and adjuvant chemotherapy (AC) were determined. The association between travel distance, treatment, and OS was evaluated.

Of 3492 patients with ACC included, 2337 (66.9%) received surgery. Rural residents were more likely to travel long distances for surgery than metropolitan residents (65.8% vs. 15.5%, p < 0.001), and surgery was associated with improved OS (HR 0.43, 95% CI 0.34-0.54). Overall, 807 (23.1%) patients received AC with rates decreasing approximately 1% per 4-mile travel distance increase. Also, long distance travel was associated with worse OS among surgically treated patients (HR 1.21, 95% CI 1.05-1.40).

Surgery was associated with improved overall survival for patients with ACC. However, increased travel distance was associated with lower likelihood to receive adjuvant chemotherapy and decreased overall survival.

Adrenalectomy is the treatment of choice in case of functional adrenal tumors and malignant adrenal incidentalomas. Laparoscopic adrenalectomy (LA) in dogs has gained popularity in recent years, however, clinical studies on large patient populations are scarce. This retrospective study describes perioperative and recurrence data, survival, and prognostic factors in 70 dogs that underwent LA or open adrenalectomy (OA) in our hospital between 2008 and 2022. Diagnosis was based on history, clinical signs, endocrine function tests and advanced diagnostic imaging. Laparoscopic adrenalectomy was performed in 42 dogs (n = 27 naturally occurring hypercortisolism, n = 4 pheochromocytoma, n = 1 pheochromocytoma with concurrent hypercortisolism, n = 10 incidentaloma) and OA in 28 dogs (n = 22 hypercortisolism, n = 3 pheochromocytoma, n = 3 incidentaloma). Bilateral adrenalectomy was performed in 8/70 dogs. Surgical duration of LA and OA did not differ significantly in unilateral and bilateral procedures (P = 0.108 and P = 0.101, respectively). Systemic hypertension occurred in 7/41 and 1/28 dogs during LA and OA, respectively (P = 0.130). Hypotension occurred in 2/41 and 4/28 dogs during LA and OA, respectively (P = 0.214). A total of 40/42 dogs in the LA group and 27/28 in the OA group survived to discharge (P = 0.810). Mean hospital stay was significantly shorter (P = 0.006) after LA (1.5 days, range 1-3) than after OA (2.2 days, range 1-4). No significant differences were demonstrated between LA and OA groups in recurrence of adrenal-dependent endocrine disease (P = 0.332), disease-free period (P = 0.733) and survival time (P = 0.353). The disease-specific 1-, 2- and 3-year survival rates were 95, 89, and 89% after LA and 92, 88, and 81% after OA. Tumor size was significantly associated with the occurrence of a recurrence. In addition, tumor size had a negative effect on the disease-free period and survival time. This study shows a favorable outcome of both LA and OA in dogs. Based on low perioperative complication rate, short hospitalization time and long-term outcomes comparable to OA in selected cases, the less invasive laparoscopic approach is considered the preferred technique.

Surgical resection of adrenocortical carcinoma (ACC) is the only curative treatment. Even in localized (I-II) stages, open adrenalectomy (OA) is the gold standard, though laparoscopic adrenalectomy (LA) can be proposed in selected patients. Despite the postoperative benefits of LA, its role in the surgical management of patients with ACC remains controversial regarding oncologic outcomes. The aim of this retrospective study was to compare the outcomes of patients with localized ACC submitted to LA or OA in a referral center from 1995 to 2020. Among 180 consecutive patients operated on for ACC, 49 presented with localized ACC (19 LA and 30 OA). Baseline characteristics were similar between groups, except for tumor size. Kaplan-Meier estimates of 5-year overall survival were similar in both groups (p = 0.166) but 3-year disease-free survival was in favor of OA (p = 0.020). Though LA could be proposed in highly selected patients, OA should still be considered the standard approach in patients with known or suspected localized ACC.