Cutaneous, Subcutaneous, and Bilateral Adrenal Gland Metastases in Progressive Prostate Carcinoma: Theranostic Potential of 68 Ga-PSMA-11 PET/CT Imaging and 177 Lu-PSMA-617 Therapy.

ABSTRACT: Prostate carcinoma (PC) is the second most common malignant tumor in males globally. The metastatic spread of PC usually involves the pelvic and abdominal lymph nodes and the skeletal system. Cutaneous metastases are exceedingly uncommon and typically manifest themselves late in the disease course, considered as ominous sign with limited treatment options and a poor prognosis. We describe a patient wherein 68 Ga-PSMA-11 PET/CT detected multiple uncommon metastatic sites in the cutaneous region of the scrotum, penis, and thigh, as well as in the subcutaneous region of anterior abdominal wall, and in bilateral adrenal glands. These findings served as a theranostic tool for selecting 177 Lu-PSMA-617 treatment for these extremely rare metastatic sites.

A novel method of tunneling retroperitoneoscopic adrenalectomy: a prospective study.

BACKGROUND: To introduce the surgical technique and our team's extensive experience with tunnel method in laparoscopic adrenalectomy. METHODS: From July 2019 to June 2022, we independently designed and conducted 83 cases of " Tunnel Method Laparoscopic Adrenalectomy," a prospective study. There were 45 male and 38 female patients, ages ranged from 25 to 73 years(mean: 44.6 years).The cases included 59 adrenal cortical adenomas, 9 pheochromocytomas, 6 cysts, 4 myelolipomas, 1 ganglioneuroma, and 4 cases of adrenal cortical hyperplasia. In terms of anatomical location, there were 39 cases on the left side, 42 on the right side, and 2 bilateral cases. Tumor diameters ranged from 0.6 to 5.9 cm(mean: 2.9 cm). Utilizing ultrasound monitoring, percutaneous puncture was made either directly to the target organ or its vicinity, and the puncture path was manually marked. Then, under the direct view of a single-port single-channel laparoscope, the path to the target organ in the retroperitoneum or its vicinity was further delineated and separated. This approach allowed for the insertion of the laparoscope and surgical instruments through the affected adrenal gland, thereby separating the surface of the target organ to create sufficient operational space for the adrenalectomy. RESULTS: All 83 surgeries were successfully completed. A breakdown of the surgical approach reveals that 51 surgeries were done using one puncture hole, 25 with two puncture holes, and 7 with three puncture holes. The operation time ranged from 31 to 105 min (mean: 47 min), with a blood loss of 10 to 220mL (mean: 40 mL). Notably, there were no conversions to open surgery and no intraoperative complications. Postoperative follow-up ranged from 6 to 28 months, during which after re-examination using ultrasound, CT, and other imaging methods, there were no recurrences or other complications detected. CONCLUSIONS: The completion of the tunnel method laparoscopic adrenalectomy represents a breakthrough, transitioning from the traditional step-by-step separation of retroperitoneal tissues to reach the target organ in conventional retroperitoneoscopic surgery. This method directly accesses the target organ, substantially reducing the damage and complications associated with tissue separation in retroperitoneoscopic surgery, As a result, it provides a new option for minimally invasive surgery of retroperitoneal organs and introduces innovative concepts to retroperitoneoscopic surgery.

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.

Cannabinoid hyperemesis and pheochromocytoma hypertensive urgency: a case report.

BACKGROUND: This report presents a case of cannabinoid-induced hyperemesis syndrome causing repeated violent retching in a patient with a large (8 cm) adrenal pheochromocytoma resulting in hypertensive urgency. CASE PRESENTATION: A 69-year-old white male patient with a previously diagnosed pheochromocytoma presented to the emergency department with nausea and vomiting and was found to have hypertensive urgency. Computed tomography scan did not show any acute abdominal pathology and history was inconsistent with a gastrointestinal etiology. Patient had a history of daily cannabinoid use for many years and repeated self-limited hyperemesis episodes, and thus a diagnosis of cannabinoid-induced hyperemesis syndrome was made. It was concluded that the likely explanation for the hypertensive urgency was from physical compression of his adrenal tumor during the episodes of retching resulting in a catecholamine surge. The patient was given antiemetics and admitted to the intensive care unit for blood pressure management. Blood pressure was initially controlled with phentolamine and a clevidipine infusion, then transitioned to oral doxazosin and phenoxybenzamine. Hyperemesis and abdominal pain resolved after 24 hours, and his blood pressure returned to baseline. The patient was discharged with the recommendation to stop all cannabis use. On follow-up, his blood pressure remained well controlled, and he subsequently underwent adrenalectomy for tumor removal. CONCLUSION: Hyperemesis can cause hypertensive events in patients with pheochromocytoma by increasing abdominal pressure, leading to catecholamine release.

Imaging of Pheochromocytomas and Paragangliomas.

Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations translate into different clusters with distinct tumor locations, biochemical/metabolomic features, tumor cell characteristics (eg, receptors, transporters), and disease course. Such tumor heterogeneity calls for different imaging strategies in order to provide proper diagnosis and follow-up. This also warrants selection of the most appropriate and locally available imaging modalities tailored to an individual patient based on consideration of many relevant factors including age, (anticipated) tumor location(s), size, and multifocality, underlying genotype, biochemical phenotype, chance of metastases, as well as the patient's personal preference and treatment goals. Anatomical imaging using computed tomography and magnetic resonance imaging and functional imaging using positron emission tomography and single photon emission computed tomography are currently a cornerstone in the evaluation of patients with pheochromocytomas/paragangliomas. In modern nuclear medicine practice, a multitude of radionuclides with relevance to diagnostic work-up and treatment planning (theranostics) is available, including radiolabeled metaiodobenzylguanidine, fluorodeoxyglucose, fluorodihydroxyphenylalanine, and somatostatin analogues. This review amalgamates up-to-date imaging guidelines, expert opinions, and recent discoveries. Based on the rich toolbox for anatomical and functional imaging that is currently available, we aim to define a customized approach in patients with (suspected) pheochromocytomas/paragangliomas from a practical clinical perspective. We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.

To report hounsfeld units or not: There is no question.

INTRODUCTION: Most adrenal incidentalomas are not appropriately evaluated. Reporting the mass in the radiology report summary and providing recommendations in the report can positively impact evaluation. This study evaluated the effect of reporting Hounsfield units(HU) on adrenal incidentaloma follow-up. METHODS: Patients with adrenal incidentalomas identified on noncontrast CT scan from 2015 to 2020 â€‹at a tertiary care institution were studied. Chart review was conducted. Patient and imaging characteristics were compared between patients who did and did not have HU reported. Outcomes of interest were 1)outpatient referral, 2)biochemical evaluation, and 3)dedicated imaging if appropriate. Multivariate analysis determined the impact of HU, reporting in the summary and provision of recommendations on the outcomes. RESULTS: 363 patients were studied, 36(9.9 â€‹%) had HU reported. When HU were used in addition to recommendations and reporting in the summary, the likelihood of outpatient referral increased from 10.1 to 32.6-fold (95%CI 7.7-138.1, p â€‹< â€‹0.001). Similarly, the likelihood of biochemical workup increased from 2.5 to 7.8-fold (95%CI 2.5-24.1, p â€‹< â€‹0.001). CONCLUSION: Recording adrenal incidentaloma HU on non-contrast CT scans was associated with increased rates of outpatient referral and biochemical workup.

Perirenal fat thickness is a powerful predictor for surgical outcomes of transperitoneal laparoscopic adrenalectomy.

OBJECTIVES: Laparoscopic adrenalectomy has been the gold standard surgical procedure. However, the adaptation criteria for malignant tumors and predictors of perioperative outcomes are not well defined. Therefore, this study tried to identify valid predictors for perioperative outcomes of laparoscopic adrenalectomy and consider the adaptation criteria. METHODS: We retrospectively reviewed the preoperative and perioperative data of 216 patients who underwent transperitoneal laparoscopic adrenalectomy in our hospital. Preoperative factors associated with perioperative outcomes were analyzed using multiple regression analysis. RESULTS: Among 216 patients, 165 (76.4%), 26 (12.0%), and 25 (11.6%) were suspected of having benign tumors, pheochromocytoma, and malignant tumors, respectively. Median tumor size was 25.0 mm (interquartile range 18.0-35.0); median perirenal fat thickness was 9.2 mm (interquartile range 4.9-15.6) on preoperative computed tomography scans. The median operative time was 145.5 min (interquartile range 117.5-184.0) and the median estimated blood loss was 0.0 mL (interquartile range 0.0-27.3). Perirenal fat thickness (p < 0.001), tumor size (p < 0.001), and malignant tumors (p = 0.020) were associated with operative time, and perirenal fat thickness (p = 0.038) and malignant tumors (p = 0.002) were associated with estimated blood loss. CONCLUSIONS: Perirenal fat thickness, tumor size, and malignant tumors are valid predictors of the surgical outcomes of transperitoneal laparoscopic adrenalectomy. As only perirenal fat thickness is associated with both surgical outcomes except for malignant tumors, it is a powerful predictor. Transperitoneal laparoscopic adrenalectomy for large malignant adrenal tumors with thick perirenal fat should be performed with caution.

Ensemble Machine Learning Model Incorporating Radiomics and Body Composition for Predicting Intraoperative HDI in PPGL.

CONTEXT: Intraoperative hemodynamic instability (HDI) can lead to cardiovascular and cerebrovascular complications during surgery for pheochromocytoma/paraganglioma (PPGL). OBJECTIVES: We aimed to assess the risk of intraoperative HDI in patients with PPGL to improve surgical outcome. METHODS: A total of 199 consecutive patients with PPGL confirmed by surgical pathology were retrospectively included in this study. This cohort was separated into 2 groups according to intraoperative systolic blood pressure, the HDI group (n = 101) and the hemodynamic stability (HDS) group (n = 98). It was also divided into 2 subcohorts for predictive modeling: the training cohort (n = 140) and the validation cohort (n = 59). Prediction models were developed with both the ensemble machine learning method (EL model) and the multivariate logistic regression model using body composition parameters on computed tomography, tumor radiomics, and clinical data. The efficiency of the models was evaluated with discrimination, calibration, and decision curves. RESULTS: The EL model showed good discrimination between the HDI group and HDS group, with an area under the curve of (AUC) of 96.2% (95% CI, 93.5%-99.0%) in the training cohort, and an AUC of 93.7% (95% CI, 88.0%-99.4%) in the validation cohort. The AUC values from the EL model were significantly higher than the logistic regression model, which had an AUC of 74.4% (95% CI, 66.1%-82.6%) in the training cohort and an AUC of 74.2% (95% CI, 61.1%-87.3%) in the validation cohort. Favorable calibration performance and clinical applicability of the EL model were observed. CONCLUSION: The EL model combining preoperative computed tomography-based body composition, tumor radiomics, and clinical data could potentially help predict intraoperative HDI in patients with PPGL.

177 Lu-DOTATATE in the Treatment of Recurrent Pheochromocytoma With Multiple Metastases.

ABSTRACT: The treatment of metastatic pheochromocytoma is challenging. We report a case of a woman with recurrent pheochromocytoma with multiple metastases who achieved excellent response after 4 cycles of 177 Lu-DOTATATE therapy. She did not experience any observable adverse effects. Her disease was still stable 6 months after the fourth cycle of treatment.

Prospective Study of a System-Wide Adrenal Incidentaloma Quality Improvement Initiative.

BACKGROUND: Appropriate follow-up of incidental adrenal masses (IAMs) is infrequent. We implemented a quality improvement (QI) program to improve management of IAMs. STUDY DESIGN: This system-wide initiative targeted primary care providers (PCPs) after IAM detection. It incorporated (1) chart-based messages and emails to PCPs, (2) an evidence-based IAM evaluation algorithm, (3) standardized recommendations in radiology reports, and (4) access to a multispecialty adrenal clinic. Patients diagnosed with an IAM from January 1, 2018, to December 31, 2019, were prospectively included (the "QI cohort") and compared with a historical, preintervention cohort diagnosed with IAMs in 2016. The primary outcomes were the initiation of an IAM investigation by the PCP, defined as relevant clinical history-taking, laboratory screening, follow-up imaging, or specialist referral. RESULTS: The QI cohort included 437 patients and 210 in the historical cohort. All patients had 12 months or more of follow-up. In the QI cohort, 35.5% (155 of 437) met the primary endpoint for PCP-initiated evaluation, compared with 27.6% (58 of 210) in the historical cohort (p = 0.0496). Among the subgroup with a documented PCP working within our health system, 46.3% (74 of 160) met the primary endpoint in the QI cohort vs 33.3% (38 of 114) in the historical cohort (p = 0.035). After adjusting for insurance status, presence of current malignancy, initial imaging setting (outpatient, inpatient, or emergency department), and having an established PCP within our health system, patients in the QI cohort had 1.70 times higher odds (95% CI 1.16 to 2.50) of undergoing a PCP-initiated IAM evaluation. Adrenal surgery was ultimately performed in 2.1% (9 of 437) of QI cohort patients and 0.95% (2 of 210) of historical cohort patients (p = 0.517). CONCLUSIONS: This simple, moderately labor-intensive QI intervention was associated with increased IAM evaluation initiated by PCPs.

Thyroid and adrenal incidentalomas on chest CT: Prevalence, diagnostic work-up and outcomes in a cohort of COVID-19 suspected patients.

OBJECTIVE: Due to increased use of computed tomography (CT), prevalence of thyroid and adrenal incidentalomas is rising. Yet, previous studies on the outcomes of diagnostic work-up of incidentalomas are subjected to inclusion bias. Therefore, we aimed to investigate prevalence and outcomes of diagnostic work-up of thyroid and adrenal incidentalomas detected on chest CT in a less selected population of COVID-19 suspected patients. DESIGN: A retrospective, observational cohort study. METHODS: We included all COVID-19 suspected patients who underwent chest CT between March 2020 and March 2021. Radiology reports and medical records were reviewed for the presence and subsequent diagnostic work-up of thyroid and adrenal incidentalomas. RESULTS: A total of 1,992 consecutive COVID-19 patients were included (59.4% male, median age 71 years [IQR: 71-80]). Thyroid and adrenal incidentalomas were identified in 95 (4.8%) and 133 (6.7%) patients, respectively. Higher prevalence was observed with increasing age, among female patients and in patients with malignancy. Forty-four incidentalomas were further analyzed, but no malignancies were found. Only three lesions were hormonally active (1 thyrotoxicosis and 2 mild autonomous cortisol secretion). Diagnostic work-up did not lead to any change in clinical management in 97.7% of the analyzed patients. CONCLUSION: Prevalence rates of thyroid and adrenal incidentalomas on chest CT in a less selected COVID-19 cohort were 4.8% and 6.7%, respectively. Yet, as all incidentalomas turned out to be benign and only three lesions were (mildly) hormonally active, this raises the question whether intensive diagnostic work-up of incidentalomas is necessary in all patients.

Diagnostic imaging of a rare case of incidental adrenal ganglioneuroma.

A 53-year-old man complaining of pain in the right hypochondrium underwent an abdominal ultrasound that showed a left adrenal lesion. Further instrumental investigations (CT and MRI, both with contrast medium) were performed which diagnosed an adrenal ganglioneuroma, confirmed by the histological examination. The patient also underwent an endocrinological examination. The treatment was surgical and consisted of an adrenalectomy through video-laparoscopic access. Adrenal ganglioneuromas are rare tumors but well described and known in the literature. For this reason, this case report has primarily an educational purpose: the totality of the data collected (clinical, laboratoristic, instrumental, and histopathological) constituted a multidisciplinary case, with the focus on imaging.

Challenges in the diagnosis of the enigmatic primary adrenal leiomyosarcoma: two case reports and review of the literature.

BACKGROUND: Primary adrenal leiomyosarcoma is a rare and aggressive mesenchymal tumor derived from the smooth muscle wall of a central adrenal vein or its tributaries; therefore, tumors tend to invade the inferior vena cava and cause thrombosis. The great majority of tumors grow rapidly, which makes the disease difficult to diagnose in its early clinical stages and needs differentiation from adrenocortical carcinomas for the selection of chemotherapy including mitotane which causes adrenal insufficiency. CASE PRESENTATION: We presented two patients with adrenal leiomyosarcoma who were referred to our hospital with abdominal pain and harboring large adrenal tumors and inferior vena cava thrombosis. The endocrine findings, including serum catecholamine levels, were unremarkable. These two patients were considered clinically inoperable, and CT-guided core needle biopsy was performed to obtain the definitive histopathological diagnosis and determine the modes of therapy. The masses were subsequently diagnosed as primary adrenal leiomyosarcoma based on the histological features and positive immunoreactivity for SMA (smooth muscle actin), desmin, and vimentin. CONCLUSIONS: Adrenal leiomyosarcoma derived from the smooth muscle wall of a central adrenal vein or its tributaries is rare but should be considered a differential diagnosis in the case of nonfunctioning adrenal tumors extending directly to the inferior vena cava. CT-guided biopsy is considered useful for histopathological diagnosis and clinical management of patients with inoperable advanced adrenal tumors without any hormone excess.

Adrenal cortical adenoma arising in the setting of renal-adrenal fusion: a case report and review of the literature.

BACKGROUND: Renal-adrenal fusion is a rare entity resulting from incomplete encapsulation of the adrenal gland and kidney. Only 18 cases have been reported in English literature to date. CASE PRESENTATION: Our patient is a 77-year-old African American female who presented with a systolic blood pressure of 200 mmHg. Computed tomography showed an enhancing 9 × 6 cm mass anterior and medial to the left kidney. The patient underwent a left adrenalectomy with partial nephrectomy. Gross and histologic examinations revealed an adrenal cortical adenoma and renal-adrenal fusion. CONCLUSION: Renal-adrenal fusion may pose a diagnostic challenge, particularly when there is a concurrent adrenal adenoma. It is important to be aware of this uncommon anomaly to avoid misdiagnosis and overtreatment.