Objective:To investigate the genetic mutation characteristics of patients with bilateral macronodular adrenocortical disease（BmacAD）and to analyze the clinical phenotypes and adrenal nodule transcriptomic profiles associated with different genotypes.Methods:This retrospective study analyzed the clinical data of 37 patients diagnosed with BmacAD by clinical and pathological assessment who underwent surgery at Peking Union Medical College Hospital from January 2001 to December 2024. Data included symptoms and signs related to hypercortisolism，24-hour urinary free cortisol，plasma adrenocorticotropic hormone（ACTH），and overnight low-dose dexamethasone suppression test results. Whole-exome sequencing（WES）was performed on frozen adrenal hyperplasia tissue samples from surgical specimens and matched frozen residual blood samples for all patients to screen for germline and somatic mutations. Sanger sequencing was used to validate some of the identified mutations. The relation between genetic mutations and clinical features was analyzed. Transcriptome sequencing of the hyperplastic tissues was conducted，and unsupervised clustering，differential gene expression analysis，and pathway enrichment analysis were used to compare the transcriptomic profiles of patients with different genotypes.Results:A total of 37 cases were included（23 males and 14 females），aged between 31?68 years old. Among the patients with available clinical data，most exhibited signs of hypercortisolism，including hypertension（100.0%，36/36），diabetes（50.0%，18/36），and centripetal obesity（55.9%，19/34），accompanied by relevant endocrine abnormalities such as elevated 24-hour urinary free cortisol（79.4%，27/34），suppressed ACTH（77.8%，28/36），and a positive overnight low-dose dexamethasone suppression test（45.2%，14/31）. WES and Sanger sequencing revealed that ARMC5 gene mutations were the most common. Among the 37 patients，33（89.2%）had ARMC5 germline mutations，and 31（83.8%）concurrently harbored ARMC5 somatic mutations，including 3 cases of loss of heterozygosity. Two patients without detectable ARMC5 mutations both carried a somatic p.S45P mutation in the CTNNB1 gene and neither had typical manifestations of hypercortisolism. Transcriptome sequencing results suggested that patients with ARMC5 mutations had an upregulation of pathways related to steroid secretion.Conclusions:The majority of BmacAD patients present with typical manifestations of hypercortisolism，while a minority exhibit only mild autonomous cortisol secretion without obvious symptoms. Biallelic inactivation of the ARMC5 gene is the primary genetic driver of this disease，leading to more severe hypercortisolism by upregulating steroid hormone secretion. CTNNB1 mutations may be involved in the pathogenesis of some patients without ARMC5 mutations.

Objective:To investigate the genetic mutation characteristics of patients with bilateral macronodular adrenocortical disease（BmacAD）and to analyze the clinical phenotypes and adrenal nodule transcriptomic profiles associated with different genotypes.Methods:This retrospective study analyzed the clinical data of 37 patients diagnosed with BmacAD by clinical and pathological assessment who underwent surgery at Peking Union Medical College Hospital from January 2001 to December 2024. Data included symptoms and signs related to hypercortisolism，24-hour urinary free cortisol，plasma adrenocorticotropic hormone（ACTH），and overnight low-dose dexamethasone suppression test results. Whole-exome sequencing（WES）was performed on frozen adrenal hyperplasia tissue samples from surgical specimens and matched frozen residual blood samples for all patients to screen for germline and somatic mutations. Sanger sequencing was used to validate some of the identified mutations. The relation between genetic mutations and clinical features was analyzed. Transcriptome sequencing of the hyperplastic tissues was conducted，and unsupervised clustering，differential gene expression analysis，and pathway enrichment analysis were used to compare the transcriptomic profiles of patients with different genotypes.Results:A total of 37 cases were included（23 males and 14 females），aged between 31?68 years old. Among the patients with available clinical data，most exhibited signs of hypercortisolism，including hypertension（100.0%，36/36），diabetes（50.0%，18/36），and centripetal obesity（55.9%，19/34），accompanied by relevant endocrine abnormalities such as elevated 24-hour urinary free cortisol（79.4%，27/34），suppressed ACTH（77.8%，28/36），and a positive overnight low-dose dexamethasone suppression test（45.2%，14/31）. WES and Sanger sequencing revealed that ARMC5 gene mutations were the most common. Among the 37 patients，33（89.2%）had ARMC5 germline mutations，and 31（83.8%）concurrently harbored ARMC5 somatic mutations，including 3 cases of loss of heterozygosity. Two patients without detectable ARMC5 mutations both carried a somatic p.S45P mutation in the CTNNB1 gene and neither had typical manifestations of hypercortisolism. Transcriptome sequencing results suggested that patients with ARMC5 mutations had an upregulation of pathways related to steroid secretion.Conclusions:The majority of BmacAD patients present with typical manifestations of hypercortisolism，while a minority exhibit only mild autonomous cortisol secretion without obvious symptoms. Biallelic inactivation of the ARMC5 gene is the primary genetic driver of this disease，leading to more severe hypercortisolism by upregulating steroid hormone secretion. CTNNB1 mutations may be involved in the pathogenesis of some patients without ARMC5 mutations.

Objective:To analyze the clinical features of adrenal metastases and summarize the experience of diagnosis and treatment.Methods:The clinicopathological data of 210 patients with adrenal metastases admitted to Peking Union Medical College Hospital from Jan. 1990 to Jun. 2021 were retrospectively analyzed, and the relevant literature was reviewed. The clinical characteristics, primary tumor types, imaging examination methods and diagnosis and treatment methods of adrenal metastases were summarized.Results:Among 210 patients, 153 were males and 57 were females, with an average age of (60±12) years. The average maximum diameter of the tumor was (4.7±2.6) cm, the maximum was 14.5 cm, and the minimum was 0.5 cm. Tumor occurred in 84 cases on the left, 81 cases on the right, and 44 cases bilateral. The primary tumors of 210 patients were 72 cases of lung cancer, 48 cases of renal cancer, 29 cases of hepatobiliary cancer, 18 cases of colorectal cancer, 11 cases of gastric esophageal cancer, 6 cases of pancreatic cancer, 5 cases of breast cancer, 3 cases of melanoma, and 18 cases of other tumors. 108 patients had no obvious clinical symptoms of discomfort, only found in the review of primary tumor or routine physical examination. 102 were primary disease-related symptoms, and 210 patients had no abnormal endocrine signs such as moon face and buffalo back. The median time from diagnosis of primary tumor to adrenal metastasis was 3 months. 95 cases were diagnosed with primary tumor at the same time. The longest time was 228 months. Of the 210 patients, 203 underwent CT, 99 PET-CT, 74 B-ultrasound and 25 MRI. A total of 122 patients were clinically diagnosed as adrenal metastasis by history and imaging examination. One patient was treated with adrenal photon knife, one patient was treated with adrenal artery embolization chemotherapy, and 21 patients were treated with adrenal radiotherapy or CT-guided adrenal radiofrequency ablation. A total of 88 patients were diagnosed as adrenal metastasis by histopathology. Among them, 12 patients were diagnosed by adrenal puncture under CT guidance, 74 patients were diagnosed by adrenal surgery, and 2 patients were further treated with metastatic tumor resection after adrenal metastasis was diagnosed by puncture. Finally, all patients were diagnosed as adrenal metastasis of malignant tumor by pathology, and they continued to be treated with primary tumor.Conclusions:Lung cancer is the most common type of primary adrenal metastases in our hospital. Most of the elderly men have no obvious endocrine-related symptoms and signs. CT is an effective means of examination, supplemented by B ultrasound or MRI diagnostic accuracy will be further improved, but the diagnosis still depends on histopathological examination. For patients with isolated adrenal metastasis, surgical treatment can significantly improve the prognosis. However, comprehensive treatment should be carried out according to the general situation of patients, the type and biological behavior of primary tumors, and the characteristics of metastatic tumors, so as to achieve the best curative effect.

Objective:To evaluate the performance of a novel master-slave transurethral surgical robot system and test its safety and effectiveness.Methods:In September 2021, two urologists (A and B) applied transurethral surgery robot prototype on simulate human tissue model experiments. The transurethral surgical robotic systems used in this study include: master-end control platform, slave-end surgical platform, and end-effector. The main end control platform adopted Omega7 force feedback main hand as the main controller, and the degrees of freedom include: up and down translation, left and right translation, front and back translation, end rotation, end pitch, end swing, end operation. The end-operated surgical platform adopts the Med 7 seven-degree-of-freedom medical collaborative robotic arm to apply precision through the end effector operated resectoscope. The end effectors were modular in design for maximum compatibility with existing surgical instruments. The two doctors routinely assembled the resectoscope and the transurethral surgical robot 20 times each to calculate the assembly time. The routine assembly time of the resectoscope included the time when the lens and light source were connected after the resectoscope had been installed, and the doctor entered the experimental module with the resectoscope in hand. The time to assemble the surgical robot included the time to install the resectoscope with the end effector and connect the lens and light source to enter the experimental module. Two doctors performed 25 simulated prostate resection and 5 simulated bladder resection procedures. The small intestine, heart and stomach of pigs were sutured to construct urethra, prostate and bladder structures that simulated human body: urethra (pig small intestine) was 16-18 cm long, prostate (pig heart) size was about 5 cm×5 cm×6 cm, and bladder (pig stomach) capacity was 250-300 ml. The model was placed in a 3D printed sleeve to simulate the fitting of the urethra to the silicone penis. Prostate resection surgery: the doctor operated the handle on the main end control platform, controld the slave actuator through human-computer interaction, and excisesed the "prostate" around the fixed point under direct vision, simulating standard transurethral prostatectomy, the resection ranges from the bladder neck to the tip of the prostate, and the two lobes and middle lobes were removed. Each operation lasted 40 minutes and the weight of the removed tissue was recorded. Transurethral esection of the bladder: each procedure involved removal of the triangle, bilateral walls, and apical area of the bladder to record the occurrence of perforation. The accuracy of master-slave operating distance, operation attitude accuracy, master-slave operation attitude repeatability, fixed point accuracy, master-slave control start delay time and master-slave control following delay time, robotic arm swing range, limit site and other indicators of the robot were verified by surgery.Results:The positioning accuracy of the end effector of transurethral surgical robot was less than 0.5 mm, the accuracy of master-slave operation distance was ≤0.5 mmthe repeatability distance was ≤0.2 mm, the accuracy of master-slave operation attitude was a≤0.30°, the angle b≤0.30°, the angle C≤0.15°, the accuracy of the fixed point ≤is 0.6 mm, the maximum activity space of the robotic arm was a hemispherical space with a radius of (1 493±5)mm. The delay time of master-slave control startup and master-slave control follow-up delay time did not exceed 100ms; When the end of the manipulator was collided by an external force during the movement, the system could automatically stop the movement of the manipulator, at this time the external force was(70±7) N, and the fixed point setting range was 30-170 mm. The assembly time of transurethral surgery robot by Doctor A and Doctor B was (111.35±57.88) s and (111.70±58.30), respectively.The time of routine assembly resectoscope was (44.90±4.89) s and (44.90±5.16) s, respectively, and the difference between the routine assembly time and robot assembly time of Doctor A and Doctor B were not statistically significant( P=0.679 and P=0.996), the assembly time of the two doctor robots was more than the conventional assembly time( P=0.001 and P=0.001). The average weight of prostate tissue resection in experiments was (43.60±12.42)g and (43.45±12.63)g, respectively. No significant difference was found between them( P=0.954). During the simulated bladder electrosurgery, the robot system could successfully complete the resection of the triangular region, bilateral walls, and top tissues of the bladder. In the surgical experiment, the system operated smoothly, without mechanical failure, module damage, perforation, and other complications. Conclusions:The transurethral surgery robot might be a choice for transurethral surgery.

Objective To evaluate the effect of mitotane as a preoperative adjuvant therapy in advanced adrenocortical carcinoma.Methods Mitotane was used in 2 patients as preoperative adjuvant therapy.Case 1,a 24-year-old woman had Cushing's symptom for 1 year and presented with edema in both legs for 1 month.Computed tomography (CT) showed a solid mass in the right adrenal.It was about 10.0 cm×7.8 cm with calcification,and the boundary of tumor was not clear.Enhanced CT scan showed heterogeneous enhancement and there was a suspicious filling defect in the inferior vena cava.Biopsy of adrenal neoplasm was made and pathological result was adrenocortical tissue.The patient was diagnosed as right adrenocortical carcinoma with tumor thrombus in vena cava.Mitotane was used for 6 months.Case 2,a 42-year-old woman who underwent left adrenal adenoma resection 9 years ago,presented with Cushing's syndrome for 2 years,and found masses in left retroperitoneal and abdominal wall for 6 months.CT showed multiple nodular soft tissues with pitting calcification and fusion in it,locating between retroperitoneal spleen and kidney.The biggest section was approximately 8 cm× 12 cm,with a largest diameter of 14 cm.Enhanced scan showed uneven density wiht CT value of about 32 HU.Nodule shadows which were obviously strengthened were found in front of the right side of the diaphragmatic muscle.And some heterogeneous enhanced nodule shadows could be seen in front of the right abdominal peritoneal and muscle layer.The patient was diagnosed as right adrenocortical carcinoma with multiple metastases.Mitotane was used for treatment for 5 months.Results Both of their Cushing's symptom were significantly improved by taking drugs.The main side effects were nausea,vomiting,dizziness,fatigue,diarrhea and so on,but all could be alleviated after drug dosage adjustment.CT reexamination showed the volume of the primary lesion and metastases were significantly reduced.The postoperative pathological report after remove of the tumor and metastases showed adrenocortical carcinoma.Followed up for 42 and 7 months,the patients had no recurrence.Conclusions Mitotane is effectiveas preoperative adjuvant therapy in adrenocortical carcinoma and metastases.It can reduce the lesions significantly,relieve the Cushing's symptom,and provide opportunity for surgical treatment.