Shengjie Guo

Video S1 Single-port-gasless retroperitoneal laparoscopic adrenalectomy (SPG-RLA)-left side. Video S2 Single-port-gasless retroperitoneal laparoscopic adrenalectomy (SPG-RLA)-right side. Authors: Xianda Chen, Zhenhua Liu, Haichao Huang, Mingkun Chen, Lei Bian, Nan Ma, Jun Wang, Hui Han, Kai Yao, Renchun Lai, Yuhui Long, Xia Zheng, Shengjie Guo

Objective Although thermal ablation, surgery, and radiotherapy are established locoregional therapies for adrenal metastases, direct comparisons among these treatments are limited. This study aimed to compare the clinical effectiveness and safety of locoregional treatments for adrenal metastases. Materials and methods This multicenter retrospective cohort study included patients with adrenal metastases treated with locoregional therapies, including thermal ablation, surgery, or radiotherapy. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics. Local progression-free survival (LPFS), overall survival (OS), complication rates, and cost were evaluated. Nomograms for OS prediction were developed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression models. Results A total of 496 patients (median age, 57 years; 384 men) were included: surgery (n = 231), ablation (n = 132), and radiotherapy (n = 133). After IPTW adjustment, surgery and radiotherapy showed significantly improved LPFS compared with ablation (p = 0.021). Subgroup analysis demonstrated no significant differences in LPFS among treatment modalities for tumors smaller than 5 cm (p = 0.23). Regarding OS, surgery had a significantly better survival compared with ablation and radiotherapy (p = 0.004). Thermal ablation exhibited the lowest complication rates and lowest treatment cost (p < 0.001). The OS nomogram showed moderate predictive ability. Conclusions Locoregional therapy strategies for adrenal metastases should be individualized. For tumors smaller than 5 cm, thermal ablation offers local tumor control comparable to surgery and radiotherapy, while providing superior safety and lower treatment costs. Key Points QuestionDirect comparative evidence among thermal ablation, surgery, and radiotherapy for adrenal metastases is limited. How do clinical effectiveness, safety, and cost of these treatment modalities compare? FindingsFor adrenal metastases smaller than 5 cm, thermal ablation provides local control comparable to surgery and radiotherapy, while being associated with significantly fewer complications and lower treatment costs. Clinical relevanceFor patients with adrenal metastases smaller than 5 cm, thermal ablation offers a minimally invasive, safer, and less costly treatment option. It provides local tumor control comparable to surgery or radiotherapy, supporting individualized treatment selection based on tumor size. Graphical Abstract

Neutrophils are crucial immune components within the tumor microenvironment, significantly impacting tumor progression and anti-tumor immunity. To systematically characterize the heterogeneity of neutrophils in bladder cancer (BLCA), we integrated large-scale single-cell RNA sequencing (scRNA-seq) data of BLCA to define the transcriptomic landscape of neutrophil subtypes. Functional enrichment, pseudotime analysis, cell-cell communication, and deconvolution of bulk RNA sequencing (RNA-seq) samples from BLCA were conducted to comprehensively characterize the biological profiles and functions, as well as the prognostic relevance of neutrophil subtypes. A machine learning-based predictive model was developed based on the balance of prognosis-related neutrophil subtypes. We identified five distinct subtypes of neutrophils in BLCA and focused on two subtypes that were prognostically antagonistic. VEGFA+ neutrophils (Neu_0), characterized by pro-angiogenic, immunosuppressive, and extracellular matrix remodeling signatures, showed a significant correlation with poorer survival. GBP1 + neutrophils (Neu_4), characterized by response to interferon, exhibited increased innate immune activities and the production of cytokines that activate anti-tumor immunity, significantly correlated with improved survival. Pseudotime analysis positioned both Neu_0 and Neu_4 as terminal states. Cell-cell communication further identified Neu_0 as a hub orchestrating multiple pro-tumorigenic interactions. The predictive model based on the balance of Neu_0 and Neu_4 effectively stratified BLCA patients into distinct risk groups with significant differences in clinical outcomes, immune landscapes, and response profiles to antibody-drug conjugate (ADC) treatment. The investigation provided novel insights into the functional profiles of neutrophils in BLCA and offered a novel tool for guiding therapeutic strategies in BLCA.

Adrenocortical carcinoma (ACC), a rare and highly malignant adrenal gland tumor, exhibits computed tomography (CT) characteristics that resemble those of the less malignant pheochromocytoma (PHEO). While biochemical evaluation is widely accepted for differentiating between ACC and PHEO, non-functioning tumors remain a diagnostic challenge. The similarity in CT imaging and atypical hormone levels can lead to suboptimal accuracy in diagnosis, leading to inappropriate clinical interventions. This study aims to differentiate between large (≥ 4 cm) ACC and PHEO with radiomics features based on contrast-enhanced CT. In this retrospective study, 158 patients who received pathological diagnoses of ACC or PHEO between January 2011 and September 2023 were enrolled from three institutions. Radiomics features were extracted from different phases of contrast-enhanced CT and then selected by a two-step procedure. The radiomics model was developed in a cohort of 109 patients from Institution 1, then the model performance was evaluated in the external test cohort of 49 patients from Institutions 2 and 3. The area under the receiver operating characteristic curve (AUC) of the radiomics model was compared with two radiologists using the DeLong test. Hormone testing results were collected to determine the presence of excess cortisol or catecholamines. SHapley Additive exPlanations (SHAP) was used to improve the interpretability of the radiomics model. We developed and evaluated a radiomics model consisting of ten selected CT-based radiomics features. In the external test cohort, the proposed radiomics model achieved high accuracy (86%), specificity (88%), and sensitivity (81%) in differentiating between ACC and PHEO and outperformed 2 radiologists (AUC 0.920 vs. 0.786, 0.629). This radiomics model showed strong capabilities in differentiating biochemically negative ACC and PHEO (with an accuracy of 80%). Moreover, its performance remained consistent even when cortisol and catecholamine levels were simultaneously elevated. Furthermore, SHAP provided quantitative explanations for the radiomics model and visualized the diagnostic process. The interpretable CT-based radiomics model outperforms radiologists in differentiating between ACC and PHEO, especially when hormone testing results are atypical.

PurposeAdrenal metastasectomy is a common local treatment for adrenal metastases, with a lack of serum prognostic factors. Here, we identified the prognostic significance of preoperative hemoglobin and albumin levels in patients undergoing adrenal metastasectomy.Materials and MethodsData from 93 patients who underwent adrenal metastasectomy were assessed retrospectively. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values of hemoglobin and albumin for survival. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method, thereafter Cox regression models and subgroup analyses were applied to adjust confounding factors. A risk stratification developed by joint use of serum hemoglobin and albumin levels was also tested.ResultsOptimal cut-off points were 130.5 g/L and 44.8 g/L for hemoglobin and albumin, respectively. Multivariate Cox regression analysis identified decreased hemoglobin (HR [95% CI]: 0.41 [0.18-0.91], P = 0.029) and albumin (HR [95% CI]: 0.12 [0.02-0.88], P = 0.038) levels as independent factors for poorer OS. Patient with both decreased hemoglobin and albumin levels had the worst OS (P = 0.001) and DFS (P = 0.001) than other risk groups. Subgroup analyses proved decreased hemoglobin and albumin levels predicted poorer OS independent of cancer types.ConclusionsPreoperative hemoglobin and albumin levels may serve as prognostic predictors after adrenal metastasectomy. A prognostic model that combines hemoglobin and albumin can improve accuracy in predicting patient outcomes and be easily implemented in clinical practice.

Single-port laparoscopic adrenalectomy is a minimally invasive surgical approach, characterized by fewer incisions and reduced pain¹. Meanwhile, gasless laparoscopy may provide advantages for certain procedures compared with conventional laparoscopy using pneumoperitoneum².

The disparate distribution of data across medical centers represents a significant challenge to the development of generalized machine learning models. Furthermore, data in the medical field are typically limited and imbalanced, making it more difficult for traditional domain adaptation methods to learn shared knowledge across disparate hospital data sets, further leading to poor generalization ability of the model in the target domain. In this paper, we propose a SFI (Shapley-based Feature Importance) Driven Rapid Distribution Alignment method for classification, aimed at identifying a potential low-dimensional feature space to rapidly align the distribution of the source domain and the target domain on small sample data. First, the feature importance calculated from the Shapely value guides the Conditional Tabular Generative Adversarial Network (CTGAN) algorithm to augment the small sample data and provide a more precise characterization of the data distribution. Then, feature elimination based on Shapely values and harmony are combined to align data distribution from different hospitals. In contrast to existing traditional domain adaptation techniques that solely prioritize reducing discrepancies in feature distributions across diverse domains, our approach additionally considers the significance of features in classification. The effectiveness of our method was finally verified through the classification of adrenal tumors in a small multi-center sample.

Introduction: Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC‐A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen. Methods: Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC‐A measurements in 2014–2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC‐A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors. Results: Eighty patients were included. LCGM models identified two distinct trajectories of SCC‐A: low‐stable (40%; n = 32) and high‐decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23–10.53], p = 0.019), progression‐free survival (HR [95% CI]: 11.33 [3.19–40.3], p < 0.001), objective response rate (37.5% vs. 62.5% p = 0.028), disease control rate (60.4% vs. 96.9% p < 0.00), and pathological complete response rate (21.2% vs. 51.9%, p = 0.014) were significantly worse in the high‐decline arm. Conclusion: PC patients' SCC‐A change rate was associated with tumor response and patient survival after TIP chemotherapy. SCC‐A might assist tumor monitoring after systemic therapies.

Background: Radical inguinal lymph node dissection (rILND) is the most available treatment to cure penile cancer (PC) with limited inguinal-confined disease. However, guidelines regarding acceptable boundaries of rILND are controversial, and consensus is lacking. The authors aimed to standardize the surgical boundaries of rILND with definite pathological evidence and explore the distribution pattern of inguinal lymph nodes (ILNs) in PC. Methods: A total of 414 PC patients from two centers who underwent rILND were enrolled. The ILN distribution was divided into seven zones anatomically for pathological examination. Student’s t test and Kaplan–Meier survival analysis were used. Results: ILNs displayed a funnel-shaped distribution with high density in superior regions. ILNs and metastatic nodes are present anywhere within the radical boundaries. Positive ILNs were mainly concentrated in zone I (51.7%) and zone II (41.3%), but there were 8.7% and 12.3% in inferior zones V and VI, respectively, and 7.1% in the deep ILNs. More importantly, a single positive ILN and first-station positive zone was detected in all seven regions. Single positive ILNs were located in zones I through VI in 40.4%, 23.6%, 6.7%, 18.0%, 4.5%, and 1.1%, respectively, and 5.6% presented deep ILN metastasis directly. Conclusions: The authors established a detailed ILN distribution map and displayed lymphatic drainage patterns with definite pathological evidence using a large cohort of PC patients. Single positive ILNs and first-station metastatic zones were observed in any region, even directly with deep ILN metastasis. Only rILND can ensure tumor-free resection without the omission of positive nodes.

Background: Penile squamous cell carcinoma (PSCC) is a human papillomavirus (HPV)‐associated malignancy. Immunotherapy is emerging as a potential treatment for advanced PSCC. In this study, the authors analyzed the association of HPV status with outcomes and the immune microenvironment in patients with advanced PSCC undergoing programmed cell death protein 1 (PD1) inhibitor–based combination therapy (PCT).Methods: HPV status was assessed using quantitative polymerase chain reaction in 87 patients with advanced PSCC treated with PCT. Objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS) in the HPV+ and HPV– groups were compared. Additionally, bulk RNA sequencing was performed to investigate the potential impact of HPV on the immune microenvironment in advanced PSCC.Results: Among patients receiving first‐line PCT, ORR (91.7% vs. 64.6%, p = .014) and DCR (100.0% vs. 79.2%, p = .025) in the HPV+ group were higher compared to the HPV– group. Kaplan–Meier curves demonstrated that the HPV+ group exhibited superior PFS (p = .005) and OS (p = .004) for patients in the first‐line setting. However, these advantages of HPV infection were not observed in multi‐line PCT (p > .050). HPV status remained an independent prognostic factor for predicting better ORR (p = .024), PFS (p = .002), and OS (p = .020) in the multivariate analyses. Landmark analyses showed that the HPV‐induced superiority of PFS occurred at an early stage (within 3 months) and OS occurred at a relatively late stage (within 9 months). Bioinformatic analyses identified potential immune‐activated genes (GLDC, CYP4F12, etc.) and pathways (RAGE, PI3K/AKT, etc.), antitumor immune cell subtypes, and lower tumor immune dysfunction and exclusion scores in HPV+ tissues.Conclusions: HPV infection may confer treatment efficacy and survival benefits in patients with advanced PSCC receiving first‐line PCT because of the possible stimulation of the antitumor immune microenvironment.Plain Language Summary: Human papillomavirus (HPV) infection may induce better objective response rate, progression‐free survival (PFS), and overall survival (OS) for advanced penile squamous cell carcinoma (PSCC) patients receiving first‐line programmed cell death protein 1 inhibitor–based combination therapy (PCT) instead of multi‐line PCT. HPV infection‐induced PFS advantage occurs at an early stage (within 3 months) whereas OS superiority occurs at a relatively late stage (within 9 months). Antitumor immune microenvironment could be stimulated by HPV infection in advanced PSCC tissues.