Background: Small hepatocellular carcinoma (sHCC) is a special subtype of HCC with the maximum tumor diameter ≤ 3 cm and excellent long-term outcomes. Surgical resection or radiofrequency ablation provides the greatest chance for cure; however, many patients still undergo tumor recurrence after primary treatment. To date, there is no clinical applicable method to assess biological aggressiveness in solitary sHCC. Methods: In the current study, we retrospectively evaluated tumor necrosis of 335 patients with solitary sHCC treated with hepatectomy between December 1998 and 2010 from Sun Yat-sen University Cancer Center. Results: The presence of tumor necrosis was observed in 157 of 335 (46.9%) sHCC patients. Further correlation analysis showed that tumor necrosis was significantly correlated with tumor size and vascular invasion (P = 0.026, 0.003, respectively). The presence of tumor necrosis was associated closely with poorer cancer-specific overall survival (OS) and recurrence-free survival (RFS) as evidenced by univariate (P < 0.001; hazard ratio, 2.821; 95% CI, 1.643-4.842) and multivariate analysis (P = 0.005; hazard ratio, 2.208; 95% CI, 1.272-3.833). Notably, the combined model by tumor necrosis, vascular invasion and tumor size can significantly stratify the risk for RFS and OS and improve the ability to discriminate sHCC patients' outcomes (P < 0.0001 for both). Conclusions: Our results provide evidence that tumor necrosis has the potential to be a parameter for cancer aggressiveness in solitary sHCC. The combined prognostic model may be a useful tool to identify solitary sHCC patients with worse outcomes.

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Bone metastasis is the main site of metastasis and causes the most deaths in patients with prostate cancer (PCa). The mechanism of bone metastasis is complex and not fully clarified. By RNA sequencing and analysing key pathways in bone metastases of PCa, we found that one of the most important characteristics during PCa bone metastasis was G1/S transition acceleration caused by low protein levels of p16INK4a (p16). Interestingly, we demonstrated that UBE2S bound and degraded p16 through K11- rather than K48- or K63-linked ubiquitination, which accelerated PCa tumour cell G1/S transition in vivo and in vitro . Moreover, UBE2S also stabilized β-catenin through K11-linked ubiquitination, leading to enhanced migration and invasion of tumour cells in PCa bone metastasis. Based on our cohorts and public databases, UBE2S was overexpressed in bone metastases and positively correlated with a high Gleason score, advanced nodal metastasis status and poor prognosis in PCa. Finally, targeting UBE2S with cephalomannine inhibited proliferation and invasion in vitro , and bone metastasis of PCa in vivo . This study innovatively discovered that UBE2S plays an oncogenic role in bone metastasis of PCa by degrading p16 and stabilizing β-catenin via K11-linked ubiquitination, suggesting that it may serve as a multipotent target for metastatic PCa treatment.

Conventional imaging examinations are not sensitive enough for the early detection of recurrent or metastatic lesions in renal cell carcinoma (RCC) patients. We aimed to explore the role of 68Ga‐prostate specific membrane antigen (PSMA)‐11 positron emission tomography (PET)/computed tomography (CT) in the detection of primary and metastatic lesions in such patients. We retrospectively analyzed 50 RCC patients who underwent 68Ga‐PSMA‐11 PET/CT from November 2017 to December 2020. We observed a higher median accuracy and tumor‐to‐background maximum standard uptake value (SUVmax) ratio (TBR) of 68Ga‐PSMA‐11 PET/CT in clear cell RCC (ccRCC; 96.57% and 6.00, respectively) than in non‐clear cell RCC (ncRCC; 82.05% and 2.99, respectively). The accuracies in detecting lesions in the renal region, bone, lymph nodes and lungs in ccRCC were 100.00%, 95.00%, 98.08% and 75.00%, respectively, and those in the renal region, bone and lymph nodes in ncRCC were 100.00%, 86.67% and 36.36%, respectively. The median TBRs of the lesions from the above locations were 0.38, 10.96, 6.69 and 13.71, respectively, in ccRCC and 0.13, 4.02 and 0.73, respectively, in ncRCC. The PSMA score evaluated with immunohistochemistry was correlated with the SUVmax (P = .046) in RCC. Higher PSMA scores were observed in ccRCC than in ncRCC (P = .031). 68Ga‐PSMA‐11 PET/CT resulted in changes in clinical management in 12.9% (4/31) of cases because of the discovery of new metastases not detected with conventional imaging. These results indicate that 68Ga‐PSMA‐11 PET/CT is a promising method for the detection of metastatic lesions in ccRCC, especially for those in the bone and lymph nodes.

INTRODUCTION This study aimed to evaluate the association between smoking and smoking index with clinical outcomes of esophageal squamous cell carcinoma patients. METHODS This is a retrospective analysis conducted on consecutive patients with esophageal carcinoma who underwent esophagectomy from January 2005 to December 2010. All patients had pathologically confirmed esophageal squamous cell carcinoma. The association between smoking and sociodemographic characteristics with overall survival and disease-free survival was analyzed. Serum carcinoembryonic antigen was measured using an electrochemiluminescence immunoassay. RESULTS A total of 944 patients were enrolled. Kaplan-Meier analysis indicated that esophageal squamous cell carcinoma patients who smoked had a significantly worse prognosis in terms of both overall survival (p=0.007) and disease-free survival (p= 0.010). Multivariate analysis demonstrated that age (p=0.001), carcinoembryonic antigen (p=0.012), tumor-node-metastasis (TNM) staging (p<0.001) and smoking (p=0.048) were independently correlated with overall survival, while only TNM stage (p<0.001) and smoking (p=0.041) were identified as independent factors of disease-free survival. We divided the smoking population into two groups (smoking index <400 and ≥400). Kaplan-Meier survival analysis indicated that a smoking index <400 was associated with a significantly better prognosis in terms of both overall survival (p=0.003) and favorable disease-free survival (p=0.032). Multivariate analysis showed that age (p<0.001), TNM staging (p<0.001), and smoking index (p=0.025) were independent factors of overall survival, whereas for disease-free survival, only TNM stage (p=0.001) and smoking index (p=0.025) were identified. CONCLUSIONS Overall survival was significantly associated with smoking in esophageal squamous cell carcinoma patients. For esophageal squamous cell carcinoma patients who smoke, a higher smoking index is associated with worse clinical outcomes. Therefore, smoking may be used as a predictive indicator for pretreatment evaluation and adjustment of treatment regimen.