Special issue "The advance of solid tumor research in China": 68Ga-PSMA-11 PET/CT for evaluating primary and metastatic lesions in different histological subtypes of renal cell carcinoma.

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 68 Ga-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 68 Ga-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 68 Ga-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). 68 Ga-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 68 Ga-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.

Tumor necrosis as a poor prognostic predictor on postoperative survival of patients with solitary small hepatocellular carcinoma.

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.

Therapeutic hypothermia (different depths, durations, and rewarming speeds) for acute ischemic stroke: a meta-analysis.

OBJECTIVES: Whether therapeutic hypothermia benefits patients with acute ischemic stroke (AIS) remains controversial. The aim of this study was to evaluate the efficacy and safety of the different depths, durations, and rewarming speeds of therapeutic hypothermia for AIS. METHODS: The MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) of therapeutic hypothermia for AIS from the inception of the databases to October 2013. After data extraction and quality assessment, a meta-analysis was performed using RevMan 5.1. RESULTS: A total of 6 RCTs involving 252 AIS patients were eligible for the meta-analysis. Subanalyses stratified by depth, duration, and rewarming speed of therapeutic hypothermia were also performed. Our results showed that therapeutic hypothermia was associated with an increased risk of pneumonia (risk ratio = 3.30, 95% CI 1.48-7.34; P = .003, P for heterogeneity = .91, I(2) = 0%). No significant difference was observed between the 2 groups in terms of neurologic outcomes, mortality, and other complications including symptomatic or fatal intracranial hemorrhage, deep vein thrombosis, and atrial fibrillation. CONCLUSIONS: These limited data suggest that therapeutic hypothermia does not significantly improve stroke outcomes and may lead to higher rates of pneumonia. Multicenter RCTs with larger samples are needed to confirm the current findings.

Angioimmunoblastic T-cell lymphoma involving the nasopharynx: An easily misdiagnosed disease with atypical histopathological features.

OBJECTIVES: To explore the clinicopathologic features, treatment, and survival outcomes of angioimmunoblastic T-cell lymphoma (AITL) involving the nasopharynx. METHODS: We retrospectively analyzed 73 cases of AITL. Among them, 64 cases with complete pre-treatment 18F-FDG positron emission tomography/computed tomography (PET/CT) images were integrated into the analysis of clinical characteristics and PET/CT findings of AITL involving the nasopharynx; 14 cases with both biopsies from lymph node and nasopharynx were included in the comparison of pathological characteristics of AITL in the two areas. Forty-six of the 73 patients who received first-line systemic treatment at our institute were included in the treatment efficacy and survival analyses. RESULTS: Nasopharyngeal involvement was seen in 44/64 (68.8%) patients. Histologically, lymph node and nasopharyngeal biopsies in 14 patients both showed small to medium-sized tumor cells, complex inflammatory infiltration, and Reed-Sternberg-like cells or B immunoblasts. However, tumor cells with clear cytoplasm, significant high endothelial venule (HEV) hyperplasia, and perivascular infiltration were observed in 5/14, 3/14, and 2/14 nasopharyngeal biopsies, respectively, but in all fourteen lymph node biopsies (P < 0.05). Immunophenotypic profiles and gene rearrangements were highly concordant. Treatment efficacy and survival were similar between patients with nasopharyngeal involvement and those without (P > 0.05), indicating nasopharyngeal involvement is not a prognostic factor for AITL patients. CONCLUSIONS: Nasopharyngeal involvement is common in AITL but can be easily misdiagnosed because of its atypical pathologic pattern, especially when a lymph node biopsy is unavailable. However, the patient's clinical presentation, PET/CT manifestations, the typical immunophenotype, and gene rearrangements help the diagnosis.

UBE2S as a novel ubiquitinated regulator of p16 and ß-catenin to promote bone metastasis of prostate cancer.

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 ß-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 ß-catenin via K11-linked ubiquitination, suggesting that it may serve as a multipotent target for metastatic PCa treatment.

A new horizon in risk stratification of hepatocellular carcinoma by integrating vessels that encapsulate tumor clusters and microvascular invasion.

BACKGROUND: Vessels that encapsulate tumor clusters (VETC) is a novel described vascular pattern different from microvascular invasion (MVI) for patients with hepatocellular carcinoma (HCC). The prognostic value of integrating VETC and MVI (VETC-MVI model) in HCC patients after resection remains unclear. METHODS: From January 2013 to December 2016, 498 HCC patients who underwent curative resection were enrolled from five academic centers and stratified into different groups according to their VETC and MVI statuses. Overall survival (OS), disease-free survival (DFS), and early and late recurrence rates were evaluated. RESULTS: The patients were divided into four subgroups: VETC-/MVI- (n = 277, 55.6%), VETC-/MVI+ (n = 110, 22.1%), VETC+/MVI- (n = 53, 10.6%), and VETC+/MVI+ (n = 58, 11.6%). The patients in the VETC+/MVI- and VETC-/MVI+ groups had similar long-term outcomes (OS: p = 0.402; DFS: p = 0.990), VETC-/MVI- patients showed the best prognosis, and VETC+/MVI+ patients had the worst prognosis. Further analysis revealed that the VETC-MVI model showed a similar stratification ability for early recurrence but not for late recurrence. The area under the curve values for early recurrence was 0.70, 0.63 and 0.64 for the VETC-MVI model, VETC, and MVI, respectively (VETC-MVI model vs VETC: p < 0.001; VETC-MVI model vs MVI: p = 0.004; VETC vs MVI: p = 0.539). Multivariate Cox regression analysis showed that the VETC-MVI model successfully predicted OS, DFS and early recurrence. CONCLUSIONS: VETC status provides additional discriminative information for patients with either MVI- or MVI+. A combination of VETC and MVI may help classify subtypes and predict the prognosis of HCC patients.

Smoking behavior and smoking index as prognostic indicators for patients with esophageal squamous cell carcinoma who underwent surgery: A large cohort study in Guangzhou, China.

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.

ASTN1 is associated with immune infiltrates in hepatocellular carcinoma, and inhibits the migratory and invasive capacity of liver cancer via the Wnt/ß­catenin signaling pathway.

Astrotactin 1 (ASTN1) is known to serve a physiological role in neuronal migration; however its role in liver cancer remains to be determined. In the present study, ASTN1 levels were lower in liver cancer tissues compared with those in matching normal tissue. ASTN1 levels were negatively associated with microscopic vascular invasion, advanced clinical stage and a less favorable prognosis in patients with hepatocellular carcinoma (HCC). Furthermore, ASTN1 overexpression in a liver cancer cell line reduced the migratory and invasive capacity of the cells. Based on bioinformatics analysis, ASTN1 levels were negatively associated with the Wnt signaling pathway. In addition, ASTN1 downregulated the protein expression levels of ß­catenin, T­cell factor (TCF)1, TCF4, Jun proto­oncogene (C­jun), Myc proto­oncogene (C­myc), cyclooxygenase­2 (COX2), metalloproteinase (MMP)2, MMP9 and vascular endothelial growth factor (VEGF) protein levels, indicative of suppression of Wnt signaling. Furthermore, XAV939­induced Wnt signaling suppression reversed the ASTN1­mediated inhibition of invasion and migration in cells. Overexpression of ASTN1 in xenografts reduced cancer development as well as Wnt signaling. TIMER analysis showed that ASTN1 expression was negatively correlated with B cell, macrophage and neutrophil infiltrating levels in HCC. Together, the results of the present study showed that ASTN1 reduced the migratory and invasive capacity of liver cancer cells, potentially served as a candidate biomarker for diagnosis and prediction of the prognosis of HCC, and was associated with immune infiltration. Understanding the underlying mechanisms of action of ASTN1 may facilitate the development of novel strategies for prevention and treatment of liver cancer.