基于CT图像的评分模型预测食管鳞癌喉返神经旁淋巴结转移风险

目的:基于原发肿瘤及淋巴结CT特征建立评分模型预测食管鳞癌患者喉返神经旁淋巴结(RLN-LN)转移风险。方法:回顾性收集2014年1月至2019年12月于北京大学肿瘤医院行食管癌根治术并清扫RLN-LN的92例食管鳞癌患者。根据术后淋巴结病理结果分为RLN-LN转移组(n=37)和非转移组(n=55)。评估术前CT图像,记录食管癌患者年龄、性别、分化程度、肿瘤位置、肿瘤大小(肿瘤长度、肿瘤厚度、厚度/长度)、RLN-LN大小(淋巴结短径、长径、短径/多平面重建(MPR)最长径]。采用多元logistic回归筛选独立预测因子并建立评分模型,采用ROC曲线评估评分模型及独立预测因子诊断RLN-LN转移的效能,采用Z检验比较曲线下面积(AUC)的差异。应用Hosmer-Lemeshow检验和校准曲线评估模型拟合度。结果:肿瘤位置、肿瘤长度、RLN-LN短径、短径/MPR最长径是RLN-LN转移的独立预测因子,其诊断RLN-LN转移的AUC分别为0.586、0.705、0.831、0.777。基于以上4个CT特征建立评分模型,评分模型诊断RLN-LN转移的AUC为0.903(95%CI 0.846~0.959),优于各单一CT特征(Z=5.812,P<0.001;Z=2.161,P=0.030;Z=2.929,P=0.003;Z=4.052,P<0.001)。拟合优度Hosmer-Lemeshow检验结果显示P=0.555,校准曲线提示评分模型预测RLN-LN转移风险与实际转移风险之间具有良好的一致性。结论:基于CT图像的评分模型有助于食管鳞癌RLN-LN转移状态危险分层。     

Metastasis of oral squamous cell carcinoma to the parotid lymph nodes

Parotid lymph node (PLN) metastasis greatly worsens the prognosis of patients with oral squamous cell carcinoma (OSCC) and poses a great challenge for further treatment of OSCC. The clinicopathological characteristics and treatment strategies for PLN metastasis from OSCC need to be comprehensively elucidated. A retrospective review of OSCC patients who experienced postoperative PLN metastasis in our department between 2000 and 2018 was performed in this study. A total of 47 OSCC patients with postoperative PLN metastasis were identified. PLN with metastasis were divided into three groups based on the location: parotid tail (PLN-t), superficial lobe (PLN-sl), and deep lobe (PLN-dl). Most of the patients experienced PLN metastasis within less than 12 months after the primary surgery for OSCC. Comparatively, patients with PLN-sl metastasis were more prone to have infiltration of the facial nerve. The tongue and buccal mucosa were the most frequent primary sites associated with PLN metastasis from OSCC. PLNs in the parotid tail were most commonly affected by the metastasized OSCC. Consequently, we recommend a series of strategies for the prevention and treatment of PLN metastasis for OSCC patients. In conclusion, PLNs should not be overlooked during preoperative evaluation and postoperative follow-up examinations for OSCC patients.     

The impact of delayed diagnosis on the outcomes of oral cancer patients: a retrospective cohort study

The contemporary literature is discordant regarding the role of delayed diagnosis in the prognosis of patients with oral cancer. This study examined data on a previously reported cohort of 101 patients with oral squamous cell carcinoma diagnosed at a single institution between 2008 and 2010. The time interval between symptom onset and initial histological diagnosis (diagnostic delay) was recorded for each patient, as were demographic data and cancer features such as T stage, nodal status, and smoking status. The mean follow-up period was 4 years 10 months. The mean diagnostic delay was 4 months, mean overall survival was 5 years 6 months, and mean disease-specific survival was 4 years 9 months. No significant correlation was found between diagnostic delay and overall survival, disease-specific survival, or recurrence rates. Patients with node-positive disease were more likely to be diagnosed earlier, whereas women and non-smokers were more likely to have a delayed diagnosis. Inherent tumour biology is likely an important prognostic factor separate to diagnostic delay. Public education efforts should focus on symptom recognition and encourage early presentation for investigation of oral lesions, particularly for females and non-smokers, so that more aggressive tumours can be treated sooner to give the best chance at survival.     

Clinicopathologic factors associated with malignant transformation of oral leukoplakias: a retrospective cohort study

It is clinically challenging to identify oral leukoplakias that have a high risk of undergoing malignant transformation. The aim of this retrospective study was to elucidate the associations between malignant transformation of oral leukoplakias and various clinicopathologic factors. Patients with a diagnosis of clinical oral leukoplakia, verified through histopathologic examination and with access to digital images of the lesion, were retrospectively included for the period 2003–2013. Using the clinical images, all lesions were re-evaluated regarding diagnosis and clinical subtype. Of the 234 included patients, with a median follow-up of 9 years, 27 (11.5%) developed oral squamous cell carcinoma. Among the clinicopathologic factors investigated, non-homogeneous oral leukoplakia (OL), OL with dysplasia, and OL localized to the tongue showed statistically significant increased rates of malignant transformation in the multivariate Cox regression analysis. Non-homogeneous OL showed a 15.2-times higher transformation rate than homogenous OL (P < 0.001). Dysplastic leukoplakias developed into carcinomas 2.4-times more often than did non-dysplastic leukoplakias (P = 0.048). OL located on the tongue showed a 2.8-times higher malignant transformation rate than OLs at other oral locations (P = 0.018), when other locations were combined into one group. Non-homogeneous OL, OL with dysplasia, and OL localized to the tongue have higher transformation rates.     

Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.     

异牡荆素对非小细胞性肺癌细胞自我更新和凋亡的影响

目的研究异牡荆素(ISO)对非小细胞性肺癌(NSCLC)细胞的影响和潜在的机制。方法将A549和H1650细胞分别分为空白组、低剂量实验组(4μmol·L^-1 ISO)和高剂量实验组(16μmol·L^-1 ISO)。用噻唑蓝法检测NSCLC细胞活性,用肿瘤球形成实验检测NSCLC细胞的细胞球形成率,用Western blot法检测NSCLC细胞凋亡、自我更新、无翅型MMTV整合位点家族/β-连环蛋白(Wnt/β-catenin)信号通路相关蛋白的表达水平。结果与空白组比较,低、高剂量实验组中A549和H1650细胞在24,48和72 h的细胞活性均显著降低。低、高剂量实验组和空白组中A549细胞的细胞球形成率分别为(4.18±0.45)%,(2.01±0.67)%和(6.02±0.57)%,切割的半胱氨酸蛋白酶-3相对表达量分别为0.24±0.08,1.25±0.13和0.06±0.07,SRY相关高迁移率族盒蛋白-2相对表达量分别为0.49±0.04,0.25±0.03和1.00±0.09,Kruppel样因子4相对表达量分别为0.68±0.04,0.44±0.03和1.01±0.06,Wnt1相对表达量分别为0.63±0.06,0.28±0.04和1.00±0.06,β-catenin相对表达量分别为0.41±0.05,0.22±0.03和1.01±0.09;与空白组比较,低、高剂量实验组中A549细胞的上述指标的差异均有统计学意义(P<0.05,P<0.01)。上述3组中H1650细胞的上述指标也呈现一致的现象。结论ISO可能通过抑制Wnt/β-catenin信号通路来抑制NSCLC细胞活性和自我更新,并促进其凋亡。