甲状腺未分化癌发生肺转移的危险因素分析

目的:探讨甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)发生肺转移的危险因素。方法:回顾性分析2010年至2015年SEER数据库中被确诊为ATC的405例患者临床病理资料。通过对年龄、种族、性别、原发灶最大径、原发灶数量、甲状腺外组织侵犯、食管侵犯、气管侵犯、中央区淋巴结转移、颈侧区淋巴结转移10个因素进行单因素分析,进而对单因素分析中有统计学差异的指标行多因素Logistic回归分析,寻找ATC患者发生肺转移的危险因素。结果:405例ATC患者中,发生肺转移107例,未发生肺转移298例。单因素分析显示:原发灶最大径>4 cm、甲状腺外组织侵犯、颈侧区淋巴结转移是预测发生肺转移的显著性因素(均P<0.05)。多因素Logistic回归分析显示:原发灶最大径>4 cm及颈侧区淋巴结转移是ATC患者发生肺转移的独立危险因素(均P<0.05)。结论:原发灶最大径>4 cm、颈侧区淋巴结转移的ATC患者极易发生肺转移,因此,一定要认真参考病理结果,若发现存在以上肺转移危险因素,则积极采取多模式治疗方案,并缩短随访时间,行相关检查(如胸部CT扫描、PET-CT等)。     

左、右半结肠癌肝转移患者射频消融治疗疗效及生存的对比分析

目的:探讨原发部位分别位于左、右半结肠的结肠癌肝转移患者行超声引导下肝转移瘤射频消融术后的生存差异及预后影响因素分析。方法:回顾性分析2010年1月至2015年12月于我科行射频消融治疗的结肠癌肝转移患者100例，其中左半结肠癌62例，右半结肠癌38例，分析原发部位不同的结肠癌肝转移患者在进行超声引导下射频消融治疗后的生存情况。结果:左半结肠癌肝转移患者射频消融术后1、3、5年总体生存率及中位生存期均高于右半结肠癌肝转移患者（88.71% vs 73.68%、62.90% vs 30.02%、49.72% vs 26.33%、55个月 vs 23个月），且二者生存曲线差异具有统计学意义（P＜0.05）。经Log-rank检验及COX多因素分析，左、右半结肠癌肝转移患者射频消融治疗术后的生存情况存在差异。此外，原发灶淋巴结转移情况、患者术前CA199水平及原发灶分化程度是患者射频消融治疗术后生存情况的影响因素。结论:左半结肠癌肝转移患者射频消融术后整体生存率明显高于右半结肠癌肝转移患者，左半结肠癌与右半结肠癌肝转移患者在射频消融治疗术后生存状况存在明显差异。     

Nationwide Real-world Cohort Study of First-line Tyrosine Kinase Inhibitor Treatment in Epidermal Growth Factor Receptor-mutated Non–small-cell Lung Cancer

BackgroundOnly a few randomized trials directly compared the relative efficacy of tyrosine kinase inhibitors (TKIs) in patients with advanced epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC), and most trials comprised selected series from Asian populations. Therefore, the aim of this study was to assess the overall survival (OS) of advanced EGFR-mutated NSCLC in a large white population and to evaluate variation between different TKIs and identify predictors of survival.Patients and MethodsInformation about clinical characteristics, treatment, and survival for 873 patients with stage IV EGFR + NSCLC, diagnosed from 2015 through 2017, was derived from the Netherlands Cancer Registry. OS was evaluated by actuarial analysis and multivariable Cox regression. Prognostic factors are reported as hazard ratios and 95% confidence intervals.ResultsA total of 596 (68%) patients received first-line treatment with regular TKIs, providing a median survival of 20.2 months. Forty-five percent of patients were 70 years and older, and 54% of patients had distant metastasis in multiple organs. In the multivariate analysis, survival was significantly worse for men, and patients with higher age, poorer performance, and ≥ 3 organs with metastasis. Compared with erlotinib, OS was worse for gefitinib users (adjusted hazard ratio, 1.30; 95% confidence interval, 1.02-1.64), predominantly in patients with brain metastasis.ConclusionDutch patients with EGFR-mutated NSCLC who received first-line treatment with regular TKIs have a median OS of 20.2 months in a nationwide real-world cohort. In patients with brain metastasis, erlotinib showed superior results compared with gefitinib and was similar to afatinib.     

虫类药治疗乳腺癌骨转移思路探析

虫类药因其药性的猛烈,药物功效对症,成为治疗乳腺癌骨转移的常用药。相较于其他中药,虫类药对各类恶性肿瘤有较好的疗效,但在运用的同时还需注意,虫类药的毒性以及其对脏腑,尤其是肝脏的损伤,需动态关注患者各项生命体征变化,药用时间不宜过长,应严格遵守药物禁忌、配伍等规则,并要求临床医师辨证准确,密切观察患者病情变化。同时,虫类药的更多药物作用机制、临床方案的优化等,需进一步研究探讨。     

The FABP12/PPARγ pathway promotes metastatic transformation by inducing epithelial‐to‐mesenchymal transition and lipid‐derived energy production in prostate cancer cells

Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid‐binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial‐to‐mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid β‐oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARγ activation which, in turn, regulates FABP12''s role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP‐PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.

Abbreviations

AR

androgen receptor

ATP

adenosine triphosphate

CN

copy number

CPT1

carnitine palmitoyltransferase I

CS

citrate synthase

EMT

epithelial–mesenchymal transition

ET

electron transfer‐state

FABP

fatty acid‐binding protein

LD

lipid droplet

OA

oleic acid

PCa

prostate cancer

PPAR

peroxisome proliferator‐activated receptor

PPRE

peroxisome proliferator‐activated receptor response element

TZD

thiazolidinediones

     

A Novel Algorithm to Differentiate Between Multiple Primary Lung Cancers and Intrapulmonary Metastasis in Multiple Lung Cancers With Multiple Pulmonary Sites of Involvement

IntroductionDifferentiating between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) is critical for developing a therapeutic strategy to treat multiple lung cancers with multiple pulmonary sites of involvement.MethodsWe retrospectively included 252 lesions (126 pairs) from 126 patients with surgically resected multiple lung adenocarcinomas. Each pair was classified as MPLC or IPM based on histopathologic findings as the reference standard. A novel algorithm was established with four sequential decision steps based on the combination of computed tomography (CT) lesion types (step 1), CT lesion morphology (step 2), difference of maximal standardized uptake values on positron-emission tomography/CT (step 3), and presence of N2/3 lymph node metastasis or distant metastasis (step 4). The diagnostic accuracy of the algorithm was analyzed. Performances of 11 observers were assessed without and with knowledge of algorithm.ResultsAmong 126 pairs, 90 (71.4%) were classified as MPLCs and 36 (28.6%) as IPMs. On applying the diagnostic algorithm, the overall accuracy for diagnosis of IPM among conclusive cases up to step 4 was 88.9%, and 65 and 44 pairs were correctly diagnosed based on step 1 and step 2, respectively. Specificity and positive predictive value for diagnosis of IPM increased significantly in all observers compared with reading rounds without the algorithm.ConclusionsApplication of the algorithm based on comprehensive information on clinical and imaging variables can allow differentiation between MPLCs and IPMs. When both of two suspected malignant lesions appear as solid predominant lesions without spiculation or air-bronchogram on CT, IPM should be considered.     

Proposal of a novel subclassification of pN3b for improvement the prognostic discrimination ability of gastric cancer patients

IntroductionIn the recent edition of TNM staging system, pN3b gastric cancer were separated into the staging system for better prognosis accuracy. The definition of pN3b contains a large range of metastasis lymph nodes (mLNs). However, few studies have evaluated the prognosis of pN3b patients and it remains unknown whether these patients were reasonably assigned into the same substage.Materials and methodsA total of 642 pN3b patients from a multi-institutional cohort in China were included. Disease-specific survival (DSS) was estimated using the Kaplan-Meier method and the Cox proportional hazards regression analysis was used to identify the independent prognostic factors. Restricted cubic spine model was used to specify the association between the continuous variables and the logarithm Hazard ratios (HRs). The optimal cut-off value of mLNs for DSS was identified using the X-tile software.ResultsThe 5-year DSS rate of total pN3b cohort was 15.4%. The smooth curves showed a non-linear association between the mLNs and the logarithm HRs. All pN3b gastric cancer patients were divided into two subclassifications (pN3b1: 16-24 mLNs, pN3b2: ≥25 mLNs). Significant survival difference was observed between two subclassifications (P = 0.048). Additionally, more LNs examined could decrease the death risk of pN3b patients and bring survival benefit only in pN3b1 patients, but not in pN3b2 patients.ConclusionsWe proposed a novel subclassification of pN3b patients, which assigned patients into two subclassifications with significant survival difference. Future study should explore the prognosis value based on this novel subclassification in TNM staging system.     

The prognostic value of lymph node ratio in Medullary thyroid carcinoma: A multi-center study

IntroductionThe lymph node ratio (LNR), which represents the proportion of metastatic lymph nodes resected, has been found to be a prognostic variable in several cancers, but data for Medullary thyroid carcinoma (MTC) are sparse. The aim of this study was to determine the value of the LNR in predicting outcome in patients with MTC.Materials and methodsA retrospective multicenter study design of 107 patients with MTC who underwent total thyroidectomy with neck dissection between 1984 and 2016. The association of LNR with patient and tumor characteristics and prognostic factors was evaluated.ResultsStudy population consisted of 53.3% female, mean age at diagnosis was 50.3 ± 18.4 years; 16.8% had inherited MTC. LNR was positively correlated with tumor size (p = 0.018) and inversely correlated with age at diagnosis (p = 0.024). A higher LNR was associated with extrathyroidal extension (p < 0.001), multifocality (p = 0.001), bilateral tumor (p = 0.002), distant metastases (p < 0.001), and tumor recurrence (OR = 14.7, p < 0.001). LNR was also correlated to postoperative calcitonin levels (p < 0.001) and carcinoembryonic antigen (p = 0.011). LNR >0.1 was associated with shorter disease-specific survival in patients at risk: tumor larger than 20 mm at diagnosis (p = 0.013), sporadic MTC (p = 0.01), and age above 40 years at diagnosis (p = 0.004). Cox multivariate survival analysis revealed LNR as the only significant independent factor for disease free survival (p = 0.005).ConclusionsThis study showed that LNR correlates well with patient and tumor characteristics and prognostic variables. We suggest that LNR should be considered an important parameter for predicting outcome in MTC.