头颈部恶性肿瘤嗜神经侵袭临床诊治现状

嗜神经侵袭是肿瘤通过神经扩散与转移的一种独特的生物学行为,与复发、转移、预后密切相关。随着研究的不断深入,人们普遍认识到嗜神经侵袭的临床意义。但由于头颈部肿瘤发病率相对较低,不同解剖部位、不同病理类型嗜神经发生率各不相同,故缺乏高级别的循证医学证据。目前嗜神经侵袭的病理学机制尚未完全阐明,也无针对神经侵犯的特异性治疗手段,因此头颈部肿瘤嗜神经侵袭的治疗对于临床医师是一个巨大的挑战。本文就头颈部恶性肿瘤中嗜神经侵袭的临床诊治现状做一综述。     

Non-squamous cell carcinoma diseases of the larynx: clinical and imaging findings

IntroductionSquamous cell carcinoma is the most common laryngeal neoplasm and accounts for approximately 95% of all malignant neoplams of the larynx. However, various benign and malignant tumors and inflammatory diseases may affect the larynx.ObjectiveThe purpose of this study is to analyze the clinical and imaging findings of non-squamous cell neoplasms and inflammatory diseases of the larynx.MethodsThis retrospective study was conducted in 18 patients who were diagnosed with non-squamous cell carcinoma lesions of larynx at our institution between 2007-2017. Clinical symptoms, examination findings, imaging characteristics, histopathologic diagnosis and treatment modalities were analyzed.ResultsThere were 9 malignant lesions (2 chondrosarcoma, 1 neuroendocrine tumor-atipical carcinoid, 1 Natural Killer/T-cell lymphoma, 1 diffuse large B-cell lymphoma, 3 plasmocytoma-multiple myeloma involvement, 1 adenocarcinoma metastasis), 3 benign neoplasms (chondroma, paraganglioma, lipoma), 2 tumor-like lesions (Brown tumor and inflammatory myofibroblastic tumor), 3 inflammatory lesions (Wegener granulomatosis, Behçet's disease and tuberculosis involvements), and 1 vascular malformation. The most common presenting symptom was hoarseness (66.6%). Paraganglioma was seen as hypervascular lesion on computed tomography and magnetic resonance imaging and showed intense tracer uptake on 68Gallium-DOTA-peptide PET/CT. Chondroid matrix calcifications were detected in chondroma and chondrosarcoma-grade 1. In patients with vascular malformation and lipoma, the typical imaging findings made it possible to diagnose.ConclusionImaging studies may provide clues for diagnosis of non-squamous cell laryngeal lesions. Clinical and imaging findings and previous clinical history should be evaluated together in clinical management of laryngeal lesions.     

Medullary Thyroid Carcinoma Metastasis to the Breast and Axillary Lymph Nodes

Breast metastases of medullary thyroid carcinoma (MTC) are extremely rare, and only a few cases have been reported in the literature so far. Here, we report a case of metastatic MTC to the breast and axillary lymph nodes (LN). The case illustrates that (1) metastatic MTC of the breast could be clinically and pathologically misdiagnosed as primary breast cancer, such as invasive lobular carcinoma with axillary LN involvement; (2) unlike other metastatic breast cancer patients, who have very poor prognoses, our patient survived for more than 5 years after the breast and axillary surgery; and (3) metastasis of MTC to the breast is accompanied by axillary LN metastasis, which requires thorough axillary LN dissection, as in most primary breast cancers.     

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

影像学在神经内分泌肿瘤合并肝转移患者早期治疗评价中的作用:从解剖学到功能学

神经内分泌肿瘤病程中易发生肝转移。目前,神经内分泌肿瘤肝转移(NENLM)的治疗方法日益多样化,这使得过去单纯从形态学变化的角度评价其治疗效果具有一定的局限性。新兴的影像学生物标志物能够从功能层面描述肿瘤治疗相关的变化,为NENLM的疗效评价提供新的方法和思路。本文主要总结影像学评价NENLM早期疗效的现状及研究进展,旨在为有效评价NENLM的早期疗效提供参考,并为进一步探索与NENLM早期疗效相关的生物标志物提供思路。     

Myeloproliferative neoplasms

The myeloproliferative neoplasms (MPN) are a group of clonal myeloid proliferations characterised by varying combinations of increased circulating red cells, granulocytes and platelets caused by excess proliferation of haemopoietic precursors in bone marrow with retained cellular maturation. These disorders typically pursue an indolent course requiring management of the consequences of the increased circulating elements (predominantly effects of thrombosis of haemorrhage in different body organs). Patients have complex symptoms, including fatigue, which are not yet fully explained. The MPN carry varying risks of progression to an acute phase characterised by increasing bone marrow and circulating blasts cells, and/or to fibrosis characterised by falling peripheral cell counts and increasing splenomegaly. Megakaryocyte morphology in BMT samples provides essential clues for diagnosis and subtyping in MPN; high quality and consistent reticulin staining for accurate assessment is also key.