Lapatinib: a dual inhibitor of EGFR and HER2 tyrosine kinase activity

Lapatinib (GW 572016) is an oral inhibitor of the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2), which are both frequently altered in human malignant tumors. Being a multitargeting agent, it has the theoretical ability to provide more efficient antitumor activity and delay the onset of tumor resistance. Based on promising preclinical results, lapatinib is being extensively studied in cancer patients. In Phase I clinical trials, the side effect profile of lapatinib results are favorable, with a few patients experiencing serious toxicity. Phase II studies showed that lapatinib has meaningful clinical activity in the setting of HER2-positive advanced breast cancer patients. Unfortunately, its activity in epidermal growth factor receptor-dominated cancers, such as colorectal cancer or squamous cell carcinoma of the head and neck, is modest. An extensive program is now ongoing in breast cancer patients to establish the correct role of lapatinib in this clinical setting. Studies in breast cancer, as well as in other solid tumors are also collecting a large amount of biological data. Correlative studies will hopefully clarify predictive factors of lapatinib efficacy that can be applied in clinical practice in order to select patients for treatment.     

Arterial therapies of non-colorectal cancer metastases to the liver (from chemoembolization to radioembolization)

Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization (TACE) represents an essential component of interventional oncology known for many years and performed by many interventional radiologists first in primary liver tumors and nowadays even in metastases of different origins. Radioembolization (RE) has been introduced to the clinical arsenal of cytoreductive modalities in recent years. There is growing evidence for efficiency in liver tumors of various entities, with the most prominent ones being hepatocellular carcinoma, colorectal cancer, and neuroendocrine tumors. Hepatic metastases of other tumor entities (breast cancer, malignant melanoma, and pancreatic cancer) are treatment-sensitive. This article focuses on procedural and technical aspects for selection, preparation, and performance of treatment as well as the results in metastatic breast cancer, neuroendocrine tumors, melanoma, and pancreatic cancer giving an overview of the results after RE, transarterial embolization, or TACE.     

高强度聚焦超声体外治疗恶性实体肿瘤的临床安全性研究

目的：研究高强度聚焦超声（HIFU）体外治疗恶性实体肿瘤的临床安全性。方法：HIFU体外治疗恶性实体肿瘤患者164例,观察治疗过程中,治疗后的全身和局部的变化。结果：治疗中,治疗后患者生命体征稳定,主要器官功能基本正常;局部瘤灶无破裂或出血,无黄疸或胆汁漏溢,未发现瘤灶邻近脏器或血管损伤,结论：HIFU体外治疗恶性实体肿瘤是安全的。     

病灶周围红晕在乳腺实性肿瘤超声弹性成像诊断中的价值探讨

目的探讨病灶周围红晕在乳腺实性肿瘤超声弹性成像诊断中的价值。 方法对264例患者共281个乳腺实性肿瘤进行超声弹性成像检查。以手术病理为诊断金标准，分析良恶性乳腺实性肿瘤剧围红晕特征。 结果超声弹性成像中病灶周围红晕宽度及其分布特征在乳腺癌和纤维腺瘤两组病例中差异无统计学意义（P＞0．05）。 结论乳腺实性肿瘤周罔红晕表现无助于病灶良恶性鉴别。     

Image-based control of the magnetic resonance imaging-guided focused ultrasound thermotherapy

Magnetic resonance imaging (MRI)-guided focused ultrasound surgery (FUS) is a full noninvasive approach for localized thermal ablation of deep tissues, coupling the following: (1) a versatile, nonionizing physical agent for therapy and (2) a state-of-the art diagnosis and on-line monitoring tool. A commercially available, Food and Drug Administration-approved device using the MRI-guided FUS exists since 2004 for the ablation of benign tumors (uterine fibroids); however, the ultimate goal of the technological, methodological, and medical research in this field is to provide a clinical-routine tool for fighting localized cancer. When addressing cancer applications, the accurate spatial control of the delivered thermal dose is mandatory. Contiguous destruction of the target volume must be achieved in a minimum time, whereas sparing as much as possible the neighboring healthy tissues and especially when some adjacent regions are critical. This paper reviews some significant developments reported in the literature related to the image-based control of the FUS therapy for kidney, breast, prostate, and brain, including the own experience of the authors on the active feedback control of the temperature during FUS ablation. In addition, preliminary results of an original study of MRI-guided FUS ablation of VX2 carcinoma in kidney, under active temperature control, are described here.     

超声和MRI影像学及影像组学在乳腺癌中的研究进展

乳腺癌是全球女性最常见的恶性肿瘤之一,发病率和致死率居癌症首位,早期诊断和早期治疗可以提高疾病预后效果,降低疾病相关死亡率。超声和MRI影像学是乳腺癌诊疗指南推荐对原发肿瘤评估无创检查方式,随着科技的发展,越来越多的影像学新技术应用于临床实践,乳腺癌检出率和诊断准确率都有了很大提高。人工智能的出现,拓展了影像组学的应用,推动了乳腺癌精准医疗的发展。本文针对超声和MRI影像学及影像组学在乳腺癌临床诊疗中的应用进展进行了综述。     

血清IL-1β、IL-10、IFN-γ在乳腺肿瘤定性诊断中价值及与预后相关性研究

目的探讨血清白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、干扰素-γ(IFN-γ)在乳腺肿瘤定性诊断中价值及与预后相关性。方法选取2016年9月至2018年11月本院92例乳腺癌患者为乳腺癌组,同期行手术切除治疗的92例乳腺良性肿瘤(乳腺纤维瘤)患者为良性组。对比2组与不同临床特征乳腺癌患者血清IL-1β、IL-10、IFN-γ水平,绘制受试者工作特征(ROC)曲线分析血清各指标单一与联合检测对乳腺肿瘤良恶性的诊断价值,并比较不同预后(1年复发、未复发)乳腺癌患者血清各指标表达,Spearman相关性分析探讨血清各指标表达与乳腺癌预后复发的关联性。结果乳腺癌组血清IL-1β、IL-10、IFN-γ水平高于良性组(P<0.05);血清IL-1β、IL-10、IFN-γ诊断乳腺肿瘤良恶性均具有较高AUC,应用3者联合诊断乳腺肿瘤良恶性的敏感度为77.17%、特异度为84.78%;临床分期为Ⅲ~Ⅳ期、组织分化程度为中低分化、有淋巴结转移乳腺癌患者血清IL-1β、IL-10、IFN-γ水平高于临床分期为Ⅰ~Ⅱ期、组织分化程度为高分化、无淋巴结转移患者(P<0.05);1年复发患者血清IL-1β、IL-10、IFN-γ水平高于未复发者,差异有统计学意义(P<0.05);Spearman相关性分析显示,血清IL-1β、IL-10、IFN-γ表达与乳腺癌预后复发呈显著正相关。结论血清IL-1β、IL-10、IFN-γ在乳腺肿瘤定性诊断中具有重要价值,与乳腺癌临床分期、组织分化程度、淋巴结转移密切相关,且可用于预后复发预测。     

乳腺肿瘤常规超声联合超声造影影像组学特征与乳腺癌分子分型相关性的研究进展

影像组学（radiomics）是一种从医学影像中高通量地提取影像特征来深入挖掘内部数据信息的技术方法,通过肿瘤分割、特征提取与模型建立来辅助临床对肿瘤的诊断与治疗。在精准医疗时代,乳腺癌（breast cancer,BC）的个体化早期诊治尤为重要。常规超声是诊断乳腺肿瘤的重要影像学方法,超声造影（contrast enhanced ultrasound,CEUS）可以实时显示乳腺肿瘤微血管灌注的形态学及功能学变化,在此基础上产生的超声及超声造影影像组学在乳腺肿瘤良恶性诊断及判断乳腺癌分子分型中具有潜在临床应用价值。本文就乳腺肿瘤常规超声联合超声造影影像组学特征与乳腺癌分子分型相关性方面进行综述。     

实时三维超声在乳腺癌诊断中的研究与进展

近几年,乳腺癌的发病率呈逐年上升趋势,已成为女性最常见的恶性肿瘤之一,早期正确诊断对临床治疗及预后具有重要意义。随着影像技术的不断发展,三维超声成像已成为诊断乳腺癌的重要方法。本文就乳腺三维超声成像技术的研究现状做一综述,并对其未来发展进行展望。     

乳腺癌影像组学研究进展

乳腺癌是我国女性最常见的恶性肿瘤,如何更好地对其进行早期诊断、治疗和预后评估是临床亟待解决的问题。影像组学以非侵入性方式高通量提取并分析病灶的图像特征,可提供更多潜在的肿瘤信息,进而指导临床进行精准诊疗。近年来,影像组学在乳腺癌领域的研究被广泛关注,涉及乳腺癌患者全程管理的各个环节,诊断方面研究已趋于成熟,逐步进入临床转化阶段,疗效评估和预后预测尽管尚处于初步探索阶段,但具有广阔的发展前景。本文从诊断、疗效评估和预后预测三个方面进行综述,以期为临床诊疗提供借鉴。     

Color Doppler flow as an indicator of nodal metastasis in solid breast masses.

Tumor metastases are dependent on angiogenesis. This prospective study evaluates the role of color Doppler sonographic signals in (1) detecting blood flow in solid breast masses, (2) differentiating between benign and malignant breast tumors, and (3) identifying women at risk for axillary lymph node metastasis. Ultrasonographically proved solid breast masses from 95 women were evaluated with color Doppler imaging for the presence of blood flow. A characteristic curvilinear or branching signal pattern, labeled the "rim sign," was noted to be either present or absent at the periphery of the mass in all cases. The color Doppler sonographic signals in 86 patients with pathologic results were correlated with the occurrence of malignancy and axillary lymph node metastasis. Fifty-three of the 86 patients (62%) had benign breast disease and 33 patients (38%) had malignant tumors. Sixteen (30%) of the benign tumors and 20 (61%) of the malignant cancers demonstrated a positive rim sign. A positive rim sign has a 61% sensitivity and a 70% specificity for the prediction of breast malignancy. In the malignant masses, nodal involvement occurred in 50% of patients with a positive rim sign and 10% of patients with a negative rim sign. A negative rim sign has a negative predictive value of 90% for nodal metastasis. Color Doppler imaging can detect blood flow in both malignant and benign solid breast masses. A positive rim sign is a poor prognostic factor whereas a negative rim sign is a good prognostic indicator for axillary nodal metastases.     

超声新技术提升乳腺影像报告和数据系统分类特异度应用进展

乳腺影像报告和数据系统（BI-RADS）建议对4a类及以上的肿物予病理学检查,但活检恶性率偏低,提升BI-RADS的特异度是亟待解决的问题。作为我国最常见的乳腺影像学检查方法之一,超声诊断结果对临床决策至关重要。本文对近年来超微血管成像、全自动乳腺容积扫描、弹性成像、超声造影和人工智能技术辅助超声BI-RADS精准分类的研究进展进行综述。     

MR imaging-controlled focused ultrasound ablation: a noninvasive image-guided surgery

The history of MR-guided FUS demonstrates the need for merging advanced therapy technology with advanced imaging. Without the ability of MR imaging to localize the tumor margins and without the temperature-sensitive imaging that provides the closed-loop control of energy deposition, this method is inadequate for most clinical applications. Given these limitations,high-intensity focused ultrasound initially appeared to have a narrow application area and was not able to compete with other surgical or ablation methods. Today, MR imaging-guided FUS has become a safe and effective means of performing probe-delivered thermal ablations and minimally invasive surgery. Moreover, it has the potential to replace treatments that use ionizing radiation such as radiosurgery and brachytherapy. Although the cost of integrating"big ticket" MR imaging systems with complex and expensive phased arrays is high, this expenditure will largely be offset by eliminating hospitalization and anesthesia and by reducing complications. In effect, an investment in this emerging technology will ultimately redound to the benefit of the health care delivery system and, most important, to the patient. The FUS system provides a safe, repeatable treatment approach for benign tumors (eg, uterine fibroid and breast fibroadenoma) that do not require an aggressive approach. MR-guided FUS can also be used for debulking cancerous tissue. It has already been tested as a breast cancer treatment; its application for other malignancies in the brain, liver, and prostate is under development. MR-guided FUS offers an attractive alternative to conventional surgery because it incorporates intraoperative MR imaging, which provides far more precise target definition than is possible with the surgeon's direct visualization of the lesion. MR-guided FUS is undeniably the most promising interventional MR imaging method in the field of image-guided therapy today. It is applicable not only in the thermal coagulative treatment of tumors but also in several other medical situations for which invasive surgery or radiation may not be treatment options. The use of FUS for treating vascular malformation or functional disorders of the brain is also exciting. It is uniquely applicable for image-guided therapy using targeted drug delivery methods and gene therapy. Further advances in this technology will no doubt improve energy deposition and reduce treatment times. In the near future, FUS will offer a viable alternative to conventional surgery and radiation therapy; in the longer-term, it may also enable a host of targeted treatment methods aimed at eradicating or arresting heretofore intractable diseases such as certain brain malignancies and forms of epilepsy.     

Extracorporeal high intensity focused ultrasound in the treatment of patients with solid malignancy.

The ideal treatment of localized cancer should cause the complete death of tumor cells without damage to surrounding normal tissue. High intensity focused ultrasound (HIFU) is such a potential treatment, which can induce complete coagulation necrosis of a targeted tumor, at depth, through the intact skin. The concept of using HIFU as a non-invasive therapy has attracted attention in medicine for 60 years. Recently, it has received increasing interest as a promising modality for the treatment of localized solid malignancies. The goal of this article is to introduce recent clinical developments in the use of extracorporeal HIFU ablation for solid tumors, including those of liver, breast, bone, kidney, pancreas, soft tissue, and uterus. It describes the physical principles and ablative mechanisms, three-dimensional therapeutic regimes, and medical imaging used in HIFU. Currently, large numbers of patients with solid malignancy are already treated using HIFU, and short-term clinical results are very encouraging. However, large-scale randomized clinical trials are necessary to evaluate long-term efficacy of HIFU treatment for solid malignancies. It is concluded that this non-invasive ablation can be considered as a conventional therapy for widespread clinical use only when the results from prospective, randomized clinical trials worldwide are available.     

多参数皮下组织超声检查鉴别乳腺良恶性肿瘤的诊断分析

目的:分析多参数皮下组织超声检查在乳腺良恶性肿瘤鉴别诊断中的应用价值.方法:挑选2019年5月—2020年5月在我院收治的160例乳腺肿块患者,经超声检查获取二维形态、血流Adler分级等超声参数及超声弹性成像,分析比较面积比法、应变率方法和Itoh法在诊断乳腺肿瘤良恶性方面的应用价值,并且以病理诊断结果作为金标准,分...     

乳腺癌患者外周血血小板参数变化规律分析概况

乳腺癌是女性最常见的恶性肿瘤之一,研究发现血小板功能和状态与乳腺癌发生发展的关系密切,在乳腺癌的血行转移中起重要作用。本文分析总结乳腺癌患者外周血血小板计数(PLT)、血小板压积(PCT)、血小板分布宽度(PDW)、平均血小板体积(MPV)及血小板与淋巴细胞比值(PLR)变化规律,以期为乳腺癌的血行转移提供诊断依据和防治参考。     

Image retrieval with principal component analysis for breast cancer diagnosis on various ultrasonic systems.

OBJECTIVES: We present a computer-aided diagnostic (CAD) system with textural features and image retrieval strategies for classifying benign and malignant breast tumors on various ultrasonic systems. Effective applications of CAD have used different types of texture analysis. Nevertheless, most approaches performed in a specific ultrasonic machine do not indicate whether the technique functions satisfactorily for other ultrasonic systems. This study evaluated a series of pathologically proven breast tumors using various ultrasonic systems. METHODS: Altogether, 600 ultrasound images of solid breast nodules comprising 230 malignant and 370 benign tumors were investigated. All ultrasound images were acquired from four diverse ultrasonic systems. The suspicious tumor area in the ultrasound image was manually chosen as the region-of-interest (ROI) subimage. Textural features extracted from the ROI subimage are supported in classifying the breast tumor as benign or malignant. However, the textural feature always behaves as a high-dimensional vector. In practice, high-dimensional vectors are unsatisfactory at differentiating breast tumors. This study applied the principal component analysis (PCA) to project the original textural features into a lower dimensional principal vector that summarized the original textural information. The image retrieval techniques were employed to differentiate breast tumors, according to the similarities of the principal vectors. The query ROI subimages were identified as malignant or benign tumors according to characteristics of retrieved images from the ultrasound image database. RESULTS: Using the proposed CAD system, historical cases could be directly added into the database without a retraining program. The area under the receiver-operating characteristics curve for the system was 0.970+/-0.006. CONCLUSION: The CAD system identified solid breast nodules with comparatively high accuracy in the different ultrasound systems investigated.     

乳腺癌多普勒超声诊断进展

乳腺癌是女性最为常见的恶性肿瘤之一,早期准确诊断具有重要意义。彩色多普勒及能量多普勒超声是诊断乳腺癌的重要方法。本文就其二者在乳腺癌诊断中的应用综述如下。     

A comprehensive clinicopathological evaluation of the differential expression of microRNA-331 in breast tumors and its diagnostic significance

ObjectiveMicroRNA-331 (miR-331) has shown regulatory activity against several genes whose expression has been claimed to be deregulated in breast tumors, including that of epidermal growth factor receptor 2 (HER2). Herein, the clinical value of miR-331 expression was investigated by analyzing its levels in breast benign and malignant tumors.MethodsThe expression levels of miR-331 were quantified via real-time PCR in 130 malignant and 66 benign breast tissue specimens collected after surgical resection of primary tumors. The generated data were analyzed by applying several statistical tests in order to examine the relationship of miR-331 expression with various established clinicopathological features and survival data of patients.ResultsOur data showed that miR-331 was overexpressed in malignant breast tumors compared to their benign counterparts both overall (P = 0.026) and individually when the subgroups of fibroadenoma and invasive ductal carcinoma were analyzed with each other (P = 0.001). ROC curve analysis confirmed the diagnostic value of these variations, providing an AUC value equal to 0.597 (P = 0.026) and 0.663 (P = 0.001), respectively. Furthermore, miR-331 levels were elevated (P = 0.026) in ductal cancerous specimens compared to the lobular ones but failed to correlate with other clinicopathological features or survival data of the breast cancer patients.ConclusionsOur results provide evidence that miR-331 levels might provide valuable information regarding the differential diagnosis of benign and malignant breast tumors but present no prognostic value for breast cancer.     

Glutathione and its metabolizing enzymes in patients with different benign and malignant diseases

Objectives: Evaluation of glutathione (GSH) system in different tumors to reveal its potential usefulness in a clinical setting.

Design and methods: In addition to 10 normal controls, blood and tissue samples (85 benign and 109 malignant) from patients with breast, ovarian, prostatic, and liver neoplasms were investigated. The GSH concentration, glutathione S-transferase, glutathione peroxidase, and glutathione reductase activities were biochemically measured.

Results: Whereas all the components of the GSH system increased in patients with breast tumors, few components were significantly changed in patients with malignant ovarian, prostatic as well as metastatic liver diseases. GSH had the highest Z scores in ovarian and breast tumors. It was correlated (p < 0.05) with both glutathione S-transferase, glutathione peroxidase in breast cancer and with glutathione S-transferase only in prostate cancer. No correlation could be found in the expression of the GSH system in the blood and tissues of the same group of patients.

Conclusion: This work revealed that measurement of some and/or all components of the GSH system might be of clinical value in some malignant cases.