肿瘤标志物在肺癌脑膜转移辅助诊断中的应用

目的: 探讨癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)和细胞角蛋白片断抗原(CYFRA21-1)3种肿瘤标志物血清及脑脊液中含量在肺癌脑膜转移辅助诊断中的应用价值,并选择最理想的脑脊液肿瘤标志物组合。 方法: 采用RocheE170全自动免疫分析仪检测35例肺癌脑膜转移患者、35例脑部良性肿瘤患者血清和脑脊液中3种肿瘤标志物的含量。脑膜转移患者根据神经系统检查、脑脊液细胞学和核磁共振检查确诊。 结果: 肺癌脑膜转移患者的血清和脑脊液中3种肿瘤标志物水平均明显高于脑良性肿瘤组,差异有统计学意义(P<0.01);脑膜转移患者脑脊液中肿瘤标志物水平高于血清,差异有统计学意义(P<0.01)。按照实验室标准值确定血清肿瘤标志物阳性标准,CEA>5μg/L,NSE>15.2μg/L,CYFRA21-1>3.3μg/L。根据受试者工作曲线确定满足正确诊断指数最大值的临界点为脑脊液检测阳性判定标准,CEA>4.7μg/L,NSE>14.6μg/L,CYFRA21-1>5.5μg/L,CEA,NSE和CYFRA21-1的敏感性和特异性分别为91.4%,91.4%;51.4%,94.3%和82.9%,97.1%。脑脊液肿瘤标志物的联合检测组合中,三项指标任意1项阳性的诊断敏感性100%,三项指标同时阳性的诊断特异性100%。 结论: 脑脊液中3种肿瘤标志物水平对于肺癌脑膜转移的诊断,尤其对于那些细胞学和核磁共振检查难以确诊的患者,具有重要的临床意义,联合检测为最佳组合。     

厄洛替尼治疗脑脊液检测EGFR敏感突变的肺腺癌一例

背景与目的 脑是非小细胞肺癌(non-small cell lung cancer,NSCLC)常见的转移部位.有研究显示表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKI)可透过血脑屏障,发挥抗肿瘤作用.本例报道采用突变扩增阻滞系统(amplification refractory mutation system,ARMS)检测脑脊液EGFR突变指导临床治疗的可行性,并分析TKI治疗肺癌脑转移的疗效和安全性.方法 腰穿取得脑脊液标本,检测颅内压力,检验常规、生化及肿瘤标志物,查找脱落细胞,采用ARMS法检测EGFR基因突变,得到阳性结果后给予盐酸厄洛替尼(erlotinib,tarceva,特罗凯)治疗,150 mg,每天1次.按照实体瘤疗效评价标准1.1版(Response Evaluation Criteriation in Solid Tumours,RECIST v1.1)评价客观疗效,按照不良反应通用术语标准4.0版(Common Terminology Criteria for Adverse Events v4.0,CTC AE v4.0)评估用药期间发生的不良事件.结果 该患者多线治疗后,颅内病灶控制欠佳,脑脊液中发现异型细胞,EGFR基因19外显子缺失突变,服用厄洛替尼4周后,颅内客观疗效为部分缓解(partial response,PR),颅外客观疗效为疾病稳定(stable disease,SD),颅内无进展生存期(progression-free survival,PFS)10.5个月,总生存期(overall survival,OS)11个月.主要不良反应为皮疹(1级).结论 脑脊液检测EGFR突变可为制定治疗策略提供理论支持,根据不同的突变状态给予小分子靶向药物联合化疗,可分别控制颅内及颅外病灶.     

肺腺癌心脏转移1例报道

肺癌是心脏恶性转移瘤中最常见的原发肿瘤，临床上心脏作为肿瘤的靶器官容易被忽略。我科最近收治1例肺腺癌心脏转移患者，报道如下。 1临床资料     

STRN-ALK Fusion in Lung Adenocarcinoma with Brain Metastasis Responded Well to Ensartinib: A Case Report

STRN-ALK fusion is a rare ALK rearrangement identified in non-small cell lung cancer (NSCLC) patients. Here, we reported a case of lung adenocarcinomas with brain metastasis, harboring STRN-ALK fusion, responded well to ensartinib. This case report could provide more information for the therapeutic strategy selecting of NSCLC patients harboring STRN-ALK fusion.     

EGFR-Mutated Breast Metastasis of Lung Adenocarcinoma: A Case Report

Breast metastasis from other primary carcinoma is very rare and could be difficult to identify despite immunohistochemistry analysis. Breast metastasis from lung adenocarcinoma can mimic triple-negative breast cancer. Given the prognosis and therapeutic challenges, a correct diagnosis appears essential, and molecular biomarkers could be useful. We report the case of a 52-year-old woman with a breast mass initially diagnosed as primary breast cancer and secondarily attached to breast metastasis from an EGFR-mutated lung adenocarcinoma. The same activating EGFR mutations were identified in both the primary lung carcinoma and the breast metastasis.Key Words: Lung adenocarcinoma, Breast metastasis, EGFR mutation, Triple-negative breast cancer, EGFR tyrosine kinase inhibitors     

Complex Differential Diagnosis between Primary Breast Cancer and Breast Metastasis from EGFR-Mutated Lung Adenocarcinoma: Case Report and Literature Review

We present a case of a woman with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma who received gefitinib for 2 years and obtained a partial response. The patient then developed liver metastasis and a breast lesion, displaying high estrogen receptor (ER) expression and harboring the same EGFR mutation. From the radiological studies, it was not possible to make a differential diagnosis between primary breast cancer and breast metastasis from lung cancer. After the removal of the breast nodule, thanks to the clinical history, radiology, and above all, molecular and immunohistochemical investigations, a diagnosis of breast metastasis from lung adenocarcinoma was made. This case emphasizes the importance of a comprehensive clinical, pathological, and molecular analysis in the differential diagnosis between primary breast cancer and metastases from extramammary tumor to guide adequate treatment decision making.     

Cerebrospinal Fluid Concentrations of Gefitinib in Patients With Lung Adenocarcinoma

BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have high response and disease control rates in patients with central nervous system (CNS) metastases. However there have been only a few case reports on the penetration of gefitinib into the cerebrospinal fluid (CSF). The aim of this study was to investigate the CSF concentration of gefitinib in Chinese patients with lung adenocarcinomas.MethodsFrom March 2007 to December 2010, 22 patients were sequentially enrolled in this study at Peking Union Medical College Hospital (PUMCH). CSF and plasma samples were collected at the same time from each patient after at least 7 doses of gefitinib. The concentrations of gefitinib in the CSF and plasma were measured by high performance liquid chromatography coupled with tandem mass spectrometry. The clinical factors that may affect gefitinib penetration were analyzed.ResultsThe mean plasma and CSF concentrations of gefitinib were 491.8 ± 184.2 ng/mL and 6.2 ± 4.6 ng/mL, respectively, and the mean ratio of CSF-plasma concentration was 1.3% ± 0.7%. There was a good correlation between CSF and plasma gefitinib concentrations (R = 0.556, P = .006). The presence of CNS metastases was associated with increased gefitinib CSF penetration (1.46% vs. 0.95%; P = .042).ConclusionsThe concentration of gefitinib in CSF was low, and it was significantly related to the plasma gefitinib concentration. Because of the inadequate CNS drug exposure, patients in whom the extracranial lesions were well controlled may benefit from increasing gefitinib dose for the new intracranial lesions.     

Adenocarcinoma of the Lung with Selective Metastasis to the Lung: Clinical, Histologic and DNA-Cytofluorometric Analyses

In order to examine selective lung metastasis in lung adenocarcinoma, 7 patients who had died due to metastasis exclusively to the lung were analyzed. Because all of the tumors had been well differentiated adenocarcinoma, 21 cases of well differentiated adenocarcinoma which had metastasized to both the lung and other distant organs were selected as controls. Histologically, 6 of the 7 study cases were bronchiolo-alveolar carcinoma (BAC) of variable cytological type or papillary adenocarcinoma with a thin fibrovascular stroma without apparent destruction of the alveolar wall. There was no difference in clinical findings or nuclear DNA content (NDC) between the BAC and papillary adenocarcinoma with thin fibrovascular stroma. The fibrovascular stroma in the study cases was significantly thinner than that in the control cases ( P <0.01). Cytofluorometrically, the study cases had a significantly lower and less abnormal NDC than the control cases in terms of the mean NDC and DNA histogram patterns ( P <0.01 and P <0.05, respectively). On the basis of these findings, we conclude that 1) BAC can be classified within the same spectrum as well differentiated papillary adenocarcinoma, and 2) selective lung metastasis occurs in well differentiated adenocarcinomas showing mild NDC abnormalities and having a thin fibrovascular stroma without apparent destruction of the alveolar wall.     

原发性肺癌胃肠道转移2例报道并文献复习

原发性肺癌最常见的远处转移部位包括肺、肝、脑、骨、肾上腺等,胃肠道转移鲜有报道。北京大学肿瘤学院胸部肿瘤内科近期先后收治了经病理证实为原发性肺癌发生胃肠道转移的2例患者,本文将就其诊治及随访情况进行报告,并回顾国内外相关文献,以加深对肺癌少见部位转移的认识,避免漏诊和误诊。     

循环肿瘤细胞数量变化在预测局限性肾癌术后复发转移中的作用CSCD

目的探讨局限性肾癌患者行部分切除术后循环肿瘤细胞数量的变化在预测肿瘤复发转移中的作用。方法收集41例局限性肾癌患者,依据术前及术后3月循环肿瘤细胞数量变化分为阳性组(n=23)和阴性组(n=18)。对两组患者进行随访,终点事件为肿瘤复发转移。对所得数据进行统计学分析。结果阳性组复发转移率为43.5%,明显高于阴性组11.1%,差异有统计学意义(P=0.024);阳性组5年生存率为58.0%,阴性组为88.9%,差异有统计学意义(P=0.048)。结论术后3月循环肿瘤细胞计数较术前增加的局限性肾癌患者易出现复发转移。循环肿瘤细胞数量变化可作为较好的术后监测指标。     

Meningeal Rosai-Dorfman disease: report of three cases and literature review

Rosai-Dorfman disease is a well-recognized clinicopathological entity, which in rare cases affects the central nervous system, where it mimics meningioma. We describe three cases and review the literature. Histological and immunohistochemical confirmation is essential for definitive diagnosis. In addition to emperipolesis (lymphophagocytosis), reactivity for S-100 and CD68 and nonreactivity for CD-1a immunostaining are characteristic features of this histioproliferative disease. In contrast to meningioma, this tumor usually occurs in young males and infiltrates the brain parenchyma.     

Circulating Tumor Cells are Associated with Bone Metastasis of Lung Cancer

Lung cancer (LC) is the leading cause of cancer mortality worldwide, predominantly due to the difficulty of early diagnosis and its high metastatic potential. Recently, increasing evidence suggests that circulating tumour cells (CTCs) are responsible for cancer metastatic relapse, and CTCs have attracted interest in cancer metastasis detection and quantification. In present study, we collected blood samples from 67 patients with bone metastasis, and 30 patients without such metastasis, and searched for CTCs. Then the association of CTC numbers with bone metastasis and other clinico-pothological variants was analyzed. Results demonstrated that when 5 or 1 was taken as a threshhold for the CTC number, there were significantly higher positivity of CTCs in the bonemetastasis group than in the non-metastasis group. While the increase in CTC number was not significantly associated with any other clinicopathological factor, including age, gender, pathological type, intrapulmonary metastasis and lymph node metastasis, the CTC number in patients with positivity of the last above mentioned variants was obviously higher than in patients with negativity of the two variants. Taken together, the CTC number appears to be significantly associated with the bone metastasis from lung cancer.     

Meningeal carcinomatosis in patients with Breast Cancer: Report of 8 patients

BACKGROUND: Meningeal carcinomatosis (MC) is an uncommon but aggressive complication of advanced breast cancer with a recently increasing incidence. Although the prognosis is extremely poor for MC patients, early diagnosis and appropriate treatment are important. SUBJECTS AND METHODS: We reviewed 8 cases of MC from breast cancer at Kyoto University Hospital from 1990 to 1999. The median age was 51.5 years. All patients had widespread systemic metastases when diagnosed with MC. clinical symptoms were categorized into 3 groups: cranial nerve symptoms, spinal nerve symptoms, and other symptoms. Imaging studies were positive for MC in only 4 patients. Initial CSF cytology studies were positive in 4 patients, and repeated CSF cytology yielded positive results in the remaining 4 patients. Thus the median interval between the onset of any clinical symptom of MC and the initiation of treatment was 22.5 days (range 7 to 120 days ). All patients received whole brain radiotherapy (WBRT). Four patients were given intrathecal chemotherapy and/or intrathecal immunotherapy in addition to WBRT. RESULTS: Improvement of cranial nerve symptoms, spinal nerve symptoms, and other symptoms were observed in 3/5, 1/3, and 5/7 patients, respectively. Patients with cranial nerve symptoms who started WBRT within 29 days of the onset of the symptoms showed at least partial recovery whereas patients who started WBRT later showed no recovery. The median survival was 123 days (53 to 310 days). MC was the direct cause of death in 1 of 8 patients. CONCLUSION: When MC is clinically suspected, neither a negative imaging study nor a single negative CSF cytology can rule out MC. Prompt initiation of WBRT with or without intrathecal chemotherapy may be important for recovery from cranial nerve symptoms.     

低分化肺腺癌左上臂及背部肌内转移1例

肺癌晚期可出现各个不同脏器的转移而引起相应的症状,常常给患者带来极大的痛苦,甚至威胁到生命。肺癌转移主要以直接蔓延和淋巴结转移为主,晚期可发生血行转移。首发症状为软组织转移较少见,现对新疆医科大学第一附属医院诊治的1例低分化肺腺癌左上臂及背部肌内转移的病例报道如下。     

Skull Metastasis from Ampulla of Vater Adenocarcinoma: Case Report

We report a rare case of skull metastasis from ampulla of Vater adenocarcinoma in a patient with controlled primary neoplasm. This 65-year-old Korean man presented with headache and painful parietal scalp swelling, but he did not show any neurological deficits. Computed tomography revealed an osteolytic mass that invaded and expanded through the skull tables in full-thickness. On magnetic resonance images following Gadolinium injection, the mass appeared slightly hypointense signal on all sequences and intense heterogeneous enhancement. He underwent surgical excision with artificial grafting of calvaria and dura. Postoperative radiation therapy was ensued for metastatic adenocarcinoma, and he was well for the follow-up period of 3 months. To the best of our knowledge, this is the first such case that involved the skull.     

循环肿瘤细胞检测在预测非小细胞肺癌化疗疗效中的应用

目的 探讨循环肿瘤细胞检测在预测非小细胞肺癌化疗疗效中的应用.方法 选择非小细胞肺癌患者(肺Ca组)共25例,另选择慢性阻塞性疾病患者(COPD组)25例作为对比研究.入院后及化疗2个周期后分别采集所有参与研究的人员静脉血7.5 ml,利用密度梯度离心法富积循环肿瘤细胞,分析其与临床特征及化疗疗效的关系.结果 肺Ca组循环肿瘤细胞阳性率达72.00％,而COPD组阳性率为0,差异具有统计学意义(P<0.05).循环肿瘤细胞阳性表达与NSCLC病理类型、患者性别、年龄、吸烟情况等均无明显关系(P>0.05),仅与癌症分期相关(P<0.05).2个周期的化疗结束,发现对循环肿瘤细胞数目的评价与实体肿瘤疗效标准评价大致吻合,差异不具备统计学意义(P>0.05).相关分析发现这两种评价方法 呈负相关关系(γ=-0.465 P=0.021).结论 循环肿瘤细胞的存在与非小细胞肺癌的临床分期及化疗疗效有密切关系,可以用来预测非小细胞肺癌的转归.     

液体活检及其在非小细胞肺癌诊治中的研究进展

随着近几年科学技术的进步,液体活检技术也有了长足的发展,并在肿瘤的早期诊断及后期治疗中扮演着越来越重要的角色。相比于传统的组织活检,液体活检以其独有的无创性、便捷性、高重复性等特点在临床上得到更多的青睐,在未来有着巨大的发展潜力。本文重点探讨了循环肿瘤细胞（circulating tumor cells, CTCs）和循环肿瘤DNA（circulating tumor DNA, ctDNA）,作为液体活检最重要的两个检测对象,其历史、生物学特性,检测手段,局限性及其在非小细胞肺癌诊治中的应用。     

肺癌脑转移的治疗进展

肺癌脑转移的发生率高达25．4％～65％，占脑转移瘤的40％～60％，如果不治疗，平均生存期1～2个月。全脑放疗是传统有效的治疗手段，可提高中位生存时间4～5个月。立体定向放射治疗对〈4cm的转移灶疗效与手术相当。可使中位生存期达到9～15个月。而手术治疗在单发转移、肿瘤较大有明显占位效应致颅内压升高的患者可以获益。目前立体定向放射治疗和／或手术治疗＋／-全脑放疗＋／-化疗是肺癌脑转移的治疗模式，而分子靶向药物的治疗尚在探索之中。