The Clinical Usefulness of ^(99m)Tc-Tetrofosmin Scintigraphy in the Diagnosis of Lung Neoplasmas and Mediastinal Lymphoid Node Involvement

In order to investigate the clinical significance of 99mTc-Tetrofosmin （TF） scintigraphy in the evaluation of lung cancer and mediastinal lymphoid node involvement, 33 patients with pulmo- nary neoplasmas were subjected to both 99mTc-TF scintigraphies and CT scans in one week before their operations or puncturations. All the images were judged visually and the emission images were analyzed with semi-quantitative methods in addition. The results of each group were compared. There was marked difference in target/non-target （T/N） ratio between the lung cancer group and the benign lesion group （P〈0.001）. Moreover, in the lung cancer group, T/N ratio in tomographies was signifi- cantly higher than that in planar images （P〈0.01）. The sensitivity and accuracy of semi-quantitative analysis in 99mTc-TF SPECT were significantly higher than those of CT in the diagnosis of pulmonary neoplasmas （P〈0.05 and P〈0.01 respectively）, so was the sensitivity of 99mTc-TF SPECT vs CT in the diagnosis of mediastinal lymphoid node metastasis （P〈0.05）. It was also found that epidermoid squamous cell carcinomas and adenocarcinomas had a higher T/N ratio than in small cell carcinomas （P〈0.05）, and 2 h washout rate （WR） of adenocarcinomas was higher than that of epidermoid squamous cell carcinomas （P〈0.05）. In conclusion, 99mTc-TF scintigraphy showed a favorable diag- nostic accuracy in appraising lung cancers and mediastinal lymph node metastases. Furthermore semi-quantitative technology can improve the accuracy, and is potential to offer some information about histological type of the cancer tissue. Therefore, 99mTc-TF scintigraphy will be a useful tool in the diagnosis and staging of lung cancer.

Serum Vascular Endothelial Growth Factor Levels in Patients with Non-small Cell Lung Cancer and Its Relations to the Micrometastasis in Peripheral Blood

To examine the relationship between the levels of the serum vascular endothelial growth factor （VEGF） and the micrometastasis of peripheral blood in patients with non-small cell lung cancer （NSCLC）, 108 NSCLC patients, including 40 patients with benign lung diseases and 30 healthy controls, were investigated. The serum VEGF levels were detected by ELISA and CK19 mRNA in peripheral blood by reverse transcriptase-polymerase chain reaction （RT-PCR）. In NSCLC group, the serum VEGF levels and the positive rate of CK19 mRNA in peripheral blood were 479.8±268.5 pg/mL and 66.7%, which were significantly higher than those of the other two groups respectively （P〈0.01）, and both of them were increased significantly with the progression of clinical stage of the tumors （P〈0.01）. Serum VEGF levels as well as the positive rate of CK19 mRNA in different pathological types of lung cancer had no significant differences （P〉0.05）. Serum VEGF levels in the patients positive for CK19 mRNA was 561.7±325.6 pg/mL. It is significantly higher than that in the negative patients （P〈0.01）. There existed a significant correlation between serum VEGF levels and expression of CK19 mRNA in peripheral blood in NSCLC patients （P〈0.001）. The detection of serum VEGF levels and CK19 mRNA in peripheral blood is helpful in judging the condition and the prognosis of NSCLC patients, and serum VEGF levels and CK19 mRNA are independent of the pathological types of lung cancer. The micrometastasis in peripheral blood of NSCLC patients is significantly associated with serum VEGF levels.

Establishment and application of a multiplex genetic mutation-detection method of lung cancer based on MassARRAY platform

Objective: This study aims to establish a method for highly parallel multiplexed detection of genetic mutations in Chinese lung cancer samples through Agena i PLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on Mass ARRAY mass spectrometry platform.Methods: We reviewed the related literature and data on lung cancer treatments. We also identified 99 mutation hot spots in 13 target genes closely related to the pathogenesis, drug resistance, and metastasis of lung cancer. A total of 297 primers, composed of99 paired forward and reverse amplification primers and 99 matched extension primers, were designed using Assay Design software. The detection method was established by analyzing eight cell lines and six lung cancer specimens. The proposed method was then validated through comparisons by using a Lung Carta^(TM) kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases.Results: The proposed method was able to detect multiplex genetic mutations in lung cancer cell lines. This finding was consistent with the observations on previously reported mutations. The proposed method can also detect such mutations in clinical lung cancer specimens. This result was consistent with the observations with Lung Carta^(TM) kit. However, an FGFR2 mutation was detected only through the proposed method. The measured sensitivity and specificity were 100% and 96.3%, respectively.Conclusions: The proposed Mass ARRAY technology-based multiplex method can detect genetic mutations in Chinese lung cancer patients. Therefore, the proposed method can be applied to detect mutations in other cancer tissues.

NORTHERN BLOT ANALYSIS OF nm23 GENE EXPRESSION IN HUMAN LUNG CANCER

Objective: To investigate the role of nm23 gene expression in human lung cancer. Methods: Forty human lung cancer tissues and 19 non-cancer pulmonary tissues were studied for their nm23-H1 and nm23-H2 mRNA expression with non-radioactive Northern blot hybridization. The correlation of nm23 mRNA expression with clinical features of lung cancer was analyzed. Results: The mRNA expression of nm23-H2 gene in poorly differentiated squamous cell carcinoma was significantly decreased compared to that in moderate-high differentiated squamousd cell carcinoma. The mRNA expression of nm23-H1 and nm23-H2 gene in small cell lung cancer was significantly decreased compared to that in squamous cell carcinoma. No significant difference in nm23 mRNA expression was observed between lung cancer with and without lymph node metastasis, nor was there significant difference between tumor stage. Conclusion: The mRNA expression of nm23 gene is correlated with the degree of differentiation of lung cancer, but there is no evidence of metastasis suppression effect by nm23 gene.

SIGNIFICANCE OF ELECTRON MICROSCOPIC EXAMINATION IN THE DIAGNOSIS OF PULMONARY NEOPLASMS

The significance of electronic microscopc examination(EM) in the diagnosis of pulmonary neoplasms was evaIuated in 40 cases of Patients with different kinds of Pulmonary neoplasms.In 27 of the 40 cases,final diagnoses were made by light microscope(LM) examination,while in the remaining 13 cases,LM faded to reach definite diagnoses which were established with the help of EM.By analyzing our data,we conclude that in the following situations,EM helps meet in the diagnosis of pulmonary neoplasm:1.diagnosis of neuroendocrinal carcinomas of the lung;2.diagnosis of some rare pulmonary neoplasm;3.documentation of the histologic origins of the matastatic pulmonary neoplasms and 4.differentiation of malignant mesothelioma with pleural metastasis of Pulmonary adenocarcinoma.

Therapeutic effects of radio frequency ablation in lung tumor treatment

Objective:To assessthetherapeuticeffectsof radiofrequencyablation(RFA)inthetreatmentof patientswith unresectablemalignantlung tumors.Methods:Twentypatientswithprimaryor metastaticmalignantlungtumorsreceived RFAtreatment,andimaginganalysiswithCT,X-rayandpositionemissiontomograghy(PET)was performed1weekbe-foreand1to2weeksaftertreatment.Results and Conclusion:Postoperativefeveroccurredin6patientsandpneuma-tothoraxduringtheRFAprocedureswasfoundin5patients.PETdemonstratedthattumorssmallerthan3.5cm indiame-ter,whichis thegeneralcoverageof theRFAsystemwe adopted,dissipatedafterRFA,andtheproportionof the largertu-morswithinRFAcoveragewasdestroyed,whiletherestoutsideremainedintact.PETis currentlythemostreliabletech-niqueto observetheshort-termtherapeuticeffectsof RFAon tumorsincomparisonwithotherimagingapproaches.

Gastric metastasis of small cell lung carcinoma:Three case reports and review of literature

BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.

Combined Double Sleeve Lobectomy and Superior Vena Cava Resection for Non-small Cell Lung Cancer with Persistent Left Superior Vena Cava

A 65-year-old man with right central type of lung squamous carcinoma was admitted to our department.Bronchoscopy displayed complete obstruction of right upper lobe bronchus and infiltration of the bronchus intermedius with tumor.Chest contrast computed tomography revealed the tumor invaded right pulmonary artery,superior vena cava,and the persistant left superior vena cava flowed into the coronary sinus.The tumor was successfully removed by means of bronchial and pulmonary artery sleeve resection of the right upper and middle lobes combined with resection and reconstruction of superior vena cava(SVC)utilizing ringed polytetrafluoroethylene graft.To the best of our knowledge,this was the first report of complete resection of locally advanced lung cancer involving superior vena cava,right pulmonary artery trunk and main bronchus with persistant left superior vena cava.

Renal cell carcionoma with synchronous metastases to the bladder and lung

Renal cell carcinoma can metastasize to virtually any organ, yet synchronous metastasis to the bladder is extremely rare. A 77-year-old woman presented with gross hematuria. Abdominal and chest computed tomography showed a bilateral renal masses, bladder dome mass, and multiple lung metastasis. Transurethral resection of the bladder tumor and sonography guided renal biopsy were performed. Both pathology diagnoses were clear cell renal cell carcinoma. Targeted therapy using pazopanib was administered to the patient without surgical resection of primary tumors and metastatic lung lesions. Herein, we report the synchronous metastasis of renal cell carcinoma to the bladder and lung.

Skipping Metastasis to Mediastinal Lymph Nodes in Non-small Cell Lung Cancer: A Clinical Study on the Reasonable Extent of Dissection

Objective To elucidate the characteristics and metastastic pattern of skipping mediastinal lymph node metastasis (skipping N2) in non-small cell lung cancer (NSCLC), and investigate reasonable extent of lymph node dissection. Methods From 1990 to 1998, lobectomy combined with systematic mediastinal lymph node dissection was performed in 109 patients with NSCLC. A retrospective study was carried out to elucidate the characteristics of skipping N2 disease and to compare the difference between skipping N2 and non-skipping N2 diseases. Results Twenty-one patients (19%) had skipping N2 diseases. Of the skipping N2 group, 18 cases (86%) were adenocarcinoma. Skipping N2 disease was more common in T1 and T2 group than that in T3 and T4 group (P<0.01). All skipping N2 diseases only involved one nodal station, and most of them were regional mediastinal nodal metastasis. Skipping N2 from upper lobe tumors mainly involved superior tracheobronchial or subaortic lymph nodes, and skipping N2 from lower lobe tumors involved subcarinal lymph nodes. Conclusion Skipping N2 disease presents certain clinical characteristics and metastastic pattern, and mediastinal nodal dissection might be modified according to the pattern.

Deep learning model based on primary tumor to predict lymph node status in clinical stage IA lung adenocarcinoma:a multicenter study

Objective:To develop a deep learning model to predict lymph node(LN)status in clinical stage IA lung adeno-carcinoma patients.Methods:This diagnostic study included 1,009 patients with pathologically confirmed clinical stage T1N0M0 lung adenocarcinoma from two independent datasets(699 from Cancer Hospital of Chinese Academy of Medical Sciences and 310 from PLA General Hospital)between January 2005 and December 2019.The Cancer Hospital dataset was randomly split into a training cohort(559 patients)and a validation cohort(140 patients)to train and tune a deep learning model based on a deep residual network(ResNet).The PLA Hospital dataset was used as a testing cohort to evaluate the generalization ability of the model.Thoracic radiologists manually segmented tumors and interpreted high-resolution computed tomography(HRCT)features for the model.The predictive performance was assessed by area under the curves(AUCs),accuracy,precision,recall,and F1 score.Subgroup analysis was performed to evaluate the potential bias of the study population.Results:A total of 1,009 patients were included in this study;409(40.5%)were male and 600(59.5%)were female.The median age was 57.0 years(inter-quartile range,IQR:50.0-64.0).The deep learning model achieved AUCs of 0.906(95%CI:0.873-0.938)and 0.893(95%CI:0.857-0.930)for predicting pN0 disease in the testing cohort and a non-pure ground glass nodule(non-pGGN)testing cohort,respectively.No significant difference was detected between the testing cohort and the non-pGGN testing cohort(P=0.622).The precisions of this model for predicting pN0 disease were 0.979(95%CI:0.963-0.995)and 0.983(95%CI:0.967-0.998)in the testing cohort and the non-pGGN testing cohort,respectively.The deep learning model achieved AUCs of 0.848(95%CI:0.798-0.898)and 0.831(95%CI:0.776-0.887)for predicting pN2 disease in the testing cohort and the non-pGGN testing cohort,respectively.No significant difference was detected between the testing cohort and the non-pGGN testing cohort(P=0.657).The recalls of this model for predicting pN2 disease were 0.903(95%CI:0.870-0.936)and 0.931(95%CI:0.901-0.961)in the testing cohort and the non-pGGN testing cohort,respectively.Conclusions:The superior performance of the deep learning model will help to target the extension of lymph node dissection and reduce the ineffective lymph node dissection in early-stage lung adenocarcinoma patients.

肺癌患者血浆RASSF1A和BLU基因甲基化检测及临床意义

【目的】探讨肺癌患者外周血血浆中抑癌基因Ras相关结构域家族1A（RASSF1A）和BLU基因启动子的甲基化状态及其临床意义。【方法】利用巢式甲基化特畀性PCR（nMSP）法检测肺癌患者外周血血浆与正常人血浆中抑癌基因RASSF1A和BLU基因启动子的甲基化状态。【结果】58例肺癌患者血浆样品中分别发现22例（37．93％）RASSF1A基因启动子的异常甲基化和17例（29．31％）BLU基因启动予的异常甲基化，20例正常对照血浆中都未检测到RASSF1A和BLU基因启动子的异常甲基化，差异有显著性（P〈0．01）；但血浆中两基因甲基化检出率与患者性别、肺癌组织学分型及临床分期无明显相关性（P〉0．05）。【结论】利用nMSP法检测外周血血浆中RASSF1A和BLU基因启动子的甲基化，可为肺癌的筛查、早期诊断提供有用的信息。

20(R)-人参皂苷Rh_2抗B_(16)-BL6黑色素瘤转移的作用

目的:探讨20(R)人参皂苷Rh2抗B16-BL6黑色素瘤转移的作用及其机制。方法:采用B16黑色素自发转移模型观察Rh2对B16黑色素瘤转移的作用,观察Rh2对B16黑色素瘤细胞自身侵袭能力的影响。结果:在B16黑色素瘤自发肺转移的实验中,Rh2组C57BL/6N小鼠肺部转移结节数明显减少,Rh2作用后的B16黑色素瘤细胞侵袭人工基底膜能力明显下降。结论:Rh2可明显抑制B16黑色素瘤的肺转移,该作用可能与降低B16黑色素瘤细胞的侵袭能力有关。

c-Cbl、Cbl-b和EGFR在非小细胞肺癌中的表达及其预后价值

背景与目的表皮生长因子受体(epidermal growth factor receptor,EGFR)与肺癌的发展密切相关,其功能受泛素连接酶(Casitas B-lineage lymphoma,Cbl)家族调节,本研究旨在探讨c-Cbl、Cbl-b和EGFR在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其在预后判断方面的应用价值。方法采用组织微阵列联合免疫组织化学染色技术检测94例NSCLC组织中c-Cbl、Cbl-b、EGFR的表达,分析其与临床病理因素及预后之间的关系。结果 c-Cbl、Cbl-b和EGFR的阳性表达率分别为30.9%(29/94)、84.0%(79/94)和60.6%(57/94)。c-Cbl、Cbl-b蛋白表达与年龄、病理类型、TNM分期、淋巴结有无转移及吸烟史无关。EGFR、c-Cbl、Cbl-b的表达与患者的总生存无明显相关。亚组分析显示,在EGFR阳性组患者中,c-Cbl阳性组患者的总生存期(overall survival,OS)明显优于c-Cbl阴性组的患者(P=0.014)。结论检测c-Cbl蛋白的表达水平可能有助于预测EGFR阳性NSCLC患者的预后。

C57/BL小鼠TGF-β_1、TNFα在不同照射剂量下的表达及与放射性肺损伤的关系

目的 探讨转化生长因子 β1(TGF β1)及肿瘤坏死因子 α(TNF α)在不同照射剂量下的变动情况及与放射性肺损伤的关系。方法 雄性C5 7/BL小鼠 ,右肺单次照射 15MeV电子线 6Gy或 10Gy ,不同时间处死后取肺组织HE染色 ,同时ELISA法测定血清中TGF β1及TNF α。结果 不同剂量照射后 ,血清TGF β1平均水平 10Gy组较 6Gy组、正常对照组高 ,有显著性差异 (P <0 .0 5 ) ;6Gy组与正常对照组比较无显著性差异 (P >0 .0 5 )。各组间血清TNF α平均水平比较情况同TGF β1。HE染色病理切片不同时段 (照射后 36h～ 4 0d)显示 ,10Gy照射组肺照射区域内出现进行性加重的炎症改变 ,但并不严重 ;6Gy组受照肺组织与正常肺组织基本无差别。结论 放射性肺损伤的原因是多因素的。血清中TGF β1、TNF α的变化情况与照射剂量关系密切。

脐带间充质干细胞对C57BL/6小鼠Lewis肺癌生长及转移的影响

目的利用Lewis肺癌动物模型探讨脐带来源的间充质干细胞(MSC)对肺癌生长及转移的影响。方法用16只C57BL/6小鼠分别建立Lewis肺癌模型,并随机分为对照组(NS组)和MSC组,每组8只。MSC组分别于接瘤后第7、12、17天时,尾静脉注射脐带MSC(1×106/只),在第21天时处死全部荷瘤小鼠,观察瘤体生长情况及肺转移情况。结果 NS组和MSC组的平均瘤体质量分别为(4.587 5±1.04)g、(4.155±1.13)g,两组相比差异无统计学意义(P=0.59)。NS组和MSC组的平均肺转移数分别为(3.75±1.39)个、(1.13±1.13)个,两组相比差异有统计学意义(P<0.01);抑制转移率为70.0%。结论脐带来源的MSC对C57BL/6小鼠Lewis肺癌本身的生长无影响,但能够抑制肿瘤的转移。

Relationship between the Expression of E-cadherin and Microvessel Density in Lung Cancer and Its Significance

To study the relationship between the expression of E-cadherin andmicrovessel density (MVD) in lung cancer. Methods: The expression of E-cadherin and factor VIII wasdetected in 104 lung cancer tissues by an immunohistochemical method, and MVD was calculated by animage-analysis system. Results: The expression of E-cadherin was significantly related to thedifferentiation of lung cancers (P 【 0.05). A negative correlation was found between E-cadherinexpression and MVD in lung cancer tissues (P=0.047). Conclusion: Down-expression of E-cadherin andan increase of MVD may play an important role in the invasion and metastasis of lung cancer, and mayalso be used as a useful marker for tumor prognosis.

Cbl-b基因介导T细胞免疫杀伤小鼠LA795肺腺癌细胞的实验研究

目的利用特异性小干扰RNA(small interfering RNA,siRNA)沉默T细胞Cbl-b基因表达,观察转染T细胞对小鼠肺腺癌细胞LA795的体外免疫杀伤作用。方法筛选高效特异性沉默Cbl-b基因的siRNA序列转染T739小鼠脾脏T细胞,转染72h后,利用酶联免疫吸附法(ELISA)检测IL-2、INF-γ等T细胞免疫因子分泌情况,比较单纯T细胞、阴性对照T细胞及转染T细胞与小鼠肺腺癌细胞LA795混合培养肿瘤杀伤率。结果转染72h后,转染组细胞因子IL-2、INF-γ分泌水平较空转组和空白组显著增加。在体外实验中,与单纯T细胞及阴性对照T细胞相比,转染T细胞能更高效杀伤小鼠肺腺癌细胞LA795,最高杀瘤率达到58.38±3.82%。结论利用特异性siRNA技术沉默Cbl-b基因能够促进小鼠T细胞因子IL-2和INF-γ分泌,增强T细胞对肺腺癌细胞LA795的体外免疫杀伤作用。

Clinical Course Of Patients with Small Cell Lung Cancer As Second Primary Malignancy

Objective： To evaluate the clinical course of patients with small cell lung cancer （SCLC） as second primary malignancy. Methods： Among the 355 patients diagnosed with SCLC at Helen and Harry Gray Cancer Center of Hartford Hospital Connecticut USA between 1988 and 1998, the records of 48 patients, which had been diagnosed with other malignancies before their diagnosis of SCLC, were retro- spectively reviewed. Results： Forty-eight patients （13.5%） were diagnosed with other malignancies prior to their SCLC among which 43 had documented smoking history and 93% of them （40/43） were current/former smokers. Of the 28-second primary SCLC patients who were treated with standard method, 11 （39.3%） achieved CR. 12 （42.8%） achieved PR, and the RR was 82.1%. The median survival of the 28 treated with standard method was 11.3 months （5.1-77.7 months）, while that of the rest 19 untreated patients （1 of 20 was lost to follow-up） was only 2.0 months （0.5 34.0 months）. There was no significant difference in the median survival and RR between 165 treated first primary SCLC （13.5 months and 77.6% respectively） and 28 treated secondary primary SCLC （11.3 months and 82.1% respectively） （P〉0.05）. The patients who had prostate cancer were older and subjected to less treatments than those with skin cancer, so their survival was shorter than the latter （3.5 months vs. 15 months, P〈0.05）. Conclusion： The response and survival of the treated patients with SCLC as a second malignancy showed no difference as compared to the treated ones with SCLC only. Therefore, an active medical treatment is important to relieve symptom and prolong survival of the second primary SCLC patients.

非小细胞肺癌中MAGE-3蛋白的Western Blot分析

目的:观察黑素瘤抗原-3(MAGE-3)蛋白在非小细胞肺癌(NSCLC)中的表达。方法:用Western blot方法对3种人肺癌细胞系和56例NSCLC标本及相邻正常肺组织标本MAGE-3蛋白的表达情况进行研究。结果:3种人肺癌细胞系均表达MAGE-3蛋白;56例NSCLC标本中,28例表达MAGE-3蛋白,而相邻正常肺组织均不表达MAGE-3蛋白。结论:MAGE-3蛋白在NSCLC中有较高比率的表达,有望以该抗原作为适宜靶点对NSCLC患者进行免疫治疗。