SHR-A1201 is an antibody–drug conjugate (ADC) that combines trastuzumab with DM1 (a chemotherapeutic agent) using a chemical connector. This phase I study investigated the safety, tolerability and pharmacokinetics of SHR-A1201 in patients with human epidermal growth factor receptor 2-positive advanced breast cancer. This phase I study enrolled patients in a traditional 3 + 3 dose-escalation design to receive a single dose of SHR-A1201 (1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg or 4.8 mg/kg). The observation period of dose-limiting toxicity (DLT) was 21 days. A total of 12 patients were enrolled and received SHR-A1201. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity, with elevated aspartate aminotransferase (75%), thrombocytopenia (75%), and nausea (66.7%) being reported most frequently. The common grade 3 TEAEs were thrombocytopenia and decreased lymphocyte count, and there were no grade 4 or above TEAEs. There were no serious adverse events or drug-related deaths. One DLT occurred in one patient treated with SHR-A1201 4.8 mg/kg (asymptomatic grade 3 increased γ-glutamyltransferase). The maximum tolerated dose of SHR-A1201 was not lower than that of T-DM1 (3.6 mg/kg). A total of 8.3% (1/12) of patients had ADA-positive reactions 504 h after administration, but no differences were observed in the type, incidence, or severity of TEAEs between patients with and without ADA. SHR-A1201 exhibited the pharmacokinetics characteristics of typical ADCs. An encouraging antitumor effect was observed in the 4.8 mg/kg dose group. SHR-A1201 was well tolerated and safe in patients with advanced HER2-positive breast cancer. The pharmacokinetics parameters showed a linear trend, and the immunogenicity results met the clinical expectations.

目的 探讨曲妥珠单抗对人表皮生长因子受体2(HER2)阳性Ⅳ期乳腺癌的治疗效果及患者预后的影响因素.方法 收集229例应用曲妥珠单抗治疗的HER2阳性Ⅳ期乳腺癌患者的临床资料,采用Cox比例风险回归模型分析HER2阳性Ⅳ期乳腺癌患者无进展生存时间(PFS)和总生存时间(OS)的影响因素.结果 229例HER2阳性Ⅳ期乳腺癌患者行曲妥珠单抗总体治疗的客观有效率为44.5％,疾病控制率为90.8％,中位PFS为10个月(95％CI:8.748～11.252),中位OS为29个月(95％CI:27.551～30.449).单因素分析结果显示,激素受体状态和曲妥珠单抗不同线治疗均可能与HER2阳性Ⅳ期乳腺癌的PFS有关,激素受体状态、曲妥珠单抗不同线治疗和进展后是否继续行曲妥珠单抗治疗均可能与HER2阳性Ⅳ期乳腺癌的OS有关(P﹤0.05).多因素分析结果显示,激素受体状态和曲妥珠单抗不同线治疗是HER2阳性Ⅳ期乳腺癌PFS和OS的独立影响因素(P﹤0.05).结论 一线应用曲妥珠单抗是治疗HER2阳性Ⅳ期乳腺癌的有效手段,在治疗进展后继续应用曲妥珠单抗治疗仍有生存获益.

目的 研究原发性双侧乳腺癌患者的临床特征,为临床诊疗提供更多有价值的依据.方法 收集原发性双侧乳腺癌患者共31例,采集患者的临床资料,如年龄、肿瘤大小、淋巴结转移数目、激素受体状态、肿瘤初诊方式等.结果 原发性双侧乳腺癌第二原发癌的初诊肿瘤大小(T)较第一原发癌偏小(P＜ 0.05),TNM分期较第一原发癌更早(P＜0.05);第二原发癌的TNM分期以0期或Ⅰ期较为多见.原发性双侧乳腺癌第一原发癌与第二原发癌的激素受体状态比较,差异无统计学意义(P＞0.05).原发性双侧乳腺癌第一原发癌与第二原发癌通过自检发现的比例分别为64.5％、41.9％,由临床医师手诊、超声及钼靶X线检查发现的比例分别为35.5％、58.1％,其中有2例(6.5％)对侧乳腺癌漏诊,通过MRI检查发现.结论 对于已罹患乳腺癌的患者,应定期进行对侧乳房检查并结合钼靶、超声或MRI等影像学检查,对可疑病灶予以积极处理,从而提高对侧乳腺癌的早期诊断率,进而提高双侧乳腺癌的诊疗效果.

Objective To study the clinical pathological features between the subtypes of the female mucinous breast cancer with its prognosis.Methods Eighteen cases confirmed as pure mucinous breast cancer (PMBC) with complete case report and follow-up information in Beijing Shijitan Hospital was collected and divided into type A PMBC and type B PMBC. A retrospective analysis was performed for both groups on clinical and pathological features and prognosis.Results The axillary metastasis rate for type A PMBC was 13.3%, and 0 for type B PMBC. The distant metastasis rate for type A was 6.7%, and 0 for type B. The percentage of ER and PR positive cases for type A was 93.3% and 86.7%, respectively, and was both 33.3% for type B. The HER-2 gene overexpression rate was both 0 for type A and B. And for Ki-67 expression, the low and high expression rate for type A was 80.0% and 20.0%, respectively, and was 100.0% and 0 for type B, respectively.Conclusions PMBC is a special subtype of the breast cancer with good prognosis. The pathological features and biological behavior between type A and type B is different. Further research and more data will be needed to access the prognosis with the classification.

Objective To investigate the value and feasibility of wire-location surgical biopsies by mammograpy three- dimensional positioning system for non- palpable breast lesions. Methods Between April 2013 and October 2015, sixty-seven women with non-palpable breast lesions underwent surgery at Beijing Shijitan Hospital. Wire localization guided by mammograpy three- dimensional positioning system was performed before operation. Results All lesions founded out by mammograpy were accurately localized and excised. Seventeen cases (25.4%) were malignant, 13 (19.4%) were precancerous lesions (including ductal atypical hyperplasia and intraductal papilloma), and cases 37 (55.2%) were benign lesions by pathologic diagnosis. 34.8% (16/46) cases with microcalcifications were malignant, 17.4% (8/46) were precancerous lesions, and 47.8% (22/46) were benign lesions. In non-calcification group, 95.2% (20/21) were benign lesions and 4.8% (1/21) were malignant. By statistical analysis, the detection rate of breast cancer was higher in the cases with microcalcifications (χ2=5.369, P=0.021). Conclusion Careful consideration should be taken for the cases of non-palpable breast lesions, and mammograpy three-dimensional positioning system-guided wire localization of breast lesions is useful in assisting surgical biopsy and worth extensive generalization.

目的:检测非恶性肿瘤患者胆汁中CA19-9含量并分析其临床意义.方法:选取2008-1 1-01-2011-10-31首都医科大学附属北京世纪坛医院肿瘤中心非恶性肿瘤患者61例,其中6例胃溃疡,22例结直肠腺瘤或息肉,17例胆囊结石,16例胆囊腺瘤或息肉.手术前采取外周静脉血液标本5 mL,手术中胆汁胆囊采集胆汁标本10 mL.采用微球酶联免疫分析法进行检测.所有病例随访1～4年.结果:61例患者外周血清中CA19-9含量为(5.93±4.06) U/mL,属于正常水平,其中胃溃疡组为(7.13±6.37) U/mL,结直肠腺瘤或息肉组为(5.56±3.52) U/mL,胆囊结石组为(5.46±4.27) U/mL,胆囊腺瘤或息肉组为(6.48±3.79) U/mL.各组间比较差异无统计学意义,P=0.2.胆囊胆汁中CA19-9含量为(290 174.96±389 985.78) U/mL,其中胃溃疡组为(219 334.77±213 246.13) U/mL,结直肠腺瘤或息肉组为(327 754.85±489 632.47) U/mL,胆囊结石组为(263 567.54±268 466.28) U/mL,胆囊腺瘤或息肉组为(293 338.07±419 274.36) U/mL.各组间差异无统计学意义,P=0.3.胆囊胆汁中CA19-9含量明显高于外周血清中CA19-9含量,P=0.005.有7例患者胆囊胆汁中CA19-9含量较低,为(4.21±2.34) U/mL;另外54例患者胆囊胆汁中CA19-9含量极高,为(327 789.69±399 517.12) U/mL.两组间差异有统计学意义,P=0.002.随访期间,没有肿瘤发生,目前生存59例,1例死于心肌梗死,1例死于脑卒中.结论:部分非恶性肿瘤患者胆汁中CA19-9含量极高,可能原因是患者胆管和胰管上皮细胞合成和分泌CA19-9.单独胆汁中CA19 9含量升高并不能作为恶性肿瘤的诊断依据.

目的:对比不同剂量顺铂循环热灌注治疗胃肠道肿瘤腹水的近期疗效及副反应,并对其安全性进行评估.方法:同期胃肠道肿瘤腹水患者102例,随机分为两组,通过腹腔内穿刺置双管建立循环双通路,先行单向灌洗放出腹腔积液,再行循环热灌注.观察组于灌注液中加入顺铂120mg,并静脉给予硫代硫酸钠解救,对照组于灌注液中加入顺铂40mg,两组同时常规水化、利尿、止吐,两周期后对其疗效及副反应进行比较.结果:两组102例患者两个疗程后全部可评价疗效,观察组有效率90.7％,明显高于对照组,两组间差异有统计学意义(P＜0.01),毒副反应均较轻微,经对症处理,很快恢复正常,差异无统计学意义(P＞0.05).结论:大剂量顺铂腹腔内循环热灌注加硫代硫酸钠治疗胃肠道肿瘤腹水近期疗效明显,创伤性小,不良反应少而轻

Objective To compare the efficacy and complications of high-dose cisplatin loop perfusion with simple infusion chemotherapy for the treatment of gastrointestinal tumor ascites.Methods 103 cases of gastrointestinal tumor patients with ascites were divided into two group.Observed group was given high-dose hot cisplatin and the temperature was 43℃.Control group was given high-dose cisplatin without hot temperature,after 24 hours to release liquid.Results Two groups of 103 patients after two courses of all efficacy evaluation,efficient of observation group was 90.7%,significantly higher than the control group(51.0%).There was a statistically significant difference between two groups(P 0.01).The side effects were minor and there was no statistically significant difference between two groups(P 0.05).Conclusion Circulating the hot irrigation with large dose along the platinum treatment gastro-intestinal tract tumor ascites is security.Side effects are few and light and the short-term effect is obvious.

Objective To explore the circulating hot infusion of high dose cisplatin in the treatment of gastrointestinal cancer ascites effect and analysis of its complications. Methods 29 cases of ascites in patients with gastrointestinal tumor through puncture with double tubes and established cycle double-pathway, one-way lavage released ascites. Further circulation perfusion, and joined the high-dose cisplatin in infusion liquid to observe its effects and complications. Results Of this group of 29 cases of patients being circulation perfusion after high-dose cisplatin the two course evaluation of efficacy, including complete remission 9, cases, part mitigation 16 cases, stability 3 cases, invalid 1 cases, has efficiency 86.2%, 16 cases (55.2%) patients appears gastrointestinal road reaction, 9 cases (31.0%) patients appears white cell fell, all patients in the is not appears kidney toxicity, and ear toxicity, and peritoneal inflammatory, and intestinal adhesion, and intestinal obstruction. Conclusion Loop infusion high dose cisplatin chemotherapy in the treatment of gastrointestinal tumor ascites safe, minimally invasive, less side effects and recent effect of light and obvious.

Objective To investigate the expression and significance of matrix metalloproteinase-7(MMP-7),matrix metalloproteinase-9(MMP-9),and tissue inhibitor of matrix metalloproteinase-3(TIMP-3)in osteoarthritis patients' synovium of knee joint.Methods The histological changes of synovium of knee joint was examined by hematoxyllin-eosin staining and immunohistochemical expression of MMP-7,MMP-9,TIMP-3 in osteoarthritis in 20 osteoarthritis cases and 20 normal controls.All data were statistically analyzed by χ2 test and correlation analysis.Results The Immunohistochemical expression of MMP-7,MMP-9,TIMP-3 in the osteoarthritis patients' synovium of knee joint was significantly more higher than that in the normal synovium(P 0.05).Conclusion The abnormal expression of MMP-7,MMP-9,TIMP-3 in osteoarthritis patients' synovium of knee joint is likely to be the more important index of diagnosis.

OBJECTIVETo explore the short-term clinical effects on application of absorbable RIGIDfix cross pins and Intrafix screw for posterior cruciate ligament (PCL) reconstruction with autogenetic or xenogenic semitendinosus-plus-semimembranosus tendons under arthroscope.METHODSFrom June 2005 to January 2007, 36 cases of PCL injuries (including 20 fresh injuries and 16 old ones) were treated. There were 21 males and 15 females, aged 15-51 years old, mean 30.4 years. There were 19 cases in the left side and 17 cases in the right side. Thirteen cases out of them complicated with medial collateral ligament injury; 9 cases complicated with lateral collateral ligament injury; 2 cases complicated with posterolateral structure injury; 11 cases complicated with medial meniscus injury; 10 cases complicated with lateral meniscus injury; 2 cases complicated with nerve and vascular injury. PCL reconstruction was accomplished by arthroscopy with autogenetic or xenogenic 4-strand semitendinosus-plus-semimembranosus tendons. RIGIDfix cross pins were used for tibial side fixation, and Intrafix was used for femoral side fixation. Lysholm scores, international knee documentation(IKDC) grading and Lachman experiment were used for evaluation before operation and in the follow up.RESULTSAll the cases had been followed up for 6 to 26 months (average 10.4 months). IKDC grading showed that 3 patients (8.4 %) were graded as B, 12 patients (33.3%) as C, 21 patients (58.3%) as D before operation, while 9 patients (25 %) were graded as A, 21 patients (58.3%) as B, 6 patients (16.7%) as C after operation. Lysholm scores raised from 42.52 +/- 5.24 before operation to 91.24 +/- 5.68 after operation. Lachman experiment results showed that there were 5 cases (+), 20 cases (++) and 11 cases (+++) before operation, while there were 2 cases (+) and 34 cases (-) after operation. Each index was significant between before and after surgery (P < 0.05). After surgery, all the cases got good pain relief. Joint was stable, and motion range recovered. No pin and screw loosening was found. Only 4 cases suffered from effusion and synovitis after surgery, and they were recovered after conservative treatment.CONCLUSIONThe method of using RIGIDfix-Intrafix complexes under arthroscopy for PCL reconstruction is simple and the fixation is rigid. Early functional exercise after operation is possible.

[Objective] To introduce surgical approach and evaluate therapeutic effect of anterior cruciate ligament(ACL) double-bundle reconstruction with allograft hamstring.[Methods] The experimental group includes 18 cases who accepted double bundle ACL reconstruction with allograft hamstring while the control group includes 28 cases who accepted single-bundle ACL reconstruction with allograft hamstring.The evaluation methods were clinical examination,Lachman test and pivot shift test,radiographic evaluation such as CT MRI,as well as International Knee Documentation Committee,Irgang and Lysholm knee scores.[Results] All of the 46 patients were followed up with an average of 9 months(range from 6~11 months).All patients were radiographically in good position and had comfortable joint function.Experimental group:Lysholm score(83.6±9.2),Irgang score(78.8±8.2),16 patients got normal IKDC Score(83.3%),15 patients got normal and 3 got nearly normal result in Lachman test while 16 patients got normal and 2 got nearly normal result in pivot shift test.Control group:Lysholm score(83.2±8.8),Irrgang score(77.9±8.3),23 patients got normal IKDC Score(82.14%),23 patients got normal,4 got nearly normal and 1 got abnormal result in Lachman test while 22 patients got normal,5 got nearly normal and 1 got abnormal result in pivot shift test.[Conclusion] Double-bundle ACL reconstruction with allograft hamstring can improve rotational stability.The clinical result of our test might indicate an optimistic application in the future.

乳腺癌是严重威胁广大妇女健康的疾病之一.近年来,由于普查技术的广泛开展,早期乳腺癌的病例数不断增加,保乳手术的开展也随之不断增多.保乳术后的乳房放疗已成为放疗的重要研究课题之一.特别是乳房部分放疗(APBI)是目前世界上研究的重点.MammoSite是目前乳房部分放疗的重要装置[1],国外已经开展3年,国内尚未开展,现将其有关应用的情况作一介绍.

乳腺癌是严重威胁女性健康的恶性肿瘤.在美国,约12%的女性会在有生之年患乳腺癌,即每8位女性中会有1人患乳腺癌[1].随着我国人民生活水平的不断提高,乳腺癌的发病率也呈逐年上升的趋势,年增长率达到2%,在城市,乳腺癌已成为女性最常见的恶性肿瘤.因此乳腺癌的预防极为重要.乳腺癌的预防分为3级,一级预防即病因预防相对较难做到;三级预防多数为进展期病例的治疗,治愈率相对较低;二级预防即筛查或普查是延长乳腺癌存活时间的有效方法.在世界范围内,乳腺癌的普查最早开展于20世纪60年代,我国部分地区也有开展.现将乳腺癌普查的国内外进展做一介绍.

ObjectiveTo investigate the feasibility, security, and short-term efficacy of combined treatment of interstitial implantation of ~ 125 I seeds and 5-FU slow-released seeds for recurrent colorectal adenocarcinoma. Methods From December 2001 to December 2005, 26 cases of recurrent colorectal adenocarcinoma underwent Mile's procedure were treated with the radiochemotherapy.We implanted alternately ~ 125 I seeds and 5-FU slow-released seeds following the treatment planning system.The matched peripheral dose (MPD) of ~ 125 I seed implantation was 90-130 Gy. Twelve granules of ~ 125 I seeds and 600 mg of 5-FU were administered in every patient on average. Results No operation-related complication was occurred during the implantations for all the cases. No displacement of ~ 125 I seed was found by pelvic X-ray examination.Lenitive rate of the pain was 88.9% (16/18).The relief has lasted for 5-10 days on average. CT scanning showed that the size of tumor reduced in various degree at 3-6 months after the implantation.The complete recovery rate was 7.7% (2/26), the partial recovery rate was 73.1% (19/26).The PD was 15.4% (4/26).The median survival time was 29 months estimated by following these cases for 6-42 months. One case died of bone and lung metastases at 6 months after the implantation. ConclusionCombined radiochemotherapy with interstitial implantation of ~ 125 I seeds and 5-FU slow-released seeds was a safe and effective microinvasive treatment for recurrent colorectal carcinoma.

目前在进展期胰腺癌的综合治疗体系中,以手术切除为主的综合治疗仍占据着主导地位.但有时由于病变的特殊性使病人失去了根治切除的机会,此时应用术中放射性粒子植入的方法治疗进展期胰腺癌具有一定意义.本文从以下几个方面进行探讨.

2001年9月～2002年6月,我们应用放射性粒子碘125治疗晚期胰腺癌9例,现报告如下.

目的以Wistar大鼠作为实验模型,观察胃肠道术后早期腹腔大剂量大体积灌注放射性导向药物对吻合口愈合可能产生的影响.方法 Wistar大鼠32只,在距离盲肠3 cm处切断升结肠,然后作端端吻合.术后将大鼠分为四组,24小时腹腔分别注射如下:A组:131I-3H11 10 mCi/NS 40 ml/kg;B组:131I-3H11 5 mCi/NS 40 ml/kg;C组:131I-3H11 1 mCi/NS 40 ml/kg;D组:NS 40 ml/kg.结果 (1)各组动物食欲佳,生活状态良好,体重有所增加,各组间差异无显著性,各组大鼠外周血白细胞数目变化不明显;(2)术后第14天处死大鼠剖腹观察,各组大鼠腹壁切口均一期愈合,未发生感染,未见腹水;(3)各组大鼠结肠吻合口愈合佳,无狭窄及渗漏,张力强度分别为(296.25±19.82)g、(293.38±13.28)g、(293.25±24.37)g和(287.88±13.61)g,各组间比较差异无显著性.结论术后早期大剂量大体积腹腔灌注131I-3H11对大鼠无明显毒性作用,不影响腹壁切口和结肠吻合口愈合.

近年来,世界各国逐渐规范白蛋白的使用指征.本文综述介绍白蛋白在外科营养中的作用,为合理的营养提供和正确使用白蛋白制剂提供理论参考.

诺贝尔奖获得者Feynmen早在1959年就指出,在设定的空间内人们可以利用特定的技术逐个原子地制造物质.1984年Gleiter等[1]首次用惰性气体蒸发原位加热成功制备具有清洁表面的纳米材料.目前,人们正广泛地探索新型纳米材料,系统研究纳米材料的性能、微观结构、谱学特征及应用前景,取得了大量具有理论意义和重要应用价值的结果.纳米材料已成为材料科学和凝聚态物理领域中的热点,是当前国际上的前沿研究课题之一.现将纳米技术在肿瘤防治方面的研究进展作一介绍.