直肠癌同时性肝转移的外科治疗

目的探讨直肠癌同时性肝转移外科治疗手术时机及方法。方法对2006年8月至2008年8月在我中心32例直肠癌同时性肝转移患者的诊断和治疗的临床资料进行回顾性分析。结果术前B超、CT、MRI能够明确诊断直肠癌肝转移灶能否手术切除;术前新辅助化疗及靶向治疗可以进一步筛选直肠癌肝转移;治疗模式是以手术为主的综合性治疗。结论可切除的直肠癌肝转移首选手术治疗;采取合适的、个体化综合治疗手段能够提高无瘤生存率和累计生存率。     

Recent advances in the treatment of hormone receptor positive HER2 negative metastatic breast cancer

Endocrine therapy is the recommended systemic therapy for hormone receptor (HR) positive metastatic breast cancer (MBC).However so far the limited number of endocrine agents and the onset of endocrine resistance have severely limited the therapeutic options for this patients.In the last years many targeted agents have been investigated to prevent or overcome endocrine resistance; only a few of them have been found effective in HR positive MBC, such as everolimus, CK4/6 inhibitors and HDAC inhibitors.Furthermore, translational medicine studies using next generation sequencing technologies have evaluated genetic variations of a broad panel of cancer-related genes and explored their correlations with targeted agents benefit. In some studies predictive biomarkers have been identified and many ongoing studies are evaluating the efficacy of targeted drugs in HR positive MBC patients selected for biomarkers or stratified by pathways amplification.     

Adjuvant therapy for HER2 positive pT1a-b pN0 breast cancer: A single center cohort study

Deciding if patients with small (≤1 cm), node-negative, human epidermal growth factor receptor 2 (HER2) positive breast cancer should receive adjuvant systemic therapy remains a challenge. No randomized clinical trials have examined the efficacy of trastuzumab in this setting. This prospective observational study aimed to investigate the choice of adjuvant systemic therapy in clinical practice in China.We prospectively collected data from patients with HER-2 positive breast cancer (less than 1 cm and node negative) patients who underwent breast cancer surgery at Shanxi Provincial People''s Hospital Breast Center from January 1, 2017 to December 31, 2019, and retrospectively investigated the association between baseline clinicopathological features and treatment strategy, cardiotoxicity, and disease outcome.Of 168 eligible patients, 102 (60.7%) received adjuvant systemic therapy with trastuzumab (AST+T), 47 (28%) received adjuvant systemic therapy without trastuzumab (AST) and 19 (11.3%) did not receive adjuvant systemic therapy. Multivariate logistic regression analysis demonstrated that age, tumor size and hormone receptor status were significantly associated with treatment choice. Three-year invasive disease-free survival probability was 100%, 97.9% and 89.5% with AST+T, AST, and no therapy, respectively (P < .001).The majority of patients (60.7%) with pT1a-b pN0 HER2 positive breast cancer received adjuvant systemic therapy with trastuzumab, whereas only 11.3% did not receive any adjuvant systemic therapy. Tumor size, age and hormone receptor status influenced treatment choice. The 3-year invasive disease-free survival probability was significantly higher for patients who received adjuvant systemic therapy with trastuzumab compared with those who did not receive adjuvant systemic therapy. Cardiac adverse events were rare.     

Recent applications of chemosensitivity tests for colorectal cancer treatment

The evaluation of therapeutic efficacy is necessary to predict the outcome of patients with metastatic colorectal cancer(CRC). In these patients, there is a critical need for predictive chemosensitivity assays and biomarkers to optimize efficacy and minimize toxicity. The introduction of targeted agents has improved the progression-free survival and overall survival of patients with metastatic disease. However, approximately 50% of patients do not show a positive response to chemotherapy and the selection of patients likely to respond to a specific regimen remains challenging. Cell culturebased chemosensitivity tests use autologous viable tumor cells to evaluate susceptibility to specific agents in vitro and predict their direct effects. Adenosine triphosphate-based assays and methyl thiazolyl-diphenyltetrazolium bromide-based assays are used widely as sensitivity tests because of their short assay period, technical simplicity, and the requirement of small amount of specimen. Among protein- and gene-based chemosensitivity assays, assessment of KRAS mutation status predicts the response to epidermal growth factor receptor-targeted therapy in CRC patients. The validation of predictive and prognostic markers enables the selection of therapeutic regimens with optimal efficacy and minimal toxicity for each patient, which has been termed personalized treatment. This review summarizes currently available predictive and prognostic chemosensitivity tests for metastatic CRC.     

Combined therapies for cancer: a review of EGFR-targeted monotherapy and combination treatment with other drugs

Targeted therapy refers to anticancer treatment which specifically targets key molecules of cancer cells and/or neovascular cells, aiming to thus interfere with processes of tumorigenesis, cancer progression and metastasis. The epidermal growth factor receptor (EGFR) was the first receptor to be proposed for targeted cancer therapy, having been found to be commonly overexpressed in a range of solid tumors and play a role in cancer cell proliferation, apoptosis, angiogenesis, invasion and metastasis. Despite successful development of EGFR-targeted pharmacological agents, clinical and molecular studies have indicated several limitations to the broad application of this treatment as a monotherapy. Novel combination treatments which might optimize the effect of EGFR inhibition have, therefore, been investigated. Research conducted into the mechanisms of action and synergy of these combination treatments is likely to enhance the role of the EGFR target in future cancer treatment.     

全身化疗联合经肝动脉化疗栓塞术治疗乳腺癌肝转移的疗效观察

目的探讨发生肝转移的乳腺癌患者采用全身化疗联合经肝动脉化疗栓塞术(TACE)治疗的效果。方法选取2012年12月-2014年12月于山东省医学科学院附属医院接受治疗的乳腺癌并发肝转移女性患者86例,将其平均分为试验组和对照组。对照组采用全身化疗,试验组给予全身化疗基础上联合TACE治疗,比较2组临床疗效、病灶变化情况以及治疗后患者生活质量评分情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果试验组患者治疗的总有效率高于对照组,差异有统计学意义(90.70%vs 58.14%,χ2=13.07,P=0.001);与对照组相比,试验组患者治疗后肿瘤直径、淋巴结直径较小,差异均有统计学意义(t值分别为4.26、4.63,P值均0.001);试验组患者治疗后3、6个月生活质量评分均高于对照组,差异均有统计学意义(t值分别为6.30、3.89,P值均0.001)。结论对乳腺癌肝转移患者采用全身化疗联合TACE治疗的效果显著,能够改善患者症状,减少药物不良反应,提高生活质量,且安全可靠,值得推广应用。     

重视中晚期肝癌的降期转化治疗

外科手术治疗是肝癌获得根治和长期生存的最有效途径。目前,大部分中晚期肝癌患者不能获得根治性手术治疗。临床实践中需高度关注并深入探讨中晚期肝癌的降期转化治疗策略,进一步提高疗效。根据中晚期肝癌患者的不同分期和具体病情,多学科团队协作,优化降期转化治疗方案,有望使不能手术切除的患者获得手术治疗,姑息性治疗转化为根治性手术切除,不能抗肿瘤治疗的患者可接受姑息性治疗,更多的中晚期肝癌患者疗效提高,预后改善,长期生存。     

后程三维适形放疗联合紫杉醇化疗治疗老年人乳腺癌伴脑转移癌的临床观察

目的 观察后程三维适形放疗(3D-CRT)联合紫杉醇同步化疗治疗老年乳腺癌伴脑转移癌患者的疗效及不良反应.方法 50例患者随机分为观察组(放疗加化疗组,26例)和对照组(单纯放疗组,24例).两组前程全脑均行普通二维放疗,在全脑照射总剂量(DT)30～40 Gy后,后程缩野对脑转移癌局部病灶行3D-CRT,每次2 Gy,每周5次,加量DT 10～24 Gy,至DT 50～64Gy.观察组在放疗2～4周期间给予紫杉醇65～85 mg/m2,静脉滴注第1、8天,同步化疗,然后继续用紫杉醇单药化疗2～4个周期(紫杉醇65～85 mg/m2,第1、8、15天静脉滴注);28 d为1周期,治疗2月后,观察两组近期疗效、不良反应及评价生活质量;随访2年评价客观疗效和生存率.结果 观察组有效率76.9%,高于对照组45.8%,两组比较有统计学差异(x2=5.120,P＜0.05).Karnofsky计分提高+稳定者观察组80.8%、对照组54.2%,观察组生活质量改善高于对照组(x2=4.059,P＜0.05);与对照组相比,观察组白细胞下降,差异有统计学意义;血小板减少、恶心呕吐、肝功能异常等不良反应发生率稍高于对照组,差异无统计学意义.两组2年生存率比较差异有统计学意义(x2=4.7260,P＜0.05).结论 后程3D-CRT联合紫杉醇单药化疗治疗老年乳腺癌伴脑转移癌患者可提高远、近期疗效,不良反应虽有所增加,但患者能耐受,值得临床上进一步推广应用.

Abstract：

Objective To evaluate the efficacy and adverse reaction of three-dimensional conformal radiation therapy (3D-CRT) combined with chemotherapy of paclitaxel in treatment of brain metastases from breast cancer in the elderly.Methods The 50 patients were randomly divided into observation group (n=26,radiation combined with chemotherapy) and control group (n= 24,simple radiation).In the early stage,both groups received common two-dimesional conformal radiation therapy.The total dose (DT) of whole brain irradiation was 30-40 Gy.In the later stage,the reduced field for the local lesion of brain metastases would be altered to 3D-CRT for the post period with 2 Gy 5 times a week.DT was added from 10-24 Gy up to total DT of 50-64 Gy.The patients were given paclitaxel 65-85 mg/m2 by intravenous drip at 1st and 8th day with synchronization of 2-4 weeks,having paclitaxel chemotherapy of 2-4 circle,28 days a circle.After 2 month treatment,the efficacy and adverse effects of the two groups were observed.follow up for 2 years,the long-term efficacy and survival rate were evaluated.Results The effective rate was 76.9% in observation group and 45.8% in control group,respectively (x2 =5.120,P＜0.05) and the KPS score was 80.8% and 54.2%,respectively.The quality of life was improved in observation group versus control group (x2 =4.059,P＜0.05).Compared with control group,hypoleukemia was significant in observation group (P＜0.05).The complications such as nausea and vomiting,hepatic dysfunction were more in observation group than in control group,but there was no statistical significance between two groups.There was statistic ally significant difference in 2-year survival rate between two groups (x2= 4.7260,P＜0.05).Conclusions The 3D-CRT combined with paclitaxel chemotherapy is a prefered choice for locally advanced brain metastases from breast cancer.More side effects and adverse reaction are observed in observation group.However,all the patients could tolerate them.It is worthy of popularization and application.     

Carbohydrate antigen 125, carbohydrate antigen 15–3 and low-density lipoprotein as risk factors for intraocular metastases in postmenopausal breast cancer

The prognosis of patients with postmenopausal breast cancer (PBC) could be improved by the early detection of intraocular metastases (IOMs). However, serum biomarkers for IOMs in PBC remain elusive. In the current study, we investigated patients with PBC, and compared serum parameters in an IOM and a non-IOM group, and then differentiated the risk factors related to IOMs. A comparison between an IOM and a non-IOM (NIOM) group was performed using Student t-test and a Chi-Squared test. After constructing a Poisson regression model to identify risk factors, we plotted receiver operating characteristic curves to evaluate the predictive value of significant risk factors in detecting IOMs. The incidence of IOMs in PBC was 1.16%. The histopathology results were not significantly different between the 2 groups. The levels of serum carbohydrate antigen 125 (CA-125), carbohydrate antigen 15–3 (CA15–3) and alkaline phosphatase were significantly elevated in IOMs compared with NIOMs (P = .082, P < .001, and P < .001, respectively). Compared with NIOMs, age, carbohydrate antigen 19 to 9, hemoglobin, calcium, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A1 were remarkably lower in IOMs (P = .038, P < .001, P < .001, P = .032, P = .041, P < .001, and P = .001, respectively). Poisson regression suggested that CA-125, CA15–3 and LDL were contributing to IOMs in PBC as risk factors (OR = 1.003, 95% CI: 1.001–1.005; OR = 1.025, 95% CI: 1.019–1.033; OR = 0.238, 95% CI: 0.112–0.505, respectively). A receiver operating characteristic curve revealed that the cut-off values for CA-125, CA15–3 and LDL were 16.78 0 U/mL, 63.175 U/mL, and 2.415 mmol/L, respectively. The combination of CA-125 and CA15–3 showed significant diagnostic value (area under the curve [AUC] = 0.982, P < .001). Our investigation suggests that CA-125, CA15–3 and LDL remarkably predict IOMs in PBC as risk factors, and the combination of CA-125 and CA15–3 shows considerable diagnostic value.     

Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition

We have designed MI-219 as a potent, highly selective and orally active small-molecule inhibitor of the MDM2-p53 interaction. MI-219 binds to human MDM2 with a K(i) value of 5 nM and is 10,000-fold selective for MDM2 over MDMX. It disrupts the MDM2-p53 interaction and activates the p53 pathway in cells with wild-type p53, which leads to induction of cell cycle arrest in all cells and selective apoptosis in tumor cells. MI-219 stimulates rapid but transient p53 activation in established tumor xenograft tissues, resulting in inhibition of cell proliferation, induction of apoptosis, and complete tumor growth inhibition. MI-219 activates p53 in normal tissues with minimal p53 accumulation and is not toxic to animals. MI-219 warrants clinical investigation as a new agent for cancer treatment.     

乳腺癌组织p16基因甲基化与ER、PR、HER2及p53表达的关系

目的探讨乳腺癌组织中p16基因甲基化与相关受体表达的相关性,进一步提高乳腺癌的诊断水平。方法采用甲基化特异性PCR（MSP）法检测86份乳腺癌组织及40份乳腺癌患者血清中p16基因的甲基化状态;采用免疫组化sP法检测乳腺癌组织中雌激素受体（ER）和孕激素受体（PR）、人类表皮生长因子受体2（HER2）及p53基因表达,分析各指标之间及与乳腺癌之间的关系。结果乳腺癌组织及血清中p16基因甲基化率分别为29．1％、27．5％;15例ER、PR、HER2均为阴性表达者（三阴乳腺癌）,p16基因甲基化率为86．67％（13／16）,非三阴乳腺癌71例,p16基因甲基化率为16．9％（12／71）,P〈0．01。p16基因甲基化与ER、PR蛋白表达呈负相关（r=-0．425、-0．512,P均〈0．05）,与HER2表达呈正相关（r=0．443,P〈0．05）;与p53表达无明显相关性。结论p16基因甲基化是乳腺癌中常见的分子改变,其与ER、PR、HER2联合检测可作为乳腺癌早期诊治及预后判断的重要指标。     

Impact of genetic dynamics and single-cell heterogeneity on development of nonstandard personalized medicine strategies for cancer

Cancers are heterogeneous and genetically unstable. Current practice of personalized medicine tailors therapy to heterogeneity between cancers of the same organ type. However, it does not yet systematically address heterogeneity at the single-cell level within a single individual's cancer or the dynamic nature of cancer due to genetic and epigenetic change as well as transient functional changes. We have developed a mathematical model of personalized cancer therapy incorporating genetic evolutionary dynamics and single-cell heterogeneity, and have examined simulated clinical outcomes. Analyses of an illustrative case and a virtual clinical trial of over 3 million evaluable "patients" demonstrate that augmented (and sometimes counterintuitive) nonstandard personalized medicine strategies may lead to superior patient outcomes compared with the current personalized medicine approach. Current personalized medicine matches therapy to a tumor molecular profile at diagnosis and at tumor relapse or progression, generally focusing on the average, static, and current properties of the sample. Nonstandard strategies also consider minor subclones, dynamics, and predicted future tumor states. Our methods allow systematic study and evaluation of nonstandard personalized medicine strategies. These findings may, in turn, suggest global adjustments and enhancements to translational oncology research paradigms.     

Vasoactive intestinal peptide (VIP) induces transactivation of EGFR and HER2 in human breast cancer cells

We analyzed the cross-talk between receptors for vasoactive intestinal peptide (VIP) and the human epidermal growth factor family of tyrosine kinase receptors (HER) in oestrogen-dependent (T47D) and oestrogen-independent (MDA-MB-468) human breast cancer cells. VIP treatment slowly increased the expression levels of EGFR but it rapidly augmented phosphorylation of EGFR and HER2 in both cell lines. This pattern of HERs transactivation was blocked by the specific VIP antagonist JV-1-53, supporting the direct involvement of VIP receptors in formation of P-EGFR and P-HER2. VIP-induced transactivation was also abolished by H89 (protein kinase A inhibitor), PP2 (Src inhibitor) or TAPI-1 (inhibitor of matrix metalloproteases), following a differential pattern. These results shed a new light on the specific signalling pathways involved in EGFR/HER2 transactivation by VPAC receptors and suggest the potential usefulness of VIP receptor antagonists together with current antibodies against EGFR/HER2 and/or tyrosine kinase inhibitors for breast cancer therapy.     

北京市房山区2型糖尿病患者心理性胰岛素抵抗现状调查

目的了解北京市房山区2型糖尿病（T2DM）患者心理性胰岛素抵抗的现状并分析其相关因素。方法采用问卷调查法调查96例T2DM患者,并对相关因素进行Logistic回归分析。结果愿意接受胰岛素治疗的患者占被调查人数的72．9％,不愿意接受胰岛素治疗的占27．1％。多元Logistic回归分析发现,对胰岛素的知晓情况与是否接受胰岛素治疗密切相关（OR=1．814,P〈0．01）。结论房山区T2DM患者心理性胰岛素抵抗的根本因素为胰岛素知识缺乏,应强化糖尿病知识的健康教育。     

6 versus 12 months of adjuvant trastuzumab in HER2+ early breast cancer: A systematic review and meta-analysis

Background:Adjuvant trastuzumab improves survival outcomes of human epidermal receptor 2 positive early breast cancer patients. Currently, administration of 12 months adjuvant trastuzumab is the standard therapy. However, whether 6 months treatment is non-inferior to the standard 12 months treatment remains controversial.Methods:Relevant records were searched in PubMed, Cochrane Library, Web of Science, and EMBASE through Jan 14, 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were meta-analyzed. The primary endpoint was DFS with a non-inferiority hazard margin of 1.2 and the second was OS with 1.43.Results:Three randomized clinical studies met the inclusion criteria, including 3974 patients in 6 months group and 3976 in 12 months group. HR for DFS was 1.18 (95% CI 0.97–1.44, P = .09), with the non-inferiority margin comprised in the 95% CI. HR for OS was 1.14 (95% CI 0.98–1.32, P= .08), whereas the upper limit of 95% CI did not exceed the non-inferiority hazard margin.Conclusion:Our analysis failed to show that 6 months treatment was non-inferior to 12 months treatment in improving the DFS. Although the non-inferiority of the 6-month adjuvant trastuzumab treatment was found for OS, considering that breast cancer patients should receive additional systematic therapies when disease progression or relapse happens, we suggest that 12 months adjuvant trastuzumab treatment should remain the standard therapeutic strategy for patients with early human epidermal receptor 2 positive breast cancer.     

慢性乙型肝炎治疗进展及新策略

近年来由于直接抗病毒药物的问世,慢性乙型肝炎的治疗状况得到明显改善。随着治疗上出现的问题,诸如治疗不佳、耐药等问题,抗病毒治疗的适应证、初选治疗方案以及临床治疗终点探索得到一定的补充和修正。此外,一些新的治疗药物也从不同治疗机制的角度陆续在研制。本文就目前慢性乙型肝炎的治疗进展和新策略进行综述。