Role of receptor tyrosine kinases in gastric cancer： New targets for a selective therapy

Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor family participate in several steps of tumor formation including proliferation and metastatic spread. Several known RTKs are upregulated in gastric cancer being prime targets of a tailored therapy. Only preliminary data exist, however, on the use of the currently clinically available drugs such as trastuzumab, cetuximab, bevacizumab, gefitinib, erlotinib, and imatinib in the setting of gastric cancer. Preclinical data suggest a potential benefit of their use, especially in combination with "conventional" cytostatic therapy. This review summarizes the current knowledge about their use in cancer therapy as well as new approaches and drugs to optimize treatment success.     

Role of chemotherapy and novel biological agents in the treatment of elderly patients with colorectal cancer

Patients older than 65 years are the fastest growing segment of the cancer population. It is estimated that within 20 years over 75% of cases and 85% of deaths from colorectal cancer （CRC） will be in this setting. Concerns about cancer treatment in the elderly relate to comorbidities, which increase proportionally with age, physiological changes associated with aging which may influence drug metabolism and toxicity, and diminishing life expectancy, which particularly impacts decisions surrounding the benefits of adjuvant therapies. Over the last 10 years, significant improvements in the treatment of advanced CRC with combination therapy have been made. The randomized trials which have defined these improvements did not exclude elderly patients. However, the median age of patients in these trials has generally been approximately 60 years. Thus, it appears that some degree of selection is involved with younger and presumably fitter patients being the subjects in most of the pivotal trials. The availability of new molecularly targeted agents and newly improved existing agents has expanded the range of treatment options available. This variety gives greater flexibility in dealing with different subsets of patients, such as the elderly. However, some fit elderly patients seem to tolerate combination therapy reasonably well, while studies on unfit elderly subjects are needed.     

替加环素治疗重症肺炎不良反应分析

目的探讨替加环素治疗重症肺炎患者的不良反应和超说明书剂量用药对不良反应的影响。 方法选择南京医科大学第一附属医院呼吸重症监护病房(RICU)2016年7月至2018年6月使用替加环素治疗的患者，根据替加环素用量分为推荐剂量组和超剂量组，收集两组患者的一般资料、临床特征以及实验室检查，进行分析统计。 结果纳入患者100例，整体观察发现31(31.00%)例出现不良反应，其中皮疹1例，消化系统不适9例，肝功能损伤10例，药物性血小板减少10例，肝功能损伤合并血小板减少1例。推荐剂量组和超剂量组比较，FIB血浆浓度差异有统计学意义(P<0.05)，其余不良反应分析差异无统计学意义。在替加环素联合1种或2种抗菌药物共用时，不良反应发生率别为30.77%(24/78例次)和40.00%(8/20例次)，组间比较差异无统计学意义(P>0.05)。替加环素用药前后比较发现，凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)和凝血酶时间(TT)延长，纤维蛋白原(FIB)降低，尿素氮(BUN)升高，用药前后组间比较差异有统计学意义(P<0.05)。 结论替加环素超剂量使用未明显增加不良反应。应用替加环素应关注肝肾功能损伤、血小板降低等不良反应，警惕药物对凝血系统的影响。     

Targeting receptor tyrosine kinases in gastric cancer

Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials.One group of representative targeted oncogenic kinases,the receptor tyrosine kinases(RTKs),has been associated with gastric cancer development.Trastuzumab,an inhibitor of ERBB2,has been approved for the treatment of gastric cancer,although other receptor tyrosine kinases,such as epidermal growth factor receptor,vascular endothelial growth factor,platelet-derived growth factor receptor,c-Met,IGF-1R and fibroblast growth factor receptor 2,are also activated in gastric cancer.The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients.On the other hand,the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients;however,a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial.Other clinical trials,especially phaseⅢtrials that have tested drugs targeting RTKs,such as cetuximab,panitumumab,gefitinib,erlotinib,figitumumab,sorafenib,sunitinib and lapatinib,have shown that these drugs have modest effects against gastric cancer.This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies.     

用力肺功能检查的不良反应观察及安全性探讨

目的 观察用力肺功能检查的不良反应及探讨其安全性.方法 采用问卷调查方式对996例行用力肺功能检查的受试者进行不良反应评价.调查内容主要包括:不良反应的症状、程度、处理措施和恢复情况.结果 270例(27.1％)出现了294个不良反应,其中有24例受试者同时出现2～3个不良反应.以呼吸症状发生率最高,其次为神经肌肉和咽喉部症状,其中呼吸困难129例,咳嗽79例,头晕43例,发生率分别为13.0％、7.9％、4.3％.气道阻塞组的呼吸困难发生率为33.4％,显著高于无气道阻塞组(P=0.000),并随着通气障碍的程度加重,呼吸困难的发生率逐渐增高,以极重度组发生率最高,达75.4％.轻度和中度不良反应分别占81.0％和19.0％,无重度不良反应.结论 用力肺功能检查可引起不良反应的出现,但只要临床上应严格掌握检查指征,及时恰当地处理不良反应,用力肺功能检查是安全的.     

Three ileus cases associated with the use of dipeptidyl peptidase‐4 inhibitors in diabetic patients

Dipeptidyl peptidase (DPP)‐4 inhibitors are a new class of antidiabetic drugs that increase incretin hormone levels to enhance blood sugar level‐dependent insulinotropic effects, suppress glucagon action, and reduce bowel motility. These incretin effects are ideal for blood sugar control. However, the safety profile of DPP‐4 inhibitors is not yet established. Herein, we present three cases of ileus, considered to be closely related to the use of DPP‐4 inhibitors, in diabetic patients. Each of the three patients exhibited some risk of a deficiency in bowel movement; the onset of ileus was within 40 days after strengthened inhibition of DPP‐4. The use of a DPP‐4 inhibitor could be safe, although the cases presented herein enable us to inform the scientific community to some of the potential adverse effects of the use of DPP‐4 inhibitors in select populations.     

Clinical features of adverse reactions associated with telbivudine

AIM： To analyze the clinical features and risk factors of adverse reactions associated with telbivudine.
METHODS： Clinical data were collected from cases that presented with serious adverse reactions to telbivudine. We analyzed general information and medicine status, clinical features, results of examination, and misdiagnosis.
RESULTS： Out of 105 patients who were treated with telbivudine for hepatitis B in an outpatient department from January, 2007 to January, 2008, five presented with serious adverse drug reactions. Most of these five patients had used other nucleoside analogues in the past. Four were treated with a combination of telbivudine and interferon or another nucleoside analogue, while the other received an increased dose of telbivudine. The main adverse reactions were myalgia and general weakness. This was accompanied by cardiac arrhythmia in one patient, and nervous symptoms in three. Serum creatine kinase was elevated. The rate of misdiagnosis was high.
CONCLUSION： The adverse reactions were related to telbivudine, but the biological mechanism of the reactions is not yet clear. Combination therapy with interferon or another nucleoside analogue and a high dose may increase the risk of adverse reactions.     

KRAS突变对抗EGFR单抗治疗转移性结直肠癌影响的Meta分析

目的评价化疗或联合抗EGFR单抗治疗转移性结直肠癌的临床疗效与KRAS基因突变的关系。方法用"colorectal carcinoma"、"cetuximab"、"Panitumumab"系统检索PubMed、EMBASE、Ovid、CENTRAL(2000年1月-2011年11月)中关于KRAS突变对化疗或联合抗EGFR单抗(包括Cetuximab和Panitumumab)治疗转移性结直肠癌疗效的影响。结果包括无进展期(progressionfree survival,PFS)和总生存期(overall survival,OS)及其相应HR,依据Cochrane Handbook 5.0.2对符合标准的RCT进行Meta分析。结果 PFS的HR在KRAS野生型患者和突变型患者分别为-0.22(95%CI:-0.37~-0.07,P=0.005)和1.07(95%CI:0.88~1.30,P=0.48),OS的HR在KRAS野生型和突变型则为0.83(95%CI:0.82~0.85,P0.00001)、1.04(95%CI:0.95~1.15,P=0.40)。抗EGFR治疗均未见明显延长KRAS突变型mCRC患者的PFS和OS。结论 KRAS状态是预测mCRC患者抗EGFR治疗疗效的有效生物学标志之一。     

Anti-epidermal growth factor receptor monoclonal antibodies in metastatic colorectal cancer: A meta-analysis

AIM: To investigate the correlation between Kirsten rat sarcoma viral oncogene homolog(KRAS) status and the therapeutic effects of anti-epidermal growth factor receptor(EGFR) monoclonal antibodies(Mo Abs) in metastatic colorectal cancer(m CRC).METHODS: Randomized controlled trials(RCTs) were identified and the association between KRAS mutation and clinical outcome in m CRC patients treated with anti-EGFR Mo Abs was investigated. Ten RCTs wereincluded in this meta-analysis. Progression-free survival and overall survival were used to assess the strength of the relationship between KRAS mutation and clinical outcome.RESULTS: In first-line treatment, survival benefit was confined to patients with wild-type KRAS. Chemotherapy regimens and angiogenesis inhibitor treatment influenced the results of the analysis. Wildtype KRAS m CRC patients did not seem to benefit from oxaliplatin-based chemotherapy(PFS: HR = 0.88, 95%CI: 0.70-1.10; OS: HR = 0.93, 95%CI: 0.82-1.04). Clinical benefit in m CRC patients was limited to therapeutic regimens which included anti-EGFR Mo Abs and fluorouracil-based therapy(PFS: HR = 0.77, 95%CI: 0.69-0.86; OS: HR = 0.85, 95%CI: 0.75-0.95). When anti-EGFR Mo Abs were used as second- or further-line treatment, clinical benefit was still confined to patients with wild-type KRAS. CONCLUSION: KRAS status is a potential predictive marker of clinical benefit due to anti-EGFR Mo Ab therapy in m CRC patients.     

1031例患者应用去甲万古霉素不良反应观察

目的　评价注射用去甲万古霉素的安全性 ,为临床安全有效地使用该药提供依据。方法　观察去甲万古霉素静脉用药的住院患者在用药期间发生的任何不良事件 ,判断不良事件与药物的关系并计算不良反应发生率。结果　 2 0 0 2年 3月～ 2 0 0 3年 6月共入选病例 10 31例 ,其中可进行临床和实验室安全性评价者共 96 5例。 96 5例中出现不良反应者共 80例 ,不良反应发生率为8 2 9%。各系统不良反应发生频率按高低依次为肾功能损害 ( 4 0 4 % )、肝功能损害 ( 2 38% )和过敏反应 ( 1 76 % )。合并应用其他抗感染药物及年龄≥ 6 0岁患者中去甲万古霉素总不良反应发生率较高 ,年龄≥ 6 0岁人群中肾功能损害发生率较 <6 0岁患者为高 ,疗程≥ 14d时肝功能损害发生率较<14d者为高 ,均为独立危险因素 (P <0 0 5 )。结论　注射用去甲万古霉素在临床应用中不良反应发生率较低 ,少数患者可出现肾、肝功能损害等不良反应 ,其程度多较轻微 ,可耐受。老年、疗程≥ 2周及合并应用其他抗感染药物者易发生不良反应     

肺结核合并糖尿病临床治疗观察

目的观察肺结核并发糖尿病血糖控制对痰菌阴转及空洞愈合的影响。方法131例均采用2SHRZ(E)/4HR,观察组68例根据血糖控制情况分为1组控制理想2组控制较好3组控制不良与对照组63例无合并症的菌阳肺结核对照。结果满疗程治疗后痰菌阴转:1组与2组,1组与对照组,比较差别无显著性。1组与3组比较差别有显著性,空洞改变情况:1组与对照组比较差别无显著性,1组与3组比较差别有显著性。结论肺结核并发糖尿病血糖控制稳定与否极为关键,血糖控制良好,肺结核病可在短程化疗期间取得很好疗效。     

Targeted therapy in first line treatment of RAS wild type colorectal cancer

The debate on the optimal drug combination for treating chemotherapy-nave patients with metastatic colorectal cancer has recently become particularly heated.The present editorial will review recent data on this topic.The FIRE-3 and PEAK trials have shown a 7.5 to 12 mo survival advantage with the use anti-epidermal growth factor receptor(anti-EGFR)antibodies.The CALGB 80405 has shown no difference between anti-EGFR and anti-vascular endothelial growth factor agents.All three trials have consistently shown a significant increase in objective response rate.These data suggest that there is a subset of metastatic colorectal cancer patients,rigorously selected by molecular profiling,who particularly benefit from an anti-EGFR-based regimen in the first-line setting.     

2种化疗方案治疗老年初治肺结核的疗效和安全性研究

目的比较2种结核化疗方案治疗老年初治肺结核的疗效及安全性。方法将符合纳入标准的130例老年初治涂阳肺结核患者随机分为试验组和对照组。试验组给予2HLEV/4HL治疗,对照组给予2HRZE/4HR治疗,比较2组疗效和安全性。结果化疗2月和6月末,试验组和对照组痰菌阴转率差异均无统计学意义;化疗6个月疗程结束时病灶变化(显吸、吸收、不变或恶化)和空洞变化(闭合、缩小、不变或增大)组间差异均无统计学意义。试验组不良反应发生率是28.3%,小于对照组的57.9%(P=0.001);2组不良反应均以胃肠道反应和肝损伤最多见,试验组胃肠道反应、肝损伤及高尿酸血症发生率均小于对照组(P均0.05)。结论 2种结核化疗方案疗效无差异,但2HLEV/4HL的不良反应发生率低,对老年初治肺结核患者是更安全的化疗方案。     

晚期肺癌合并慢阻肺化疗后肺部感染的病原谱及耐药性分析

目的探讨合并慢性阻塞性肺疾病(简称慢阻肺)的晚期肺癌患者化疗后肺部感染的病原菌分布及其耐药情况,指导临床合理用药。方法选择2011年1月至2014年5月徐州医学院附属医院呼吸科收治的65例化疗后肺部感染的晚期肺癌合并慢阻肺患者为研究对象,对所有患者痰标本中分离出的病原菌进行菌种鉴定和耐药性分析。结果共分离出103株病原菌,其中革兰阴性杆菌79株,占76.6%;革兰阳球性菌8株,占7.8%;真菌16株,占15.6%。最主要的革兰阴性杆菌依次为大肠埃希氏菌(28.2%)、铜绿假单胞菌(15.5%)、肺炎克雷伯菌(13.6%)、鲍曼不动杆菌(8.7%)、阴沟肠杆菌(5.8%)。大肠埃希氏菌、肺炎克雷伯杆菌和铜绿假单胞菌对对亚胺培南、头孢哌酮/舒巴坦、哌拉西林/他唑巴坦、阿米卡星敏感性较高。鲍曼不动杆菌对碳青霉烯类药物耐药率高(55.6%),对头孢哌酮舒巴坦和哌拉西林他唑巴坦敏感性相对较好。金黄色葡萄球菌未发现对万古霉素耐药。结论合并慢阻肺的晚期肺癌化疗后肺部感染致病菌以革兰阴性杆菌为主;其次为真菌、革兰氏阳性球菌。细菌耐药情况较为严重,应结合本地区病原菌分布特点及耐药状况,合理选用抗菌药物。     

肺癌患者肺叶切除术后肺功能的变化

目的观察肺癌患者行单侧肺叶切除术的术前、术后肺功能及血气指标变化。方法测定63例行单侧肺叶切除术的肺癌患者术前、术后3个月的肺功能及血气指标。结果术后早期肺功能各项指标均有下降（P〈0．05）。术后3个月FEV1及DLCO较术前有所改善,与术前相比,P〈0．05。结论单侧肺叶切除术对肺癌患者肺功能无显著影响,其气道阻塞程度及弥散功能术后有所改善。     

Computerized tomographic finding of saddle pulmonary embolism is associated with high mortality in cancer patients

Background: Large pulmonary embolism (PE) is associated with high mortality in cancer patients. Several risk stratification methods have been used in PE setting. While computer‐assisted tomography (CT) is now the preferred diagnostic modality for PE, its prognostic value is not well established. Methods: A retrospective study of patients discharged from our centre between 2000 and 2006 with a PE diagnosis identified 52 patients with thrombus in the main pulmonary artery or the right or left branch. Clinical, echocardiographic and CT data were reviewed; vital status was determined 1 month and 1 year after index event. Patients were divided into saddle (defined as main pulmonary artery thrombus) and non‐saddle PE. Multivariate logistic regression was applied to predict vital status, with patient age and CT parameters as predictors. Results: Eighteen out of 52 patients were found to have a saddle PE. No significant difference was found between the group characteristics, although saddle PE patients were more likely to receive thrombolytic therapy (27.8% vs 2.9%, P = 0.02) and have an echocardiogram within 30 days of PE (61.1% vs 29.4%, P = 0.03). Overall mortality at 1 month was 9.6% with no difference between groups. At 1 year, mortality rates in saddle PE were significantly higher (83.3% vs 41.2%, P = 0.004). Presence of saddle PE was associated with an odds ratio of death within 1 year of 7.41 (95% confidence interval: 1.75–31.46, P = 0.007). Conclusion: The relatively simple distinction of saddle versus non‐saddle PE by CT findings may provide a straightforward method for risk stratification, and remains useful up to 1 year after the index event.