Ranked importance of outcomes of first-line versus repeated chemotherapy among ovarian cancer patients

Purpose  

To examine the importance of possible outcomes of first-line versus repeated chemotherapy to ovarian cancer patients and to compare doctors' treatment intentions with patients' beliefs about cure.     

KRAS mutations as essential promoters of lymphangiogenesis via extracellular vesicles in pancreatic cancer

Kirsten rat sarcoma virus (KRAS) gene mutations are present in more than 90% of pancreatic ductal adenocarcinomas (PDACs). KRAS^G12D is the most frequent alteration, promoting preneoplastic lesions and associating with a more aggressive phenotype. These tumors possess increased intratumoral lymphatic networks and frequent lymph node (LN) metastases. In this issue of the JCI, Luo, Li, et al. explored the relationship between the presence of the KRAS^G12D mutation and lymphangiogenesis in PDAC. The authors used in vitro and in vivo models and an elegant mechanistic approach to describe an alternative pathway for lymphangiogenesis promotion. KRAS^G12D induced SUMOylation of heterogenous nuclear ribonucleoprotein A1 (hnRNPA1) via SAE1 and SUMO2 activation. SUMOylated hnRNPA1 was loaded into extracellular vesicles (EVs) and internalized by human endothelial lymphatic cells (HLEC). Further, SUMOylated hnRNPA1 promoted lymphangiogenesis and LN metastasis by stabilizing prospero homeodomain protein 1 (PROX1) mRNA. These data provide mechanistic insight into cancer lymphangiogenesis with the potential for developing biomarkers and RAS pathway therapeutics.     

谷胱甘肽-S-转移酶P1基因多态性与晚期胃癌患者对顺铂化疗疗效的相关性研究

目的 基因多态性通过影响药物的代谢、转运和作用靶点从而导致药物疗效和毒性的个体差异,寻找明确的生物学标记来识别获益人群已成为最大的挑战.本研究旨在观察谷胱甘肽-S-转移酶P1(GSTP1)基因多态性与以顺铂(DDP)为基础的化疗方案治疗晚期胃癌疗效间的关系.方法 收集经病理学确诊的晚期胃癌患者59 例.所有病例化疗前抽取外周静脉血,提取脱氧核糖核酸(DNA),用连接酶检测反应技术(PCR-LDR)检测研究对象的GSTP1 基因型.所有患者经多西他赛(DOCETAXEL)/DDP/5-氟尿嘧啶(5-FU) 联合方案化疗,化疗结束后观察疗效及其与GSTP1 基因多态性的关系.结果 59 例晚期胃癌患者中,15 例(25.4%)为GSTP1 G/G 基因型,21 例(35.6%)为GSTP1 G/A 基因型,23 例(39.0%)为GSTP1 A/A 基因型.其中4 例完全缓解,14 例部分缓解,19 例稳定,22 例进展,总有效率为30.5%(18/59).GSTP1 G/G 基因型患者的化疗有效率(73.3%)明显高于G/A 基因型患者(19.0%)(χ2 ＝10.616,P ＝0.005),同样明显高于A/A 基因型患者(13.0%)(χ2 ＝14.202,P ＝0.001).G/A 基因型患者的化疗有效率与A/A 基因型患者之间差异无统计学意义(χ2 ＝0.31,P＝0.856).突变基因型(G/G +G/A)对化疗较敏感,其化疗有效率是野生基因型(A/A)的3.2 倍(95% CI 1.442 ～7.302,P ＝0.004).结论 GSTP1 基因型对预测以DDP 为基础化疗方案治疗晚期胃癌的疗效具有较好的临床意义.     

运用高灵敏度COLD-PCR法检测胰腺癌和结直肠癌患者KRAS基因突变

目的 评价COLD-PCR法检测胰腺癌和结直肠癌患者KRAS基因突变的价值.方法 采用COLD-PCR/Sanger测序法与普通PCR/Sanger测序法检测KRAS基因野生型结直肠癌细胞系SW116中混有的KRAS基因突变型和结直肠癌细胞系SW480中的KR4S基因突变,确定两种方法 的灵敏度,并采用两种方法 分别检测20例胰腺癌和39例结直肠癌患者石蜡包埋组织的KRAS基因突变,并评价两种方法 的符合率.结果 细胞系检测结果 显示,普通PCR/Sanger测序法和COLD-PCR/Sanger测序法检测KRAS基因突变的灵敏度分别为1∶20和1∶100(突变型:野生型).COLD-PCR/Sanger法检测20例胰腺癌患者KRAS基因突变率[75%(15/20)]高于普通PCR/Sanger测序法[40%(8/20),x2=5.013,P<0.05];COLD-PCR/Sanger测序法检测39例结直肠癌患者的KRAS基因突变率[44%(17/39)]高于普通PCR/Sanger测序法[31%(12/39),x2=1. 372,P=0.174)].两种方法 检测胰腺癌标本的符合率为65%,但一致性较差(Kappa=0.364,P<0.05);而两种方法 检测结直肠癌标本的符合率为87%,且一致性较好(Kappa=0.730,P<0.05).结论 COLD-PCR/Sanger测序法是一种高灵敏性检测胰腺癌和结直肠癌患者KRAS基因突变的方法 .     

Impact of oral mucositis on short-term clinical outcomes in paediatric and adolescent patients undergoing chemotherapy

Purpose

The purpose of this study is to determine the burden of the peak severity of oral mucositis and severity over time on selected clinical outcomes in paediatric and adolescent patients receiving chemotherapy.

Patients and methods

A multicentre study enrolled 140 patients between the ages of 6 and 18 years, who had been treated with chemotherapy and completed the self-report Mouth and Throat Soreness-related questions of the Oral Mucositis Daily Questionnaire for 14 days. Clinical data were collected from patients' medical records during the first 14 days after starting chemotherapy.

Results

Forty-one percent developed oral mucositis. Multiple linear regression analysis revealed that oral mucositis was significantly associated with an increased loss of baseline body weight, after controlling for nausea/vomiting (β?=?0.34, p?=?0.002). Multiple logistic regression analysis showed that severe mucositis was significantly associated with a higher probability of fluid replacement, after controlling for nausea/vomiting (adjusted OR?=?12.8; 95 % CI?=?2.7–61.0; p?=?0.001). In addition, severe mucositis was significantly associated with a higher probability of fever, after controlling for neutropoenia (adjusted OR?=?5.4; 95 % CI?=?1.8–15.4; p?=?0.002). No difference was observed for oral or systemic infections among the subgroups. About 5 % of the patients with oral mucositis had delays in chemotherapy (≤7 days). None of the patients had dose modification or unplanned hospitalization due to oral mucositis. The associations of peak severity and overall oral mucositis with adverse clinical outcomes in paediatric and adolescent patients were equivalent.

Conclusion

Oral mucositis is associated with negative effects on clinical outcomes.     

Impact of telehealth on clinical outcomes in patients with heart failure

The purpose of this randomized field study was to determine the effects of telehomecare on hospitalization, emergency department (ED) use, mortality, and symptoms related to sodium and fluid intake, medication use, and physical activity. The sample consists of 284 patients with heart failure. The authors used logistic regression to study the effects of telehomecare on health services utilization and mortality and a general linear model to analyze changes in self-reported symptoms. On average, patients in the telehomecare groups had a lower probability of hospitalizations and ED visits than did patients in the control group. Differences were statistically significant at 60 days but not 120 days. Results show a greater reduction in symptoms for patients using telehomecare compared to control patients. The technology enables frequent monitoring of clinical indices and permits the home health care nurse to detect changes in cardiac status and intervene when necessary.     

胰腺癌中EGFR、KRAS、BRAF基因突变状况分析及意义

目的:检测胰腺癌组织EGFR、KRAS、BRAF基因突变状况,为胰腺癌EGFR靶向治疗研究奠定基础.方法:提取胰腺癌及胰腺良性病变石蜡组织切片中基因组DNA,PCR扩增EGFR 18、19、21外显子片段,KRAS2、3外显子片段,BRAF15外显子片段,采用直接测序法检测其突变状况.结果:32例胰腺癌患者中有24例患者存在KRAS基因突变,10例良性病变组织均未发现突变,两者差异具有统计学意义(x2=14.57,P=1.35× 10-4),其中22例12密码子突变(G12D14例,G12V8例);2例61密码子突变(Q61L).所有检测样本中未见BRAF突变.共3例EGFR突变,其中包括1例19外显子突变(de1746-750),2例21外显子突变(L858R),10例良性病变组织未见突变.结论:在胰腺癌中KRAS基因突变可能为EGFR通路失调的主要原因,其次是EGFR突变,BRAF突变未见.     

Periodontal infection in cancer patients treated with high-dose chemotherapy

The infected and inflamed periodontium can act as a focus for systemic infection in neutropenic cancer patients. The incidence of these oral infections is unknown, but probably underestimated. Periodontal infections can easily be overlooked, primarily because symptoms of gingival inflammation may be minimal and the infection may be located in deeper parts of the periodontium. Assessment of a patient's periodontal condition before the onset of profound neutropenia is critical to the diagnosis and the management of these potentially life-threatening infections. This review article is aimed at informing supportive care providers of recent insights into the pathogenesis of periodontal diseases and the role of subgingival microorganisms, with the emphasis on these infections in cancer patients treated with high-dose chemotherapy. Furthermore, a multidisciplinary approach to the management of periodontal infections and the need for future research is discussed.     

吉西他滨联合卡培他滨在转移性胰腺癌一线化疗中的疗效及安全性分析

目的分析研究吉西他滨联合卡培他滨在转移性胰腺癌一线化疗中的疗效及安全性。方法 23例初治转移性胰腺癌一线化疗接受吉西他滨联合卡培他滨:吉西他滨1000 mg/m2,静脉滴注30 min,第1、8天;卡培他滨650 mg/m2,2次/天,口服,第1~14天;每3周1个疗程,评价它的总生存、无进展生存、客观缓解率、临床获益率、临床获益反应、糖类抗原19-9(CA19-9)缓解率和不良反应等。结果 23例转移性胰腺癌患者中,4例出现部分缓解,6例获得疾病稳定,13例出现按肿瘤进展,总客观缓解率为17.4%,平均缓解持续时间为6.8个月,临床获益为43.5%,临床获益反应率为52.2%,CA19-9缓解率为65.2%,中位无进展生存为6.1个月,1年无进展生存率14.2%;中位生存时间为7.3个月,1年生存率为25.1%。绝大部分治疗相关不良反应是1至2级,最常见的3/4毒性反应为中性粒细胞减少。结论研究证实吉西他滨与卡培他滨联合方案可成为转移性胰腺癌一线化疗方案之一;同时,临床获益反应在疗效相近的化疗方案的选择上有着重要的指导作用。     

局部晚期宫颈癌患者新辅助化疗疗效观察简

目的 探讨局部晚期宫颈癌患者术前新辅助化疗的疗效.方法 分析55例IB2期宫颈癌经1～2疗程＂伊替立康＋奈达铂＂方案新辅助化疗的患者（实验组）和32例直接行根治性手术的宫颈癌患者（对照组）的临床资料,评价新辅助化疗（NACT）在IB2期宫颈癌治疗中的作用.结果 ＂伊立替康＋奈达铂＂方案化疗不良反应轻,总有效率为89.09%,其中完全缓解（CR）16.36%,部分缓解（PR）72.72%,鳞癌有效率90.0%,腺癌有效率75.0%,新辅助化疗组术后盆腔淋巴结转移为19.0%,明显低于对照组患者（33.8%,P〈0.05）.两组患者宫旁侵润及阴道切缘阳性间差异不具有显著性意义（P〉0.05）,新辅助化疗组3年累积生存率70.12%,明显高于对照组55.26% （P〈0.05）.结论 新辅助化疗治疗局部晚期宫颈癌安全有效,可缩小局部病灶,降低部分患者临床分期,提高手术率,控制盆腔淋巴结转移,并减少化疗并发症或手术并发症的发生.     

High incidence of severe neutropenia after gemcitabine-based chemotherapy in Chinese cancer patients with CDA 79A>C mutation

Cytidine deaminase (CDA) is a crucial enzyme in gemcitabine inactivation. Mutations in CDA gene have been found to influence the activity of CDA enzyme, which might lead to altered pharmacokinetics profile and clinical outcome of gemcitabine. In this study, the screening for the presence of CDA 79A>C and CDA 208G>A was performed by allele-specific PCR and restriction fragment length polymorphism, respectively. No difference in CDA allele frequencies was found between Chinese cancer patients and healthy volunteers. The frequencies for CDA 79A>C and 208G>A in the studied population were 12.2% and 1.0%, respectively. While a high incidence of grade 3-4 neutropenia was noted as 5 out of 8 (62.5%) patients heterozygous or homozygous for CDA 79A>C mutation developed it, in patients homozygous for the wild-type allele, the incidence was only 17.2% (5 out of 29) (p=0.021). Our study suggests that CDA 79A>C mutation might be a potential risk factor of gemcitabine-induced neutropenia toxicity.     

No duplicate KRAS mutation is identified on the same allele in gastric or colorectal cancer cells with multiple KRAS mutations

Codon 12 and 13 mutations in 170 colorectal cancer (CRC) and 66 gastric cancer (GC) specimens were analysed by an 'enriched' polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. All identified mutations were verified by direct sequencing of the second PCR products. Among the 170 CRC specimens, mutations were identified in 47 (28%) and 13 (7.6%) cases in codons 12 and 13, respectively. In the 66 GC specimens examined, however, mutations in codons 12 and 13 were only detected in two (3.0%) and one (1.5%) cases, respectively. Mutations in both codon 12 and 13 were found in 3/170 (1.8%) CRCs and 1/66 (1.5%) GCs. Duplicate mutations were never identified in the same allele, which was confirmed by direct sequencing of the second amplified products. The majority of colorectal and gastric cancer cells with KRAS mutations are homogeneous because they have the same KRAS mutation. A few colorectal or gastric cancers, however, showed heterogeneity, as verified by the fact that single mutations were identified in the same allele.     

Palliation of oral mucositis symptoms in pediatric patients treated with cancer chemotherapy

This prospective randomized 2-period crossover study aimed at comparing the efficacy of 2 oral care protocols differing in the type of mouthwashes: chlorhexidine versus benzydamine in alleviating oral mucositis symptoms for children undergoing chemotherapy. Forty subjects were randomly allocated to receive either chlorhexidine first then benzydamine protocols or benzydamine first then chlorhexidine protocols. Each protocol was started on the first day of chemotherapy and continued for 21 days. Subjects were evaluated in intervals of 3 to 4 days using the World Health Organization (WHO) grading for mucositis and 10-cm visual analogue scale for oral symptoms evaluations. Among 34 evaluable subjects, 26% and 48% of them using chlorhexidine and benzydamine had WHO grade II mucositis, respectively (P < .05). The results revealed a significant difference in mean area under the curve (AUC) of mouth pain (1.35 +/- 2.26 versus 3.09 +/- 3.21) (P = .05), and a trend of a lessening of mean AUC of difficulty in eating/chewing (2.49 +/- 3.74 versus 2.71 +/- 4.1) (P = .82) and swallowing (1.34 +/- 3.31 versus 1.91 +/- 4.03) (P = .53) for subjects receiving chlorhexidine compared to those receiving benzydamine. In conclusion, chlorhexidine may be helpful in palliating mucositis symptoms for children in chemotherapy. The beneficial effect, however, is small and needs to be confirmed in a larger trial.     

整体护理在非小细胞肺癌化疗患者中的应用

目的探讨整体护理在非小细胞肺癌(NSCLC)化疗患者中的应用价值。方法选取2012年2月—2014年4月期间的NSCLC患者50例设为观察组,2010年1月—2012年2月期间的NSCLC患者45例设为对照组。2组均采用NP(长春瑞滨+顺铂)或TP(紫杉醇+顺铂)方案化疗,对照组给予常规护理,观察组给予整体护理。结果观察组有效率(RR)为82.00%,对照组RR为77.78%,2组比较差异无统计学意义(P0.05);2组不良反应发生率差异无统计学意义(P0.05);观察组护理依从率为94.00%,对照组护理依从率为77.78%,2组比较差异有统计学意义(P0.05);观察组护理总满意率98.00%,对照组护理总满意率82.22%,2组比较差异有统计学意义(P0.05);观察组化疗后生活质量评分(FACT-L)中情绪、生活能力、其他因素得分及总分与化疗前差异显著(P0.01),对照组各项评分均显著下降(P0.01),2组差异有统计学意义(P0.01)。结论整体护理可显著改善NSCLC患者化疗后的生活质量,提高护理依从性,值得临床推广。     

化疗联合DC-CIK细胞治疗对胰腺癌患者免疫功能的影响

目的探讨DC-CIK细胞免疫治疗对化疗后胰腺癌患者免疫功能的影响。方法对50例经病理确诊的胰腺癌患者依据治疗方式分为两组:化疗联合自身DC-CIK细胞治疗25例患者作为联合治疗组,同期单纯化疗25例患者作为对照组。分别于治疗前、治疗后相同时间点取外周血,采用流式细胞仪检测T细胞亚群及CD4+CD25+CD127low调节性T细胞(Treg)的变化;ELISA方法检测IFN-γ及IL-4水平的变化。结果联合治疗组患者治疗后外周血CD3+、CD4+、CD3+CD56+T细胞百分率上升,CD4+/CD8+值上调,CD8+T细胞百分率下降(P<0.05或P<0.01);CD4+CD25+CD127lowTreg下降(P<0.01);Th1细胞因子IFN-γ水平较治疗前升高,而Th2细胞因子IL-4水平降低(P<0.01)。对照组单纯化疗后CD3+、CD4+、CD8+细胞百分率下降(P<0.05或P<0.01);CD4+CD25+CD127lowTreg下降(P<0.01);IFN-γ和IL-4水平降低(P均<0.01)。结论化疗联合DC-CIK细胞治疗能提高胰腺癌患者的免疫功能,增强机体的抗肿瘤免疫效应,是治疗胰腺癌患者的辅助手段之一。