Predicting a local recurrence after breast-conserving therapy by gene expression profiling

Introduction

To tailor local treatment in breast cancer patients there is a need for predicting ipsilateral recurrences after breast-conserving therapy. After adequate treatment (excision with free margins and radiotherapy), young age and incompletely excised extensive intraductal component are predictors for local recurrence, but many local recurrences can still not be predicted. Here we have used gene expression profiling by microarray analysis to identify gene expression profiles that can help to predict local recurrence in individual patients.

Methods

By using previously established gene expression profiles with proven value in predicting metastasis-free and overall survival (wound-response signature, 70-gene prognosis profile and hypoxia-induced profile) and training towards an optimal prediction of local recurrences in a training series, we establish a classifier for local recurrence after breast-conserving therapy.

Results

Validation of the different gene lists shows that the wound-response signature is able to separate patients with a high (29%) or low (5%) risk of a local recurrence at 10 years (sensitivity 87.5%, specificity 75%). In multivariable analysis the classifier is an independent predictor for local recurrence.

Conclusion

Our findings indicate that gene expression profiling can identify subgroups of patients at increased risk of developing a local recurrence after breast-conserving therapy.     

Microbiological assessment of indoor air of a teaching hospital in Nigeria

Objective

To investigate the quality of indoor air of different wards and units of Olabisi Onabanjo University Teaching Hospital, Sagamu, to ascertain their contribution to infection rate in the hospital.

Methods

The microbial quality of indoor air of nine wards/units of Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria was conducted. Sedimentation technique using open Petri-dishes containing different culture media was employed and samplings were done twice daily, one in the morning shortly after cleaning and before influx of people/patients into the wards/units and the other in the evening when a lot of activities would have taken place in these wards. Isolates were identified according to standard methods.

Results

Results showed that there was a statistically significant difference (χ² = 6.016 7) in the bacteria population of the different sampling time whereas it was not so for fungi population (χ² = 0.285 7). Male medical ward (MMW) and male surgical general (MSG) recorded the highest bacterial and fungal growth while the operating theatre (OT) was almost free of microbial burden. The bacteria isolates were Staphylococcus aureus, Klebsiella sp., Bacillus cereus, Bacillus subtilis, Streptococcus pyogenes and Serratia marscences while the fungi isolates included Aspergillus flavus, Penicillium sp., Fusarium sp., Candida albicans and Alternaria sp. Staphylococcus aureus was the predominantly isolated bacterium while Penicillium sp. was the most isolated fungus.

Conclusions

Though most of the microbial isolates were potential and or opportunistic pathogens, there was no correlation between the isolates in this study and the surveillance report of nosocomial infection during the period of study, hence the contribution of the indoor air cannot be established. From the reduction noticed in the morning samples, stringent measures such as proper disinfection and regular cleaning, restriction of patient relatives'' movement in and out of the wards/units need to be enforced so as to improve the quality of indoor air of our hospital wards/units.     

难治性根尖周炎的原因分析与疗效观察

目的 分析难治性根尖周炎发生的原因及治疗后的疗效观察.方法 选择172例难治性根尖周炎患牙,针对不同原因分别给予对症治疗,并观察1年后的临床疗效.结果 1年后复查,166例治愈,6例无效,治愈率为96.5%.结论 认真分析寻找难治性根尖周炎的病因,针对不同病因进行治疗,能提高治愈率.     

胃酸抑制剂不会增加老年患者术后肺炎的发病风险

本研究在于确定胃酸抑制剂是否会增加选择性手术患者术后发生肺炎的风险。 此项人群前瞻性队列研究于1992年4月1日-2008年3月31日在加拿大开展。年龄大于65岁已确定进行选择性手术的患者入组。将本年度在手术前服用过两种或以上胃酸抑制剂的患者以及术前90天内服用过至少一种胃酸抑制剂的患者入试验组,     

老年急性结石性胆囊炎手术治疗的临床分析

目的 探讨老年人急性胆囊炎的临床特点和手术治疗经验.方法 选取本院及常州市武进人民医院2009年1月～2012年12月收治的老年急性结石性胆囊炎患者52例,进行手术治疗后的回顾性分析.结果 手术治疗后并发症以水电解质紊乱、肺部感染、肾功能不全、切口裂开、切口感染为常见,共18例（13%）,所有患者都无脏器或胆道损伤.结论 应根据老年人急性胆囊炎特殊的临床特点,及时选择合适的手术时机及手术方式.早期手术可取得良好的治疗效果.     

Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict benefit of intensified carboplatin-based chemotherapy

Introduction

BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating agents and platinum salts. HRD can be caused by BRCA mutations, and by other mechanisms. To identify HRD, studies have focused on triple-negative (TN) breast cancers as these resemble BRCA1-mutated breast cancer closely and might also share this hypersensitivity. However, ways to identify HRD in non-BRCA-mutated, estrogen receptor (ER)-positive breast cancers have remained elusive. The current study provides evidence that genomic patterns resembling BRCA1- or BRCA2-mutated breast cancers can identify breast cancer patients with TN as well as ER-positive, HER2-negative tumors that are sensitive to intensified, DSB-inducing chemotherapy.

Methods

Array comparative genomic hybridization (aCGH) was used to classify breast cancers. Patients with tumors with similar aCGH patterns as BRCA1- and/or BRCA2-mutated breast cancers were defined as having a BRCA-like^CGH status, others as non-BCRA-like^CGH. Stage-III patients (n = 249) had participated in a randomized controlled trial of adjuvant high-dose (HD) cyclophosphamide-thiotepa-carboplatin (CTC) versus 5-fluorouracil-epirubicin-cyclophosphamide (FE₉₀C) chemotherapy.

Results

Among patients with BRCA-like^CGH tumors (81/249, 32%), a significant benefit of HD-CTC compared to FE₉₀C was observed regarding overall survival (adjusted hazard ratio 0.19, 95% CI: 0.08 to 0.48) that was not seen for patients with non-BRCA-like^CGH tumors (adjusted hazard ratio 0.90, 95% CI: 0.53 to 1.54) (P = 0.004). Half of all BRCA-like^CGH tumors were ER-positive.

Conclusions

Distinct aCGH patterns differentiated between HER2-negative patients with a markedly improved outcome after adjuvant treatment with an intensified DNA-DSB-inducing regimen (BRCA-like^CGH patients) and those without benefit (non-BRCA-like^CGH patients).