Spatial and temporal expansion of intrahepatic metastasis by molecularly‐defined clonality in multiple liver cancers

Multiple hepatocellular carcinoma (HCC) is divided into two categories: intrahepatic metastasis (IM), which is a true relapse of HCC, and multicentric origin (MO), which is a second primary tumor. Clinical diagnosis of multiple HCC is usually made based on tumor location and/or time to recurrence; however, it is often difficult to distinguish the two types of multiple HCC. Using 41 matched pairs of multiple HCC specimens, we confirmed the accuracy of clinical diagnoses using exome sequence data and investigated the importance of discriminating the type of multiple HCC. Genomic analysis revealed that 18 (43.9%) patients diagnosed as having genomic IM had common mutations in a pair of HCC tumors with the main tumor of these patients being more progressive compared to those with genomic MO. The accuracy of clinical diagnosis based on lobe (Definition 1) and segment (Definition 2) were 68.3% and 78.0%, respectively. Intriguingly, recurrence ≥2 years after initial surgery for 3 patients was IM. The survival of patients with clinical IM was significantly shorter than for those with clinical MO based on both Definition 1 (P = 0.045) and Definition 2 (P = 0.043). However, mean survival was not different between the patients with genomic IM and those with MO (P = 0.364). Taken together, genomic analysis elucidated that liver cancer may spread more extensively and more slowly than previously thought. In addition, distinguishing multiple HCC as IM or MC may have provided biological information but was not of clinical importance with respect to patient prognosis.     

通脉降脂饮对痰瘀互阻型动脉粥样斑块稳定性的影响

目的:观察通脉降脂饮治疗痰瘀互阻型动脉粥样硬化患者的临床疗效,探讨通脉降脂饮干预动脉粥样硬化斑块稳定性的可能机制。方法:选取2018年1-12月在佛山市禅城区人民医院门诊就诊或健康体检的急性心脑血管事件后2周的患者175例,随机分为对照组86例和观察组89例,对照组口服阿司匹林肠溶片、辛伐他汀分散片治疗,观察组在对照组治疗的基础上加服通脉降脂饮,日1剂,两组疗程均为6个月。观察两组患者临床疗效及相关指标变化情况。结果:对照组有效率为83.72%,观察组有效率为93.26%,两组有效率比较,差异有统计学意义(P<0.05)。两组患者治疗前血清超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)、金属基质蛋白酶9(Matrix metalloproteinase 9,MMP-9)、血同型半胱氨酸(homocysteine,Hcy)比较,差异无统计学意义(P>0.05)。治疗后两组血清Hs-CRP、MMP-9、Hcy与治疗前比较,差异有统计学意义(P<0.05);两组急性心脑血管事件后血清Hs-CRP、MMP-9、Hcy与治疗前比较,差异有统计学意义(P<0.05);急性心脑血管事件后血清Hs-CRP、MMP-9、Hcy组间比较,差异有统计学意义(P<0.05)。对照组急性心脑血管事件发生率为23.26%,治疗组急性心脑血管事件发生率为11.24%,两组急性心脑血管事件发生率比较,差异有统计学意义(P<0.05)。两组均未发生死亡、肝肾异常等病例。结论:通脉降脂饮可以降低动脉粥样硬化患者血清Hs-CRP、MMP-9、Hcy,减少急性心脑血管事件的发生。     

气象因素对钉螺密度变化的影响分析

目的 研究自然条件下气象因素对钉螺密度变化的影响,为控制血吸虫病及其钉螺扩散提供科学依据。方法 收集1990－2014年湖北省潜江市春季查螺资料及地面气象观测数据,采用一阶自回归分析方法对实际钉螺密度进行趋势拟合与分解,利用相关分析法对钉螺密度变化率与不同时段、不同气象要素进行相关性分析。结果 对钉螺密度影响最大的气象因子是温度,其次为降水;其中1月平均最低气温和冬季平均最低气温分别是钉螺密度变化率、活螺框变化率影响最大的温度因子;1月平均最低温度升高(或降低)1 ℃,将会导致钉螺密度上升(或下降) 5.080%～6.710%;冬季平均最低温度升高(或降低)1 ℃,活螺框变化率上升(或下降)15.521%～15.928%。降水对钉螺密度影响最大的时段是上年11月至当年4月,该时段内降水偏少20%以上,有利于降低钉螺密度。9－11月日照与钉螺密度变化率、活螺框变化率存在一定相关性。在相关分析基础上分别建立了钉螺密度变化率、活螺框变化率与气象因子的统计回归模型。结论 在12月到来之前清除有螺区杂草有利于降低地表温度和土壤水分含量,能取得一定的灭螺效果。伴随全球气候变化湖北省冬季温度升高趋势明显,可能引发钉螺密度升高。     

血清β-Amyloid水平在膝骨关节炎发生评估中的应用价值

目的：探讨膝骨关节炎（KOA）患者血清中β-Amyloid水平与KOA发生及预后的相关性。方法：从温州医科大学附属第二医院育英儿童医院住院患者中选取56例经全膝关节置换或膝关节镜手术治疗的KOA患者为试验组和25 例非KOA患者为对照组。试验组根据X线Kellgren-Lawrence（K-L）分级方法分级，同时收集手术患者术前术后血清标本，采用双抗体夹心酶联免疫吸附法（ELISA)测定血清β-Amyloid水平后，绘制受试者工作特征（ROC）曲线评价血清β-Amyloid对KOA的预测价值，采用Spearman秩相关分析患者血清β-Amyloid水平与KOA的相关性，应用Pearson相关性分析患者手术前后血清β-Amyloid变化值与患者住院时间的相关性。结果：试验组患者血清β-Amyloid水平高于对照组（P ＜0.001）；Logistic回归分析显示β-Amyloid是KOA患病的危险因素（OR =15.122，P ＜0.05)；ROC曲线分析显示，β-Amyloid cut off值等 于0.770，曲线下面积（AUC）为0.752，95%CI =0.636～0.867，敏感度85.5%，特异度60.0%；K-L2组患者血清β-Amyloid低于K-L3/4组患者（P =0.041）；β-Amyloid的表达与KOA严重程度分级呈显著正相关（r =0.332，P =0.013）；术前KOA患者血清β-Amyloid水平高于术后（P =0.002），KOA患者手术前后血清β-Amyloid变化 值与患者住院时间呈显著负相关（r =-0.949，P ＜ 0.001）。结论：β-Amyloid是KOA患病的危险因素，血清β-Amyloid水平可能成为一种潜在的评估KOA发生及预后的生物标志物。     

Characteristics and survival for HIV-associated multicentric Castleman disease in Malawi

Introduction

Clinical reports of multicentric Castleman disease (MCD) from sub-Saharan Africa (SSA) are scarce despite high prevalence of HIV and Kaposi sarcoma-associated herpesvirus (KSHV). Our objective is to describe characteristics and survival for HIV-associated MCD patients in Malawi. To our knowledge, this is the first HIV-associated MCD case series from the region.

Methods

We describe HIV-positive patients with MCD in Lilongwe, and compare them to HIV-associated lymph node Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) patients treated at our centre. All patients were enrolled into a prospective longitudinal cohort study at a national teaching hospital and cancer referral centre serving half of Malawi''s 16 million people. We included adult patients≥18 years of age with HIV-associated MCD (n=6), lymph node KS (n=5) or NHL (n=31) enrolled between 1 June 2013 and 31 January 2015.

Results and discussion

MCD patients had a median age of 42.4 years (range 37.2–51.8). All had diffuse lymphadenopathy and five had hepatosplenomegaly. Concurrent KS was present for one MCD patient, and four had performance status ≥3. MCD patients had lower median haemoglobin (6.4 g/dL, range 3.6–9.3) than KS (11.0 g/dL, range 9.1–12.0, p=0.011) or NHL (11.2 g/dL, range 4.5–15.1, p=0.0007). Median serum albumin was also lower for MCD (2.1 g/dL, range 1.7–3.2) than KS (3.7 g/dL, range 3.2–3.9, p=0.013) or NHL (3.4 g/dL, range 1.8–4.8, p=0.003). All six MCD patients were on antiretroviral therapy (ART) with median CD4 count 208 cells/µL (range 108–1146), and all with HIV RNA <400 copies/mL. Most KS and NHL patients were also on ART, although ART duration was longer for MCD (56.4 months, range 18.2–105.3) than KS (14.2 months, range 6.8–21.9, p=0.039) or NHL (13.8 months, range 0.2–98.8, p=0.017). Survival was poorer for MCD patients than lymph node KS or NHL.

Conclusions

HIV-associated MCD occurs in Malawi, is diagnosed late and is associated with high mortality. Improvements in awareness, diagnostic facilities, treatment and supportive care are needed to address this likely under-recognized public health problem in SSA.     

A Novel Segment Classification for Multifocal and Multicentric Breast Cancer to Facilitate Breast‐Conservation Treatment

Breast conservation treatment (BCT) is an appropriate alternative to mastectomy for the treatment of unifocal breast cancer. Multifocal and multicentric breast cancers (MFMCBC) challenge conventional indications for BCT and are often treated with mastectomy. Following progress in treatment strategies for unifocal tumors, there was a movement to evaluate the use of BCT for MFMCBC. Now a growing body of evidence from retrospective data has emerged, demonstrating acceptable local control and overall survival rates with BCT for MFMCBC. Prospective studies are needed to confirm these findings. One of the possible barriers to such trials is the absence of a standardized classification and nomenclature for MFMCBC at this point in time. A novel segment classification is presented in this article in an endeavor to overcome this deficiency and allow future work on this issue.     

Uncovering the genomic heterogeneity of multifocal breast cancer

Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between MFBC lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal MFBC involved the identification of non‐silent coding mutations in 360 protein‐coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade, ER, and HER2 status. Mutations were classified as ‘oncogenic’ in the case of recurrent substitutions reported in COSMIC or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole‐genome rearrangement screen was further conducted in 8/36 patients. Twenty‐four patients (67%) had substitutions/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three‐quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution/indels, with inter‐lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome‐wide analyses of a limited number of patients identified a common somatic background in all studied MFBCs, including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter‐lesion heterogeneity in one‐third, despite similar pathological features. This implies that deeper molecular characterization of all MFBC lesions is warranted for the adequate management of those cancers. © 2015 The Authors. Pathological Society of Great Britain and Ireland.     

2485例常规结肠镜筛查结肠息肉检出情况分析

目的了解不同性别和年龄者结肠息肉发病情况。方法按性别、年龄、发病部位以及病理学结果等因素对该院接受常规结肠镜检查的2 485例患者结肠息肉及结肠癌发病情况进行分析。结果 2 485例患者中结肠息肉检出率为35.6%,结肠癌检出率为5.8%,其中男性结肠息肉检出率为40.9%,结肠癌检出率为7.7%;女性结肠息肉检出率为30.5%,结肠癌检出率为3.9%。检出率随着年龄而增加,结肠息肉及结肠癌检出高峰均在70岁年龄组,50岁以上年龄组男性结肠息肉及结肠癌检出率均明显高于女性(P0.01)。息肉以炎性息肉为主,腺瘤性息肉次之,以左半结肠为主。结论结肠息肉是年龄相关性疾病,其存在年龄及性别差异,男性结肠息肉及结肠癌检出率高于女性,男女性结肠息肉及结肠癌检出率均随年龄增长而增加,男女40岁以上息肉检出率明显升高,对40岁以上有肠道症状者应进行结肠镜筛查。     

腹腔镜与开腹手术在脾切除术中的应用效果与术后感染发生的危险因素

目的：探讨腹腔镜与开腹手术在脾切除术中的应用效果与术后感染发生的危险因素。方法：172例需行脾切除手术治疗患者根据随机抽签原则分为治疗组与对照组,对照组予常规开腹脾切除术,治疗组予腹腔镜下脾切除术,观察两组患者的预后效果,进行术后感染的危险因素分析。结果：治疗组术中出血量、术后胃肠功能恢复时间和术后住院时间明显少于对照组。治疗组术后感染发生率为1.2%明显低于对照组的5.8%。多因素非条件Logistic 回归分析显示影响脾切除术后感染发生的独立危险因素主要为开腹手术、年龄和并发糖尿病。结论：脾切除术后感染与开腹手术、年龄和并发糖尿病有关,腹腔镜下脾切除能促进患者的康复,减少术后并发症的发生,值得推广应用。     

Total ankle replacement in patients under the age of 50. Should the indications be revised?

BackgroundHigh physical demand and young age are currently considered contraindications for total ankle replacement. This study aimed to compare its results between patients under the age of 50 and those aged 50 or older.Methods103 patients derived from an ongoing prospective multicentric study with a mean follow-up of 41 (range, 24–72) months were included in this study. Clinical status (AOFAS score), range of motion (ROM), complication and survivorship rates were compared between <50 and ≥50 patients.ResultsROM and AOFAS score were significantly higher, as were their increases relatively to pre-operative values in patients <50. Complication and survivorship rates were comparable between both groups.ConclusionsAt medium-term, ankle replacement is at least as effective in patients under the age of 50 as in those with aged 50 or older. Long-term results will allow to assess whether surgical indications for should be revised.