新生滋养血管在动脉粥样硬化形成中的作用及临床意义

动脉粥样硬化(As)病变的主要临床危险性在于斑块的不稳定性、易损性。斑块内新生滋养血管(VV)具有结构缺陷,其脆性大、渗漏性高,容易破裂出血,促进炎症反应,也为血细胞及血液可溶性成分进入斑块提供通道,促进As斑块的形成,并且与斑块内出血、斑块破裂及临床心脑血管事件的发生密切相关。深入研究新生滋养血管的功能及关键信号途径在As中的作用,有望从根本上阻止稳定斑块发展为易损斑块,或者阻止不稳定斑块破裂及其并发症的发生。     

Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab

AIM:To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease.METHODS:We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts:(1) the AGITG MAX trial(Phase Ⅲ randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine,bevacizumab and mitomycin C);(2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer(TRACC) registry(any first-line regimen ± bevacizumab);and(3) two cancer centres in New South Wales,Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre(NSWCC) from January 2005 to Decenber 2012,(any first-line regimen ± bevacizumab).For the AGITG MAX trial capecitabine was compared to the other two arms(capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycin C).In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases.Secondary endpoints included progression-free survival,chemotherapy duration,and overall survival.Time-toevent outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.RESULTS:Eighty-four MAX,179 TRACC and 69 NSWCC patients had peritoneal disease.There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts.Of the patients without peritoneal disease in the MAX trial,4/300(1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123(0.8%) in the capecitabine alone arm.In the TRACC registry 3/126(2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53(1.9%) in the chemotherapy alone arm.In a further analysis of patients without peritoneal metastases in the TRACC registry,the rate of gastrointestinal perforations was 9/369(2.4%) in the chemotherapy/bevacizumab group and 5/177(2.8%) in the chemotherapy alone group.The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts:MAX 6.9 m vs 4.9 m,HR = 0.64(95%CI:0.42-1.02);P = 0.063;TRACC 9.1 m vs 5.5 m,HR = 0.61(95%CI:0.37-0.86);P = 0.009;NSWCC 8.7 m vs 6.8 m,HR = 0.75(95%CI:0.43-1.32);P = 0.32.Chemotherapy duration was similar across the groups.CONCLUSION:Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.     

Coronary artery wall enhances with intracoronary injection of echocontrast media during in vivo intravascular ultrasound.

Currently, vascularity of the coronary artery wall can be assessed only in vitro. We sought to determine if there is any contrast enhancement of the coronary artery wall after injection of echocontrast media during in vivo intravascular ultrasound imaging, which may represent blood flow within the wall supplied by the vasa vasorum.     

A phase II study of first-line biweekly capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer

Purpose

This phase II study was conducted to determine the efficacy and safety of capecitabine and bevacizumab in untreated elderly metastatic colorectal cancer patients.

Methods

Patients received 1500 mg/m²/dose of capecitabine twice daily × 7 days and bevacizumab at 5 mg/kg on day 1, in 2 week-cycles.

Results

The study was closed early, due to poor accrual, after a total of 16 patients enrolled. Four patients had an objective response and 11 patients had stable disease. The median time to progression and overall survival were 9.5 and 21.2 months, respectively. The most common grade ≥ 3 toxicities included diarrhea (13%) and hand and foot syndrome (25%). Three patients had an arterial thrombotic event and one patient developed a bowel perforation.

Conclusions

In this underpowered phase II study in elderly patients with metastatic colorectal cancer, capecitabine plus bevacizumab was associated with considerable clinical activity but at an increased risk of hand and foot syndrome and arterial thrombotic events.     

A meta-analysis of randomized controlled trials comparing chemotherapy plus bevacizumab with chemotherapy alone in metastatic colorectal cancer

Purpose  Bevacizumab has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients when combined with chemotherapy. Several randomized clinical studies have evaluated bevacizumab in combination with chemotherapy. Meta-analysis was performed to better assess the efficacy and safety of bevacizumab with chemotherapy for mCRC. Materials and methods  Five clinical trials randomizing a total of 3,103 mCRC patients to chemotherapy alone or to the combined treatment of chemotherapy plus bevacizumab were identified. The efficacy data included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR), and the safety data contained the 60-day all-cause mortality rate, adverse events (AEs), and specific toxicity such as hypertension, thrombosis, bleeding, proteinuria, gastrointestinal perforation, diarrhea, and leucopenia. Result  There was a significant PFS benefit (P = 0.00; hazards ratio [HR] = 0.66) and OS benefit (P = 0.00; HR = 0.77) in favor of the combined treatment. The ORR was significantly higher on the bevacizumab-containing arm (P = 0.021; relative risk [RR] = 1.5), while CR was comparable between the two arms (P = 0.09). A higher incidence of grade 3/4 AEs, grade 3/4 hypertension, grade 3/4 thromboembolic/thrombotic events, grade 3/4 bleeding, and gastrointestinal perforation was associated with the bevacizumab group. The two treatment groups were similar in terms of grade 3/4 proteinuria, grade 3/4 leukopenia, grade 3/4 diarrhea, and the 60-day all-cause mortality rate. Conclusion  The addition of bevacizumab to chemotherapy confers a clinically meaningful and statistically significant improvement in OS, PFS, and ORR. Its side effects are predictable and manageable and do not compound the incidence or severity of toxicities from chemotherapy.     

长春瑞滨联合贝伐单抗治疗非小细胞肺癌的临床分析

目的分析长春瑞滨联合贝伐单抗治疗非小细胞肺癌(NSCLC)的临床疗效及生存情况。 方法选择我院2017年4月至2020年3月接诊的42例NSCLC患者作为观察对象,依据临床治疗方案将患者分为观察组22例和对照组20例,给予对照组患者顺铂+长春瑞滨治疗,观察组患者在对照组基础上联合贝伐单抗治疗。评估两组患者治疗2周后的临床疗效、血清肿瘤因子[血清血管生成素样蛋白2(ANGPTL2)、抗菌肽人类阳离子抗菌蛋白18(hCAP18)及血清癌胚抗原(CEA)]水平、药物不良反应及12个月随访后的生存情况。 结果观察组疾病控制率(81.82%)高于对照组(60.00%),差异有统计学意义(P<0.05);治疗后,两组患者的血清hCAP18、CEA及ANGPTL2水平均低于治疗前,且观察组较对照组更低,差异有统计学意义(P<0.05);观察组1年生存率(77.27%)高于对照组(45.00%),差异具有统计学意义(P<0.05);两组患者的不良反应发生率比较差异无统计学意义(P>0.05)。 结论给予NSCLC患者长春瑞滨联合贝伐单抗治疗,有助于改善患者的临床疗效,提高患者的疾病控制率,降低患者的血清hCAP18、CEA及ANGPTL2水平,提高患者的1年生存率,且安全性较好。     

Preoperative administration of bevacizumab is safe for patients with colorectal liver metastases

AIM:To assess the impact of preoperative neoadjuvant bevacizumab(Bev)on the outcome of patients undergoing resection for colorectal liver metastases(CLM). METHODS:Eligible trials were identified from Medline, Embase,Ovid,and the Cochrane database.The data were analyzed with fixed-effects or random-effects models using Review Manager version 5.0. RESULTS:Thirteen nonrandomized studies with a total of 1431 participants were suitable for meta-analysis. There was no difference in overall morbidity and severe complications between the Bev+group and Bev-group (43.3%vs 36.8%,P=0.06;17.1%vs 11.4%,P=0.07,respectively).Bev-related complications including wound and thromboembolic/bleeding events were also similar in the Bev+and Bev-groups(14.4%vs 8.1%, P=0.21;4.1%vs 3.8%,P=0.98,respectively).The incidence and severity of sinusoidal dilation were lower in patients treated with Bev than in patients treated without Bev(43.3%vs 63.7%,P<0.001;16.8%vs 46.5%,P<0.00,respectively). CONCLUSION:Bev can be safely administered before hepatic resection in patients with CLM,and has a protective effect against hepatic injury in patients treated with oxaliplatin chemotherapy.     

Sustained treatment response of metastatic hepatocellular carcinoma with bevacizumab and sorafenib

The overall survival for patients with advanced hepatocellular carcinoma(HCC)is still limited.Although the multi-kinase inhibitor sorafenib has recently been approved for this disease,response rates are still low and patients often face dose-limiting toxicities which lead to a reduction in prognosis and treatment success.We here report a patient with metastasized HCC who shows a sustained response for more than 30 mo to sorafenib therapy after failure of a first line therapy with gemcitabine,oxaliplatin and...     

从滋养血管成熟化探讨稳定动脉粥样硬化易损斑块的作用

动脉粥样硬化(As)疾病在各种易损因素的影响下,最终导致斑块的形成、破裂。在这一过程中斑块内新生血管的数量、通透性成为关键因素,因此,对于新生血管的调节成为近几年As疾病的治疗策略。然而,仅仅通过抑制新生血管的进展具有一定局限性,怎样促进斑块内滋养血管成熟化将成为稳定As易损斑块新的治疗途径。本文综述了滋养血管成熟化相关生长因子及信号通路,以期为As易损斑块新的治疗奠定理论基础。     

Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

AIM： To investigate the efficacy and safety of cape- citabine plus irinotecan ＋ bevacizumab in advanced or metastatic colorectal cancer patients. METHODS： Forty six patients with previously untreated, locally-advanced or metastatic colorectal cancer （mCRC） were recruited between 2001-2006 in a pro- spective open-label phase Ⅱ trial, in German commu- nity-based outpatient clinics. Patients received a stan- dard capecitabine plus irinotecan （CAPIRI） or CAPIRI plus bevacizumab （CAPIRI-BEV） regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of 〉 grade 2 toxicity. The treatment choice of bevacizumab was at the discretion of the physician. The primary endpoints were response and toxicity and sec- ondary endpoints included progression-free survival and overall survival. RESULTS： In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients （47% vs 24%）, and more patients had colon as the primary tumor site （58.8% vs 48.2%） with fewer patients having sigmoid colon as primary tumor site （5.9% vs 20.7%）. Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev： 82% vs 58.6%. Partial response rates were 29.4% and 34.5%, and tumor control rates were 70.6% and 75.9%, respectively. No complete re- sponses were observed. The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CA- PIRI-Bev, respectively. The median overall survival for CAPIRI was 15 mo （458 d） and for CAPIRI-Bev 24 mo （733 d）. These differences were not statistically different. In the CAPIRI-Bev, group, two patients under- went a full secondary tumor resection after treatment, whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION： Both regimens were well tolerated and offered effective tumor growth control in this out- patient setting. Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.     

Systemic lupus erythematosus and the risk of perioperative major adverse cardiovascular events

Systemic lupus erythematosus (SLE) is a significant risk factor for cardiovascular disease. The relationship between SLE and perioperative cardiovascular risks following non-cardiac surgery is uncertain. We investigated associations between a diagnosis of SLE and outcomes following major non-cardiac surgery in a large national database from the United States. Patients age?≥?18 years requiring major non-cardiac surgery were identified from Healthcare Cost and Utilization Project’s National Inpatient Sample data from 2004 to 2014. Systemic lupus erythematosus and perioperative major adverse cardiovascular events (MACE; myocardial infarction, ischemic stroke or death) were defined by ICD-9 diagnosis codes. Perioperative MACE were reported for SLE patients stratified by age and sex. From 2004 to 2014, a total of 17,853,194 hospitalizations for major non-cardiac surgery met study inclusion criteria. SLE was identified in 70,578 (0.4%) hospitalizations. Overall, the frequency of perioperative MACE was higher in patients with vs. without SLE [2.4 vs. 2.0%, p <?0.001; adjusted OR (aOR) 1.25; 95% CI 1.18–1.31]. Perioperative MACE associated with SLE was largely driven by increased death (aOR 1.58 95% CI 1.40–1.77) and myocardial infarction (aOR 1.32; 95% CI 1.05–1.66) in younger patients with SLE. The increased risk of perioperative MACE associated with SLE in younger patients was attenuated with increasing age. A diagnosis of SLE is associated with increased risk of perioperative MACE, particularly among younger patients. Efforts to improve the perioperative management and outcomes of patients with SLE are needed.     

XELOX联合贝伐珠单克隆抗体方案转化治疗同时性结肠癌并发肝转移患者初步研究

目的 探讨应用奥沙利铂和卡培他滨(XELOX)联合贝伐珠单克隆抗体方案转化治疗同时性结肠癌并发肝转移患者疗效及安全性。方法 2015年6月～2017年7月我院诊治的41例初始不可切除的结肠癌并发肝转移患者,实施了XELOX联合贝伐珠单克隆抗体方案的转化治疗,观察了转化治疗应答率、转化结果、不良反应和总生存期(OS)。结果 41例初始不可切除的结肠癌并发肝转移患者均接受了不少于4个疗程的转化治疗。在转化治疗后,31例(75.6%)患者呈部分缓解(PR),其中14例(34.1%)患者接受了根治性手术;在转化治疗后随访13～26个月(中位随访时间为18个月),转化手术组与未手术组1 a总生存率分别为92.3%(失访1例)和66.7%,经Log-rank 检验发现转化手术组患者总生存期显著长于未手术组(P=0.019)。结论 应用贝伐珠单克隆抗体联合XELOX方案治疗同时性结肠癌并发肝转移患者安全有效,部分初始不可切除患者可以通过转化治疗再次获得手术机会,而一旦实施转化手术,有望延长患者的生存时间。     

Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk

OBJECTIVES: This prospective population study was conducted to assess the role of elevated lipoprotein(a) [Lp(a)] as a coronary risk factor. BACKGROUND: The role of elevated Lp(a) as a risk factor for coronary heart disease is controversial. In addition, little attention has been paid to the interaction of Lp(a) with other risk factors. METHODS: A total of 788 male participants of the Prospective Cardiovascular Münster (PROCAM) study aged 35 to 65 years were followed for 10 years. Both Lp(a) and traditional cardiovascular risk factors (e.g., age, low density lipoprotein [LDL] cholesterol, high density lipoprotein [HDL] cholesterol, triglycerides, systolic blood pressure, cigarette smoking, diabetes mellitus, angina pectoris, and family history of myocardial infarction) were evaluated in 44 men who suffered from myocardial infarction, and in 744 men who survived without major coronary events or stroke. A multiple logistic function algorithm was used to estimate global cardiovascular risk by the combined effects of traditional risk factors. RESULTS: Overall, the risk of a coronary event in men with an Lp(a) > or =0.2 g/liter was 2.7 times that of men with lower levels (95% confidence interval [CI]: 1.4 to 5.2). This increase in risk was most prominent in men with LDL cholesterol level > or =4.1 mmol/liter (relative risk [RR]: 2.6; 95% CI: 1.2 to 5.7), with HDL cholesterol < or =0.9 mmol/liter (RR 8.3; 95% CI: 2.0 to 35.5), with hypertension (RR 3.2; 95% CI: 1.4 to 7.2), or within the two highest global risk quintiles (relative risk: 2.7; 95% CI: 1.3 to 5.7). CONCLUSIONS: Lp(a) increases the coronary risk, especially in men with high LDL cholesterol, low HDL cholesterol, hypertension and/or high global cardiovascular risk.     

The risk of subsequent cancer and arterial cardiovascular events in patients with superficial vein thrombosis in the legs

Although it has been clearly demonstrated that venous thromboembolism is associated with an increased risk of subsequent overt cancer and arterial cardiovascular events in comparison with control populations, whether this association also applies to patients with isolated (ie, without concomitant involvement of the deep vein system) superficial vein thrombosis (SVT) in the legs is unknown. In 737 consecutive patients with isolated SVT not involving the sapheno-femoral junction, we conducted a retrospective investigation to assess the rate of cancer and that of arterial cardiovascular events occurring during follow-up. The event rates were compared with those occurring in 1438 controls having comparable characteristics. Both cases and controls were followed-up for an average period of 26 ± 8 months (range, 3-45). Malignancy was diagnosed in 26 cases (3.5%) and 56 controls (3.9%), leading to a hazard ratio of 0.86 (95% confidence interval, 0.55%-1.35%). Arterial cardiovascular events occurred in 32 cases (4.3%) and 63 controls (4.4%), leading to a hazard ratio of 0.97 (95% confidence interval, 0.63%-1.50%). We conclude that the occurrence of isolated SVT in the legs does not place patients at an increased risk of malignancies or arterial cardiovascular events. Whether this conclusion also applies to patients whose thrombosis involves the sapheno-femoral junction remains to be demonstrated.     

Quality of life in older patients with systolic and diastolic heart failure

AIMS: To get insight into the quality of life of a clinical practice sample of patients with heart failure that are admitted to the hospital. Secondly to determine differences between patients with systolic and diastolic dysfunction and finally to describe factors relating to quality of life. METHODS: Three dimensions of quality of life (functional capabilities, symptoms and psychosocial adjustment to illness) were assessed during interviews of 186 patients with chronic heart failure. In addition, data on demographic, clinical and self-care characteristics were collected and patients completed a 6-min walk. RESULTS: On average patients walked 172 m in 6 min and reported functioning in daily life at a mean level of 4.5 MET. Patients experienced four different symptoms of heart failure. Most of them described dyspnea, fatigue, sleep disturbance and ankle oedema. Problems with psychosocial adaptation occurred mostly in social and vocational domains. Overall well-being of patients was rated as 6.4 on a 10-point scale. In regard to quality of life, the only differences between patients with systolic and diastolic heart failure was the occurrence of ankle oedema and health-care orientation. The variance in components of quality of life were partly explained by demographics and clinical characteristics. All three dimensions of quality of life were related to ability for self-care. CONCLUSION: Patients with heart failure seen in clinical practice are often not comparable to patients described in major clinical trials or patients that are admitted for transplant evaluation. Their functional capabilities are more compromised, but they may have fewer problems with psychosocial adjustment. Patients with normal systolic dysfunction also report a low quality of life. It could be important to enhance self-care abilities of patients to improve psychosocial adaptation to illness.