Managing patients with metastatic colorectal cancer on bevacizumab

Bevacizumab (Avastin) is a humanized monoclonal antibody that inhibits the activity of vascular endothelial growth factor (VEGF), a key molecule controlling tumour blood vessel formation (angiogenesis). By inhibiting VEGF and thus tumour angiogenesis, bevacizumab inhibits tumour growth and survival. In patients with metastatic colorectal cancer (CRC), first-line use of bevacizumab in combination with fluoropyrimidine-based chemotherapy improves outcomes compared with chemotherapy alone. The side-effect profile of bevacizumab does not overlap with that of conventional chemotherapy, and it does not significantly exacerbate chemotherapy-induced adverse events. Specific side-effects of special interest for bevacizumab include hypertension, proteinuria, arterial thromboembolic events, wound-healing complications, bleeding events and gastrointestinal perforation. Oncology nurses are key to early recognition and management of side-effects, in addition to having a key role in patient education, facilitating the optimal use of bevacizumab and thus survival of patients with metastatic CRC.     

循环肿瘤细胞的检测在结直肠癌中的应用

结直肠癌是最常见的癌症之一,尽管手术、化疗、放疗的联合应用使转移患者的生存率有所提高,但结果仍不令人满意。检测循环肿瘤细胞是当前研究的热点之一,被越来越多的应用于各种实体瘤。科技的日新月异使循环肿瘤细胞的检测变得更加可行,精确计数以及分子生物学分析对于肿瘤患者的预后判断、疗效评价以及个体化治疗均有重要的指导意义。本文将探讨循环肿瘤细胞的检测技术及在结直肠癌方面的临床研究进展。     

大肠癌c-met基因mRNA定量表达研究

目的：检测c-met基因在大肠癌中的表达情况及其在大肠癌侵袭转移过程中的变化规律。方法：采用荧光实时定量PCR方法检测30例大肠癌及切端正常大肠组织c-met基因的mRNA转录水平，采用免疫组织化学sP法检测其蛋白表达情况。结果：c-met在63％（19／30）的正常大肠组织和90％（27／30）的大肠癌组织中阳性表达。大肠癌组织中c-met在mRNA转录和蛋白水平的表达均高于正常大肠组织（P〈0．05）。c-met的表达与大肠癌的淋巴结转移、浸润深度和Dukes分期明显相关，差异具有显著性（P〈0.05）；而与大肠癌的病理组织学类型和分化程度无关（P〉0．05）。结论：c-met在大肠癌的侵袭与转移中发挥着重要作用。检测c-metmRNA含量可作为判断大肠癌浸润、转移的良好参考指标。并可为将来大肠癌的诊断、分期和治疗开辟一个新的方向     

卡培他滨维持治疗转移性结肠、直肠癌的疗效及安全性观察

目的评价卡培他滨维持治疗以延长转移性结肠、直肠癌一线化疗后的无疾病进展时间（TTP）的疗效及安全性。方法 50例转移性结肠、直肠癌患者一线化疗后达到稳定,按患者意愿分成2组,治疗组（n=30）给予单药卡培他滨口服,2次/d,餐后服用,2 500 mg/（m2.d）,连续服用14 d后停药7 d,治疗周期为21 d,至少治疗2个周期,直至病情进展或毒性不能耐受;对照组（n=20）采用持续化疗,定期监测,直至病情进展。结果治疗组中位TTP（mTTP）为9.2个月,中位疾病控制时间（mDDC）13.7个月;对照组mTTP为6.1个月,mDDC为9个月,2组mTTP、mDDC差异均有统计学意义。治疗组不良反应多数为Ⅰ~Ⅱ级。结论转移性结肠、直肠癌患者在一线化疗达到稳定后给予单药卡培他滨维持化疗,可显著延长患者TTP,且耐受性良好。     

mRNA microarray profiling identifies a novel circulating HTRA2 for detection of gastric cancer

BackgroundmRNAs have been shown to be critical biomarkers or therapeutic targets for human diseases. However, only a few of them have been studied as blood‐based biomarkers for gastric carcinoma (GC) detection.MethodsmRNA expression profiles for GC were screened using plasma samples from 10 GC patients with different TNM stages and 5 healthy individuals as controls. One candidate tumor‐related mRNA named HTRA2 was then evaluated in GC samples with quantitative real‐time polymerase chain reaction (qRT‐PCR). TCGAportal, UALCAN, and TISCH database were used to explore the function of HTRA2 in GC. Finally, the effect generated by HTRA2 expression on cell proliferating, invading, and migrating processes was assessed in vitro with knockdown and over‐expression strategies.ResultsHTRA2 displayed noticeable increase inside GC plasma compared with control cases. Higher expression of HTRA2 displayed a correlation to higher clinicopathological stage and worse prognosis. HTRA2 knocking down down‐regulated GC cells'' proliferating, invading, and migrating states, while HTRA2 over‐expression exerted the inconsistent influence. HTRA2 protein, which may interact with PINK1, PARL, and CYCS, was mainly located in the mitochondria of cells and primarily involved cellular response and metabolic signaling pathway. Immune factors may interact with HTRA2 in GC, and HTRA2 was found noticeably linked with immunosuppressor such as CD274, IDO1, and TIGIT.ConclusionOne plasma HTRA2 can be an emerging diagnosis‐related biomarker to achieve GC detecting process, but the particular regulatory effect still needs to be further explored.     

The effect of foot reflexology on pain in patients with metastatic cancer

Thirty-six oncology inpatients participated in this third pilot study investigating the effects of foot reflexology in which equianalgesic dosing was calculated. Foot reflexology was found to have a positive immediate effect for patients with metastatic cancer who report pain, although there was no statistically significant effect at 3 hours after intervention or at 24 hours after intervention. Further study is suggested for foot reflexology delivered by family in the homes for management of cancer pain.     

结直肠癌患者外周血CEA-mRNA表达的研究

目的 检测结直肠癌患者外周血中的循环肿瘤细胞癌胚抗原（CEA）mRNA的表达,并分析其临床价值。方法 40例有明确临床肿瘤病灶存在的结肠癌患者,20例结肠息肉患者和40例健康志愿者,分别以逆转录PCR（RT-PCR）检测其外周血中CEA mRNA的表达。结果 40例结肠癌患者外周血中CEA mRNA表达的阳性率为45.0%（18/40）,而健康对照组均为阴性,两者比较有显著性差异（P〈0.001）;20例结肠息肉患者中CEA mRNA表达阳性率为10%（2/20）;CEA mRNA阳性表达率与肿瘤分期相关,而与肿瘤细胞分化程度并不相关。结论 结直肠癌患者外周血中CEA mRNA的表达的检测对肿瘤的分期、决定治疗手段、判断疗效和预后有着重要的临床价值。     

CK20 mRNA和hTERT mRNA在大肠癌围手术期血行微转移中的转录特征

目的 探讨细胞角蛋白20(CK20)mRNA和人端粒酶催化亚单位(hTERT)mRNA作为大肠癌围手术期血行微转移标志物的价值.方法 采用逆转录聚合酶链反应(RT-PCR)检测40例大肠癌患者术前、术中及术后外周血CK20 mRNA和hTERTmRNA的表达,并对不同分化程度、不同Dukes分期的大肠癌患者CK20 mRNA和hTERT mRNA的表达进行比较.结果 40例大肠癌患者外周血CK20 mRNA和hTERT mRNA的表达率,术前分别为47.5%(19/40)和45.0%(18/40),术中为70.0%(28/40)和70.0%(28/40),术后为10.0%(4/40)和32.5%(13/40).除术后hTERT mRNA阳性率与术前无显著差异(P＞0.05)外,术中外周血CK20 mRNA、hTERT mRNA阳性率和表达强度(与内参照β-actin比值)均显著高于术前(P＜0.01,P＜0.05),术后明显低于术前和术中(P＜0.01).hTERT mRNA在低分化肿瘤的表达明显高于高、中分化组(P＜0.05),而CK20mRNA在低分化肿瘤的表达强度低于高、中分化组(P＜0.01).大肠癌围手术期Dukes B期和C D期之间CK20 mRNA和hTERT mRNA均无显著性差异(P＞0.05).结论 大肠癌患者围手术期血行微转移的发生几率较高,病理分化程度低者更易发生,但与Dukes分期无明显相关,CK20 mRNA和hTERT mRNA联合检测对大肠癌血液微转移具有较高的敏感性和特异性,是判断围手术期血行微转移的良好标志物.     

The use of biochips opens up new dimensions in diagnostic practice

The past decades have reflected a continuous increase in healthcare costs that is dramatic compared to growth rates of the national economy. Not only this, the legislative demands made on medical services and medical devices have become far more complex. All this makes a strong impact on the field of laboratory diagnostics. Although scientific and technical possibilities have greatly improved, they have done little to reduce costs.     

Basal proteinuria as a prognostic factor in patients with metastatic colorectal cancer treated with bevacizumab

Background

The beneficial effects of bevacizumab, a widely used agent in metastatic colorectal cancer (mCRC), on clinical survival have been proven. This study investigated the correlation of the clinical benefits and prognosis with proteinuria and other parameters.

Methods

The study included mCRC patients receiving bevacizumab. Hypertension, 24-hour urine proteinuria, and other routine parameters were recorded at baseline and at certain intervals during treatment.

Results

The study included 36 consecutive patients. The median progression-free survival (PFS) duration was 10.9 ± 2.6 months, and the median overall survival (OS) was 23 ± 3.1 months. The median PFS was 7.2 months among patients with basal proteinuria above 114 mg/day, whereas the median PFS was 12 months among patients with an equal or lower level (P = 0.010). Similarly, PFS was shorter in patients with high lactate dehydrogenase (LDH) or carcinoembryonic antigen (CEA) levels (LDH, P = 0.022; CEA, P = 0.014). Bevacizumab response's performance status was good (P = 0.05) and was even better in patients with a single liver metastasis (P = 0.034) or hypertension (P = 0.034).

Conclusions

We demonstrated that high basal proteinuria, LDH, or CEA levels may be negative prognostic factors in mCRC patients receiving bevacizumab.     

结肠癌组织中蛋白酶活化受体-1的表达及意义

目的 探讨结肠癌组织中蛋白酶活化受体-1（PAR-1）mRNA的表达情况及其临床意义.方法 实时荧光定量PCR（RT-PCR）检测33例结肠癌患者癌组织及其相应癌旁组织中PAR-1 mRNA的表达情况,分析PAR-1 mRNA与结肠癌分化程度、病理分期以及转移等指标的相关性.结果 结肠癌组织中PAR-1 mRNA的表达明显增高,比邻近癌旁组织平均高4.99倍;二者ΔCt比较,t=9.15,P〈0.01.同时低分化的结肠癌患者组PAR-1 mRNA表达量明显高于中、高分化患者组,P〈0.01;有转移患者组的PAR-1 mRNA表达量明显高于无转移患者组,P〈0.01;而在结肠癌临床Ⅰ~Ⅱ期与Ⅲ~Ⅳ期患者组之间,PAR-1 mRNA表达量差异无统计学意义,P〉0.05.结论 PAR-1 mRNA在结肠癌中高表达,且与结肠癌的分化及是否转移有关.     

Impact of treatment modality on clinical outcome in metastatic colorectal cancer patients stratified by metastatic sites

Objectives: To investigate the impact of location of metastases, and therapeutic modality on clinical outcomes in patients with metastatic colorectal cancer (CRC).

Methods: Data for metastatic CRC patients were sourced from the Surveillance, Epidemiology, and End Results (SEER) database (SEER ID: 15309-Nov2017). Patients were classified as follows: Group 1 patients had only liver metastasis; Group 2 patients had liver and lung metastasis; Group 3 patients had more than two metastasis sites. Patients were treated with surgery alone, radiation alone, or surgery plus radiation. The main study outcomes were (1) cancer-specific mortality and (2) survival benefit associated with treatment modality.

Results: A total number of 15,510 patients were included in this study. In Groups 1 and 2, patients treated with surgery plus radiation had a higher cumulative survival compared to other treatment groups (p-value <.001). Group 3 patients showed no significant difference in cumulative survival between the different treatment modalities (p-value = .218). Group 1 patients who received surgery plus radiation had a significantly lower risk of mortality compared to the other treatment groups (p-value <.001), and Group 2 patients who either received radiation treatment alone or surgery plus radiation had a significantly lower risk for mortality than patients who received other treatment modalities (p-value <.001). Multivariate analysis adjusting for known prognostic factors such as tumor sidedness and race did not alter the observed risk conferred by metastasis sites and treatment modalities.

Conclusion: Stratification by metastases sites, and by treatment modality can help multidisciplinary teams to reach a treatment consensus for metastatic CRC.     

西妥昔单抗联合化疗治疗转移性结直肠癌的护理

目的探讨西妥昔单抗联合化疗治疗转移性结直肠癌的护理方法。方法对20例转移性结直肠癌患者应用西妥昔单抗联合化疗进行治疗,化疗前给予心理护理,减轻患者焦虑,使其能较好地配合治疗;治疗期间重点做好不良反应的护理,预防及减轻不良反应的发生。结果治疗过程中1例患者出现西妥昔单抗过敏,1例出现肺水肿,经处理后好转,其余患者治疗均顺利进行。结论恰当的护理可预防和减轻西妥昔单抗不良反应的发生,确保治疗的顺利进行,提高治疗效果。     

56例大肠癌术后结肠镜随访检查结果分析

目的：观察大肠癌患根治性切除术后局部复发情况。方法：患术后每隔3个月，半年，1年及2年各作一次肠镜检查及病理组织活检，以观察肿瘤复发情况。结果：大肠癌术后1－2年为好发期，其局部复发与大肠癌原发部位，Dukes分明，组织学类型及分化程度有关，结论：大肠癌患术后都应该在无症状时进行定期的内镜随访检查，以期早期发现，早期治疗术后复发的肿瘤。     

大肠癌外周血循环肿瘤细胞数的检测及临床意义

目的 检测大肠癌（CRC）患者外周血循环肿瘤细胞（CTCs）数,探讨其临床意义.方法 58例CRC患者术前静脉采血,使用多重聚合酶链式反应（PCR）结合荧光定量PCR（RTFQ PCR）方法检测外周血细胞角蛋白20（CK20）及癌胚抗原（CEA） mRNA表达,比较CTCs细胞阳性率与临床病理参数的关系.结果 58例CRC患者外周血中CK20及CEAmRNA表达的阳性率为93.1％.CTCs的阳性检出率与Ducke＇s分期及淋巴结转移相关（P＜0.05）.结论 多重RTFQ PCR方法可应用于CRC患者外周血中CTCs检测,对预后判断有着重要的临床意义.     

SYBR Green Ⅰ实时荧光定量方法检测结直肠癌患者外周血CEA-mRNA表达研究

目的建立检测CEA mRNA表达水平的实时荧光定量逆转录聚合酶链反应（VQ-PCR）方法，探讨外周血CEA mRNA表达在结直肠癌患者中的应用价值。方法应用SYBR Green J作为荧光染料，以GAPDH作为内对照，建立检测CEA mRNA的FQ-PCR方法，并对56例结直肠癌患者外周血中CEA mRNA的表达水平进行了检测。结果56例结直肠癌患者中有33例外周血CEA mRNA表达为阳性，表达水平为1．07±2．99，阳性表达率为66．1％（37／56），30例结直肠良性疾病患者中有2例外周血CEA mRNA表达为阳性，表达水平为0．13±0．07，阳性表达率为6．7％（2／30），30例健康成人外周血CEA mRNA表达均为阴性；结直肠癌患者外周血CEA mRNA在不同病理分化程度中表达水平无明显变化（P〉0．05），但在Dukes C＋D期表达水平（1．73±2．15）及表达阳性率82．8％（24／29）均显著高于Dukes A＋B期表达水平（0．39±0．87）及表达阳性率48．1％（13／27）（P〈0．01）。结论该VQ-PCR方法简便、特异、可靠；检测外周血CEA mRNA表达水平，对诊断结直肠肿瘤病变比血清CEA蛋白具有更高的敏感性，可提高早期结直肠癌诊断符合率；在发生转移的Dukes C＋D期其表达水平及表达阳性率均显著高于未发生转移的Dukes A＋B期，可作为鉴别结直肠癌患者发生微转移的有力证据之一，动态观察其水平变化对判断结直肠癌患者的预后有重要价值。