乳腺癌患者心理社会因素与免疫功能的相关性

免疫系统在肿瘤进展中有重要作用,心理社会因素也会影响肿瘤的发生、发展。乳腺癌相关心理社会因素主要包括应激性生活事件、应对方式、情绪和个性特征以及社会支持。相关免疫应答效应因素包括T淋巴细胞及其亚群等特异性免疫,TNF-a、巨噬细胞、NK细胞等非特异性免疫应答效应因素。探讨乳腺癌患者心理、肿瘤、免疫之间的关系,作为乳腺癌心理治疗的基础,具有重要意义。     

多西紫杉醇联合GP化疗方案对晚期非小细胞肺癌患者炎性因子、免疫功能及临床症状的影响

目的 探讨多西紫杉醇联合吉西他滨+顺铂(GP)化疗方案对晚期非小细胞肺癌患者炎性因子、免疫功能及临床症状的影响.方法 回顾性分析40例晚期非小细胞肺癌患者的临床资料,所有患者均接受多西紫杉醇联合GP化疗方案,化疗2个周期后,比较化疗前后患者的血清炎性因子、免疫功能及临床症状.结果 化疗2个周期后,患者的血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、C-反应蛋白(CRP)浓度明显低于化疗前(P﹤0.01);CD3+、CD4+、CD4/CD8水平高于化疗前,CD8+水平低于化疗前,差异均有统计学意义(P﹤0.05);癌因性疲乏、局部疼痛及食欲不振评分均明显低于化疗前(P﹤0.01).结论 多西紫杉醇联合GP化疗方案能有效缓解晚期非小细胞肺癌患者的临床症状,可能与降低血清炎性因子水平、改善免疫功能等因素有关.     

卡培他滨辅助化疗联合TP方案同步放化疗对中晚期食管癌患者免疫功能及炎性因子的影响

目的探讨卡培他滨辅助化疗联合紫杉醇+顺铂(TP方案)同步放化疗对中晚期食管癌患者免疫功能和炎性因子水平的影响。方法根据治疗方案的不同,将160例中晚期食管癌患者分为对照组(n=76)和观察组(n=84),对照组患者接受TP方案同步放化疗,观察组患者在此基础上联合卡培他滨辅助化疗。比较两组患者治疗前和治疗后6个月血清免疫球蛋白[免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、免疫球蛋白G(IgG)]水平和炎性因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)]水平。结果治疗前,两组患者血清免疫球蛋白和炎性因子水平比较,差异均无统计学意义(P﹥0.05)。治疗后,观察组患者IgA、IgG和IgM水平均明显高于本组治疗前和对照组患者(P<0.01);治疗后,两组患者血清TNF-α、IL-6和IL-8水平均明显低于本组治疗前,且观察组患者血清TNF-α、IL-6和IL-8水平均明显低于对照组患者,差异均有统计学意义(P<0.01)。结论卡培他滨辅助化疗联合TP方案同步放化疗治疗食管癌,可有效恢复患者免疫功能,改善机体炎性状态,提高临床疗效。     

胃肠道肿瘤患者围化疗期营养状况的评价及对免疫功能的影响

目的:运用患者主观全面评价法(patient generated-subjective global assessment,PG-SGA)和营养风险筛查2002(nutrition risk screening 2002,NRS-2002)并结合实验室指标对围化疗期胃肠道肿瘤患者进行营养评价及免疫功能检测,观察营养不良及营养风险对相关临床指标的影响。方法:收集2012年2月至2014年2月期间于我院诊断为胃肠道恶性肿瘤术后待化疗患者80例,通过PG-SGA评分、NRS-2002评分、体格测量及实验室检测进行营养评价。检测T细胞亚群（CD4+、CD8+、CD4+/CD8+）。以PG-SGA评分作为营养评价指标,将80例化疗前患者分为A组（0-3分）、B组（4-8分）和C组（＞8分）,分别测定外周血T淋巴细胞亚群。其中资料完整的45例化疗患者于化疗6周期后重复上述内容,并观察化疗后并发症、平均住院时间。结果:PG-SGA评价结果为营养不良者占68.75%,NRS-2002评价结果营养不良者占42.50%。PG-SGA与NRS-2002分别与其他营养评价指标评价结果间均有显著相关性（P＜0.05）。随着营养不良评分的升高,CD4+和CD4+/CD8+均呈不同程度下降,差异有统计学意义（P＜0.05）。PG-SGA评分与CD4+之间的相关系数r=－0.399(P＜0.01);PG-SGA与CD4+/CD8+之间的相关系数r=－0.655(P＜0.01)。胃肠道肿瘤患者化疗后营养不良发生率高于化疗前。化疗后与化疗前,CD4+/CD8+明显下降,差异有显著性（P＜0.05）。化疗后营养不良组与营养良好组相比平均住院时间及并发症发生率显著增高（P＜0.05）。与无营养风险组相比,存在营养风险组的平均住院时间及并发症发生率显著增高（P＜0.05）。结论:联合运用PG-SGA、NRS-2002和实验室检测指标有助于提高肿瘤患者营养不良的诊断率。     

癌痛对抑郁及免疫功能的影响

目的:分析癌痛与抑郁和免疫功能之间的相关性。方法:收集我科室从2013年1月至2016年12月收治的73例晚期肿瘤患者,37例癌痛组,36例无癌痛组,进行数字疼痛强度量表(NRS)、抑郁自评量表(SDS)、生活质量、免疫功能等的调查分析比较。结果:癌痛与无癌痛的两组患者抑郁的发生比较有统计学意义(P＜0.05),癌痛程度与抑郁程度有相关性(P＜0.05);癌痛与无癌痛的两组患者生活质量的比较差异有统计学意义(P＜0.05)。癌痛与无癌痛的两组患者CD3+、CD4+、CD8+比较差异无明显统计学意义(P＞0．05)。结论:抑郁的发生与癌痛相关,抑郁程度和癌痛程度也有极大关联。癌痛可明显影响患者生活质量,但对免疫功能影响不明显。     

乌司他丁对食管癌手术患者CD14+肺泡巨噬细胞及免疫功能的影响

目的:探讨术前静脉输注乌司他丁对食管癌手术患者单肺通气时CD14+肺泡巨噬细胞、局部及全身炎性反应和免疫功能的影响。方法:前瞻性选取南京医科大学附属肿瘤医院2019年10月至2020年8月行胸腔镜下食管癌根治手术患者80例,数字随机表法分为两组:对照组和乌司他丁组各40例。乌司他丁组患者麻醉诱导前静脉输注20 KU乌司他丁,对照组给予生理盐水。检测两组患者术前和术后2 h外周静脉中血白介素-2（IL-2）和免疫细胞,并检测术中单肺通气1 h后非通气侧肺支气管肺泡灌洗液（bronchoalveolar lavage fluid,BALF）中CD14+巨噬细胞、IL-2、免疫细胞。结果:两组患者一般情况比较无差异。术后2 h乌司他丁组患者外周血中IL-2、CD14+单核细胞增高幅度小于对照组,差异有统计学意义（P＜0.05）,NK细胞、CD4+T细胞、CD8+T细胞及活化的T细胞亚群增高幅度高于对照组,差异有统计学意义（P＜0.05）。两组患者术前外周血IL-2、CD14+单核细胞及主要免疫细胞亚群差异无统计学意义（P>0.05）。与对照组相比,乌司他丁组患者单肺通气1 h后非通气侧肺BALF中IL-2和CD14+巨噬细胞增高幅度明显小于对照组,差异有统计学意义（P＜0.05）,而CD4+T细胞、CD8+T细胞高于对照组,差异有统计学意义（P＜0.05）,活化的T细胞也高于对照组,差异有统计学意义（P＜0.01）。结论:麻醉前给予乌司他丁能减少食管癌术中单肺通气时全身及肺部的炎性反应,保护患者的免疫功能,具有临床应用价值。     

肠内免疫营养与全素营养疗法在胃肠道肿瘤患者术后护理中的应用效果比较

目的探讨肠内免疫营养在胃肠道肿瘤患者术后的应用效果。方法将86例胃肠肿瘤患者分为术后予以肠内免疫营养疗法的观察组和行全素营养疗法的对照组,观察两组患者的营养状况、生化指标以及随访3个月的生活质量。结果两组患者经不同营养干预后,观察组不仅营养状况指标而且微型营养评估法（MNA）、体重指数（BMI）、血清蛋白（ALB）及血红蛋白（HBG）等均优于对照组,差异均有统计学意义（均P〈0．05）。3个月随访结果表明观察组各项生活质量指标均优于对照组,差异有统计学意义（P〈0．05）。结论胃肠肿瘤患者术后予以肠内免疫营养治疗,不仅可有效改善患者的营养状况,而且可提高生活质量。     

乳腺癌患者心理社会因素与免疫功能的相关性

免疫系统在肿瘤进展中有重要作用,心理社会因素也会影响肿瘤的发生、发展.乳腺癌相关心理社会因素主要包括应激性生活事件、应对方式、情绪和个性特征以及社会支持.相关免疫应答效应因素包括T淋巴细胞及其亚群等特异性免疫之间的关系,作为乳腺癌心理治疗的基础,具有重要意义.     

Increased apoptosis is associated with robust immune cell infiltration and cytolytic activity in breast cancer

Tumor infiltrating immune cells plays a critical role in cancer progression. Apoptosis is an autonomous cell death that counteracts tumor growth. To this end, we hypothesized that increased apoptosis in breast cancer is associated with immune cell killing. Apoptosis score of MSigDB Hallmark collection was used to analyze METABRIC cohort (n=1904) and TCGA (n=1069) as validation cohort. High apoptosis tumors enriched cancer promoting signaling pathways; hypoxia, KRAS, TGF-β, PI3K signaling, and was associated with low MKI67 expression and less cell proliferation gene sets, less homologous recombination defects, and less altered fraction. High apoptosis tumors also enriched angiogenesis and high infiltration of vascular endothelial cells, pericytes and stromal cells and significantly enriched inflammation and immune response-related gene sets and high infiltration of CD8, CD4 memory, dendritic cells, M1 and M2 macrophages and significant elevation of cytolytic activity and immune checkpoint molecules, consistently in both cohorts. In conclusion, breast cancer patients with high apoptosis are associated with angiogenesis, immune response, high immune cell infiltration and cytolytic activity. To the best of our knowledge, this is the first study to utilize in silico translational approach to demonstrate the clinical relevance of apoptosis in breast cancer patients in large cohorts.     

Relationship of stress management skill to psychological distress and quality of life in adults with cancer

Background: Distress is common among cancer patients, especially those undergoing chemotherapy. Although skill in stress management is often the target of intervention efforts, its relationship to distress and quality of life in patients about to begin cancer treatment has not been examined. Objective: To examine the relationship of pre‐treatment skill in stress management to patient distress and quality of life. Methods: One hundred and ten adults diagnosed with stage I–IV cancer and ECOG?2 provided data on perceived stress management skill, anxiety, depression, and health‐related quality of life prior to their initial chemotherapy infusion. Results: As predicted, greater skill in stress management was associated with lower levels of anxiety and depression and better overall mental quality of life. These relationships were generally independent of demographic and clinical variables also found to be associated with distress and quality of life. Conclusions: Findings confirm that skill in stress management is related to pre‐chemotherapy distress and quality of life and suggest the importance of assessing this variable as part of efforts to link distressed patients to appropriate psychosocial services. Findings also raise the possibility that assessing extant stress management skills could be used to match patients to the type of intervention most likely to benefit them. Copyright © 2009 John Wiley & Sons, Ltd.     

重视肿瘤疫苗的临床免疫反应监测

免疫细胞的激活是肿瘤疫苗治疗后的第一个生物学事件,标志着肿瘤免疫应答的产生,因此在临床上监测能反映免疫细胞激活状态的免疫指标对肿瘤疫苗的临床应用非常有意义。目前已建立了多种针对临床免疫反应的监测方法,但它们的重复性和可比性还面临挑战,尚缺乏可作为金标准的质量控制措施,它们与临床反应的关系还尚待大样本的临床验证;另外,免疫相关不良反应和肿瘤抗原的扩展也增加了免疫指标判定的复杂性。最近几年,一些国际学术组织制定了免疫反应监测的评价标准,提出了关于T细胞监测最少信息的计划;美国FDA公布的肿瘤疫苗临床使用指南,对疫苗免疫反应监测也提出了一系列指导性意见。目前国内业界对肿瘤疫苗的临床免疫反应监测尚缺乏足够的重视,已开展的监测工作不够规范。本文对肿瘤疫苗的免疫反应监测所面临的问题和挑战进行了分析,就国内业界如何重视和加强肿瘤疫苗临床免疫反应监测的基础研究和临床试验提出了若干建议,以期在不久的将来,我国该领域的工作能迎头赶上国际先进水平。     

复方苦参注射液辅助治疗对晚期肿瘤患者骨转移疼痛及免疫功能的影响

目的:观察复方苦参注射液辅助治疗对晚期肿瘤患者癌痛及免疫功能的影响。方法:80例癌症患者随机分成治疗组和对照组各40例,治疗组给予复方苦参注射液联合常规盐酸羟考酮缓释片;对照组单用盐酸羟考酮缓释片。结果:治疗组缓解率为38例(95.0%)高于对照组31例(77.5%)(P<0.05),两组治疗前的体液免疫、细胞免疫,焦虑自评量表(SAS)评分和抑郁自评量表(SDS)评分均无显著差异(P>0.05),治疗后,与对照组比,观察组的体液免疫和细胞免疫明显增高(P<0.05),SAS和SDS明显降低(P<0.05)。两组均无失访案例,随访时间2~40个月,对照组存活20例,中位生存时间为19个月,观察组存活30例,中位生存时间为20个月,与对照组比,观察组的生存时间明显延长（P=0.033)。结论:复方苦参注射液治疗癌痛的疗效肯定,并可缓解患者的焦虑抑郁,改善免疫情况。     

Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer

Background:

The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact.

Methods:

Using immunohistochemistry, we examined tumour-infiltrating CD68⁺ pan-macrophages, HLA-DR⁺CD68⁺ M1 macrophages (M1), CD163⁺ or CD204⁺ M2 macrophages (M2), CD66b⁺ neutrophils (Neu), CD4⁺ T cells (CD4⁺T), CD8⁺ T cells (CD8⁺T), and FOXP3⁺CD4⁺ regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan–Meier method and Cox proportional hazards model.

Results:

Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4⁺T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4⁺T, CD8⁺T, or the ratio of M1 to pan-macrophages (%M1) were significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4⁺T^high/CD8⁺T^high/%Treg^low and tumour-infiltrating %M1^high/M2^low. Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio.

Conclusion:

Tumour-infiltrating CD4⁺T^high/CD8⁺T^high/%Treg^low and %M1^high/M2^low are independent prognosticators useful for evaluating the immune microenvironment of PDC.     

盐酸右美托咪定对肺癌患者术后镇痛效果及机体免疫功能的影响

目的探讨盐酸右美托咪定在肺癌手术患者术后镇痛中的效果及对机体免疫功能的影响。方法选取148例接受胸腔镜肺癌根治术治疗患者,依据随机数字表法分为观察组和对照组,每组74例。对照组患者接受瑞芬太尼+昂丹司琼镇痛治疗,观察组患者在此基础上联合右美托咪定镇痛治疗。手术前及术后6、12、24、48 h,采用视觉模拟评分法(VAS)评估两组患者的疼痛程度;手术前后,比较两组患者T淋巴细胞亚群(CD3+、CD4+、CD8+、CD4+/CD8+)、γ-干扰素(IFN-γ)和白细胞介素-10(IL-10)水平的变化情况。结果术后6、12、24、48 h,观察组患者的VAS评分均明显低于对照组患者,差异均有统计学意义(P﹤0.01)。手术后,观察组患者IFN-γ、CD3+、CD4+、CD8+及CD4+/CD8+水平均明显低于本组手术前,IL-10水平明显高于本组术前,且观察组患者IFN-γ水平明显低于对照组患者,IL-10、CD3+、CD4+及CD4+/CD8+水平均明显高于对照组患者,差异均有统计学意义(P﹤0.01)。两组患者恶心、呕吐、嗜睡及心动过缓等不良反应发生率比较,差异均无统计学意义(P﹥0.05)。结论盐酸右美托咪定对肺癌术后患者的镇痛效果较好,能够在一定程度上改善患者免疫功能,且不增加不良反应。     

The impact of clinical guidelines on surgical management in patients with thyroid cancer

Aims: Thyroid cancer is an uncommon but highly curable disease if treated optimally. The aim of this study was to determine whether clinical guidelines introduced locally at the beginning of 1999 were associated with better surgical outcome, using radioiodine uptake as a surrogate measure of completeness of thyroidectomy.Materials and methods: We reviewed the medical records of all patients with thyroid cancer referred to a cancer centre (n=176) 3 years before and 3 years after the introduction of guidelines. The uptake of radioiodine in the thyroid bed after thyroidectomy and before radioiodine ablation was used to assess the completeness of primary surgical treatment.Results: The number of new cases referred to our centre increased from 80 in the 1996–1998 period to 94 during 1999–2001. This was largely because of an excess of papillary thyroid cancers. Documentation in the medical records of the pathological primary tumour size improved from 47.5% to 80.8% following the introduction of guidelines. A significant reduction in radioiodine uptake in the thyroid bed was observed following the introduction of guidelines (5.03%±6.82 (SD) vs 2.75%±5.10 (SD); P=0.005). Linear regression analysis of clinical variables indicated that the year of surgery was the only significant factor influencing radioiodine uptake in the thyroid bed (P=0.014). Twelve hospitals within the Northern Cancer Network carried out thyroid surgery for thyroid cancer in the pre-guideline era compared with seven hospitals in the post-guideline era. Surgeons who were members of the regional multidisciplinary thyroid cancer team operated on 35% of cases in the 1996–1998 period and 56.4% in the 1999–2001 period (P<0.01).Conclusions: The introduction of clinical guidelines in 1999 was associated with a reduction in the size of thyroid remnant after primary surgical treatment. This was accompanied by fewer hospitals undertaking thyroid surgery and more patients being operated on by surgeons who were members of the thyroid cancer multidisciplinary team.     

进展期胃癌病人脾脏免疫功能状态的研究

目的探讨进展期胃癌患者脾脏的免疫状态.方法检测正常人及进展期胃癌患者共35例脾静脉血和外周静脉血进行T细胞亚群、自然杀伤细胞(NK细胞)活性、循环免疫复合物测定.结果(1)与正常人外周血淋巴细胞(PBL)相比,进展期胃癌患者的PBL、脾静脉血淋巴细胞(SVL)的NK细胞活性及CD+3、CD+4细胞降低,CD+8细胞增多,使CD+4/CD+8比值下降.(2)从进展期胃癌患者PBL.SVL比较结果可见,后者NK细胞活性、CD+4/CD+8细胞比值明显低于PBL.(3)进展期胃癌患者SVL的循环免疫复合物(CIC)水平高于其PBL,也高于正常人PBL.结论进展期胃癌患者脾脏不但未能起正性免疫作用,且逐步转向负性免疫状态.     

右旋美托咪定对肝癌患者手术应激反应的影响

目的:观察右旋美托咪定能否有效调控肝癌患者手术的应激反应.方法:选择肝癌手术患者60例,年龄30～ 60岁,ASAⅡ-Ⅲ级,随机分为D组和C组.一组注射器内放入200μg的右旋美托咪定,一组使用生理盐水作为对照组,配制和标记均由不参与本实验的麻醉医生完成.两组均在麻醉诱导前15min内给予试验药物负荷剂量0.4μg/kg,并随后以0.2μg·kg-1 h-1的速度持续静脉输注.记录患者麻醉前(T0)、插管前即刻(T1)、插管后即刻(T2)、切皮即刻(T3)、术中探查(T4)、拔管即刻(T5)的平均动脉压(MAP)和心率(HR),并在T0、T2、T4、T5时刻抽取静脉血标本,检测血糖、肾上腺素和去甲肾上腺素水平;记录睁眼时间、拔管时间以及术后30 min(T6)和术后60min(T7)的Aldrete评分;记录术后躁动的发生率和术后要求镇痛的人数.结果:C组T2、T5时HR、MAP较T0有明显升高,而D组仅轻度升高,组间有显著差异(P＜0.05);两组所测肾上腺素和去甲肾上腺素水平均增高,但C组显著增高(P＜0.05);血糖水平T4、T5时刻D组比C组低(P＜0.05);D组术后发生躁动和要求镇痛的人数少于C组(P＜0.05).结论:右旋美托咪定能有效控制肝癌手术术中血压和心率的波动,并有效调控机体儿茶酚胺和血糖水平,降低机体的应激反应,并且不影响术后苏醒时间,提高肝癌患者术后的舒适度.     

肝癌患者红细胞免疫功能检测及评价

目的:研究肝癌患者红细胞免疫功能变化的规律.方法:采用郭峰法测定45例肝癌患者及45例正常对照人群的红细胞免疫功能.结果:肝癌患者红细胞免疫功能明显下降,红细胞C3b受体花环率(RBC-C3bRR)、肿瘤红细胞花环(RBC-CaR) 显著低于正常对照组,而红细胞免疫复合物花环率(RBC-ICR)显著高于对照组(P＜0.05).结论:原发性肝癌患者存在红细胞免疫功能障碍,因此在免疫治疗中,应加强红细胞免疫功能的调节和恢复.