血液系统肿瘤患者的营养治疗专家共识

血液系统肿瘤患者诊治过程中普遍存在营养不良，化疗作为血液系统肿瘤最重要的治疗手段，进一步加剧患者的营养不 良，其最主要的原因是化疗引起的恶心、呕吐及摄食减少。诱导治疗后C反应蛋白的显著升高，提示感染发生率及炎症水平均较高， 这在一定程度上可能干扰机体代谢、加剧营养状态的恶化。血液系统肿瘤患者的营养不良表现为体质指数异常、人体成分异常、整体/ 综合评估异常和生化指标异常。血液系统肿瘤患者营养治疗的原则与其他肿瘤类似，肠内营养为主，肠外营养为辅。但是，需要注意 补充特殊营养剂：①谷氨酰胺；②针对“粒细胞减少”的饮食；③ω‐3多不饱和脂肪酸；④牛初乳及大豆饮食。通过营养筛查和评估，为 处于不同治疗阶段的血液系统肿瘤患者制定营养治疗方案，及时、恰当地进行个体化营养治疗，可显著改善血液系统肿瘤患者营养状 况、预防营养不良及相关并发症，降低治疗相关不良反应风险，提高耐受性、疗效及生活质量。     

Immune microenvironment of hepatocellular carcinoma,intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma: Relationship with histopathological and molecular classifications

Tumor tissue is composed of tumor cells and tumor stroma. Tumor stroma contains various immune cells and non-immune stromal cells, forming a complex tumor microenvironment which plays pivotal roles in regulating tumor growth. Recent successes in immunotherapies against tumors, including immune checkpoint inhibitors, have further raised interests in the immune microenvironment of liver carcinoma. The immune microenvironment of tumors is formed because of interactions among tumor cells, immune cells and non-immune stromal cells, including fibroblasts and endothelial cells. Different patterns of immune microenvironment are observed among different tumor subtypes, and their clinicopathological significance and intertumor/intratumor heterogeneity are being intensively studied. Here, we review the immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma, focusing on its histopathological appearance, clinicopathological significance, and relationship with histological and molecular classifications. Understanding the comprehensive histopathological picture of a tumor immune microenvironment, in addition to molecular and genetic approaches, will further potentiate the effort for precision medicine in the era of tumor-targeting immunotherapy.     

Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

术中目标导向液体治疗在腹膜后巨大恶性肿瘤切除术患儿中的应用

目的:探讨基于脉压变异度（PPV）的目标导向液体治疗（GDFT）在腹膜后巨大恶性肿瘤切除术患儿中的应用。方法:择期行腹膜后巨大恶性肿瘤切除术患儿64例，年龄0.5~3岁，ASA Ⅱ-Ⅲ级。随机将患儿分为目标导向液体治疗组（G组）和常规液体治疗组（C组），每组32例。G组以PPV为指导，根据GDFT方案进行液体管理，C组采用常规液体管理。记录手术开始（T1）、手术开始后1 h（T2）、手术结束（T3）的MAP、CVP、PPV、Lac值、TNF-α、IL-6浓度。记录术中输注晶体液量、胶体液量、液体总量、出血量、尿量、手术时间、多巴胺使用率以及排气时间、术后住院时间和恶心呕吐发生率。结果:G组输注晶体液量显著少于C组（P＜0.05），而输注胶体液量显著多于C组（P＜0.05）。两组术中输注液体总量、出血量、尿量与多巴胺使用率方面差异无统计学意义。T2、T3时刻，G组PPV、TNF-α、IL-6显著低于C组（P＜0.05），而两组间MAP、CVP、Lac在各时点差异无统计学意义。G组术后排气时间明显短于C组（P＜0.05），而在术后恶心呕吐发生率和住院时间方面两组差异无统计学意义。结论:PPV指导的GDFT可以应用于腹膜后巨大恶性肿瘤切除术患儿，能维持其血流动力学稳定，减少炎症因子IL-6、TNF-α释放，促进胃肠功能恢复，但对术后转归无明显影响。     

Z形皮瓣及推进皮瓣修复眼睑缺损的作用探讨

目的探讨眼睑恶性肿瘤切除术中应用Z形皮瓣及推进皮瓣I期修复眼睑缺损的临床效果。方法将50例眼睑恶性肿瘤切除术患者按不同缝合方法分为两组,即对照组25例,术中直接缝合;观察组25例,术中行Z形皮瓣及推进皮瓣I期修复;比较两组眼睑修复效果。结果观察组术后皮瓣成活率96.0%、切口Ⅰ期愈合率100%、修复满意率92.0%,均高于对照组的72.0%、68.0%、56.0%,差异有统计学意义(P<0.05)。观察组术后并发症发生率低于对照组,但差异无统计学意义(P>0.05)。结论眼睑恶性肿瘤切除术中眼睑缺损修复时,采用Z形皮瓣及推进皮瓣,眼睑修复良好,患者修复满意率高,值得推广应用。     

Defining the dimensions of circulating tumor cells in a large series of breast,prostate, colon,and bladder cancer patients

Circulating tumor cells (CTCs) in the blood of cancer patients are of high clinical relevance. Since detection and isolation of CTCs often rely on cell dimensions, knowledge of their size is key. We analyzed the median CTC size in a large cohort of breast (BC), prostate (PC), colorectal (CRC), and bladder (BLC) cancer patients. Images of patient‐derived CTCs acquired on cartridges of the FDA‐cleared CellSearch^® method were retrospectively collected and automatically re‐analyzed using the accept software package. The median CTC diameter (μm) was computed per tumor type. The size differences between the different tumor types and references (tumor cell lines and leukocytes) were nonparametrically tested. A total of 1962 CellSearch^® cartridges containing 71 612 CTCs were included. In BC, the median computed diameter (CD) of patient‐derived CTCs was 12.4 μm vs 18.4 μm for cultured cell line cells. For PC, CDs were 10.3 μm for CTCs vs 20.7 μm for cultured cell line cells. CDs for CTCs of CRC and BLC were 7.5 μm and 8.6 μm, respectively. Finally, leukocytes were 9.4 μm. CTC size differed statistically significantly between the four tumor types and between CTCs and the reference data. CTC size differences between tumor types are striking and CTCs are smaller than cell line tumor cells, whose size is often used as reference when developing CTC analysis methods. Based on our data, we suggest that the size of CTCs matters and should be kept in mind when designing and optimizing size‐based isolation methods.

Abbreviations

ACCEPT

Automated CTC Classification, Enumeration, and PhenoTyping software

BC

breast cancer

BLC

bladder cancer

CD

computed diameter

CEL

cultured tumor cell (cell line)

CK

cytokeratin

CRC

colorectal cancer

CTC‐L

circulating tumor cells derived from cerebrospinal fluid (liquor)

CTCs

circulating tumor cells

DAPI

4′6‐diamidino‐2‐phenylindole

EMT

epithelial–mesenchymal transition

EpCAM

epithelial cell adhesion molecule

IQR

interquartile range

KW test

Kruskal–Wallis test

MWU test

Mann–Whitney U test

NCR

nucleus/cytoplasm ratio

P2A

perimeter to area

PC

prostate cancer

TIF

tagged Image Format files

TXT

text file

μm

micrometer

µm²

square micrometers

     

基于外邪理论探讨肿瘤的发病机制

肿瘤防控是当今世界性一大难题，目前我国每年新发肿瘤病例即将突破400万。近年来，我国肿瘤总体发病率和死亡率呈现逐年上升趋势，肿瘤的高死亡率和低治愈率已严重威胁我国居民健康，很大程度影响了患者的生存质量，大大降低患者的生活水平，危害患者的身心健康。中医认为，肿瘤发病的病因复杂，病机变化多端，是内外因相互影响、相互作用的结果。若在外邪作用于人体之初，及时辨证施治，防止伏邪入里发生传变，将大大减少肿瘤疾病的发生和发展。因此，外邪理论与肿瘤的发病机制亟待进一步探究。在中国知网（CNKI），Public Medline（PubMed）数据库中以外感、邪气、中医、肿瘤、发病机制等关键词进行检索，本文共纳入67篇中英文文献为参考，对外邪理论与肿瘤发病机制进行全面探讨。强调了外邪在肿瘤发病中的重要作用，以及中医药在早期防治肿瘤中具有显著的优势。外邪如风邪、寒邪、湿邪、火邪、从口鼻皮表而入的邪气等因素，使得肿瘤的发生更具复杂性。中医药可以在肿瘤发展早期进行有效的防护和干预，可大大提高防病抗肿瘤的目的，减少肿瘤的发生、发展、传变，使临床用药更有效、更精准、更具靶向性，不至使肿瘤的治疗错失良机，为临床治疗肿瘤提供更明确的指导方向。     

Oncentra近距离计划系统和MIM系统间DVH参数差异的分析

目的对近距离治疗计划的剂量参数在Oncentra治疗计划系统与MIM系统间产生的差异进行分析和研究。方法选取本院的43例妇科肿瘤患者近距离治疗计划,按照临床要求所有病例的靶区D₉₀达到处方剂量。评估参数包括:靶区体积和D₉₀,处方剂量总体积,靶区内的处方剂量体积以及危及器官包括:直肠,膀胱,小肠的D_0.01cc,D_1cc,D_2cc。结果计划系统中的靶区体积和处方剂量值均明显小于MIM系统中相应的值(P<0.05),两系统显示出的处方体积相差不大。MIM系统中的靶区D₉₀(676.74±54.82)cGy小于处方剂量,危及器官的受量则正好相反,即计划系统比MIM系统中相应的参数要小,其中直肠和膀胱的D_0.01cc,D_1cc,D_2c,小肠的D_0.01cc,D_2cc的在两系统显示的值的差异均有统计学意义(P<0.05)。结论不同系统间传输相同的剂量和轮廓文件,DVH参数存在一定的差异,其主要原因是在不同系统对已勾画的各种器官轮廓计算体积存在算法上的不同。基于此,建议近距离计划在CT扫描时,尽量小的层厚可以消除或减少这种差异。