Gastrointestinal stromal tumor metastasis at the site of a totally implantable venous access port insertion:A rare case report

BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the insertion of a TIVAP is extremely rare.CASE SUMMARY We report the case of 33-year-old male with advanced gastrointestinal stromal tumor(GIST)who underwent radical tumor resection after neoadjuvant imatinib therapy.However,a solitary GIST metastasis at the site of a TIVAP insertion developed during adjuvant imatinib treatment.Mutational analysis showed secondary mutation in KIT exon 13(V564 A),which is resistant to imatinib treatment.To our knowledge,this is the first case report of a patient with advanced GIST developing GIST metastasis at the site of a TIVAP insertion.CONCLUSION This case highlights that when a patient with advanced,high metastatic GIST requires TIVAP insertion,we should realize that there is a risk of developing tumor metastasis at the site of a TIVAP insertion.

Health-related quality of life evaluated by tumor node metastasis staging system in patients with hepatocellular carcinoma

AIM: To investigate and evaluate the change in healthrelated quality of life (HRQoL) by tumor node metastasis (TNM) staging system in patients with hepatocellular carcinoma (HCC). METHODS: A total of 140 patients diagnosed with HCC between June 2008 and April 2009 in our department were enrolled to this study. One hundred and thirty-five (96.5%) patients had liver cirrhosis secondary to hepatitis B virus (HBV) infection, 73 (54.07%) of them being HBV DNA positive; the other etiologies of liver cirrhosis were alcoholic liver disease (1.4%), hepatitis C (1.4%) or cryptogenic (0.7%). All subjects were fully aware of their diagnosis and provided informed consent. HRQoL was assessed before treatment using the functional assessment of cancer therapy-hepatobiliary (FACT-Hep) questionnaire. Descriptive statistics were used to evaluate demographics and disease-specific characteristics of the patients. One-way analysis of variance and independent samples t tests were used to compare the overall FACT-Hep scores and clinically distinct TNM stages. Scores for all FACT-Hep items were analyzed by frequency analyses. The mean scores obtained from the FACT-Hep in different Child-Pugh classes were also evaluated. RESULTS: The mean FACT-Hep scores were reduced significantly from TNM StageⅠto Stage Ⅱ, Stage ⅢA, Stage ⅢB group (687 ± 39.69 vs 547 ± 42.57 vs 387 ± 51.24 vs 177 ± 71.44, P = 0.001). Regarding the physical and emotional well-being subscales, scores decreased gradually from Stage Ⅰ to Stage ⅢB (P = 0.002 vs Stage Ⅰ; P = 0.032 vs Stage Ⅱ; P = 0.033 vs Stage ⅢA). Mean FACT-Hep scores varied by Child-Pugh class, especially in the subscales of physical well-being, functional well-being and the hepatobiliary cancer (P = 0.001 vs Stage I; P = 0.036 vs Stage Ⅱ; P = 0.032 vs Stage ⅢA). For the social and family well-being subscale, only Stage ⅢB scores were significantly lower as compared with Stage Ⅰ scores (P = 0.035). For the subscales of functional well-being and hepatobiliary cancer, there were significant differences for Stages ⅡΙ, ⅢA and ⅢB (P = 0.002vs StageⅠ). CONCLUSION: HRQoL of patients with HCC worsens gradually with progression of TNM stages. The most impaired subscales of HRQoL, as measured by FACT-Hep, were physical and emotional well-being.

朱永康治疗分化型甲状腺癌术后并发症的经验

介绍朱永康教授治疗分化型甲状腺癌(DTC)术后并发症的临床经验。认为DTC术后的中医治疗分为早期和远期两个阶段,早期重在治“虚”,远期治疗除缓解其他治疗带来的毒副作用外,将“伏邪”理论引入治疗中,同时注重既病防变、已病防传和病愈防复。并附验案1则。

基于“态靶辨证”和肝脏病机要素探讨肿瘤肝转移的防治内涵

态靶辨证是由仝小林院士提出的临床辨治模式,通过结合宏观辨证与微观辨证,建立全程、动态、连续的疾病认识,并指导中医药的精准化治疗。肿瘤肝转移的生物学过程十分复杂,目前缺乏对其动态的病机变化认识。总结肿瘤肝转移的动态变化病机为郁→虚→瘀→积→损,通过宏观认识肝转移初始期、前期、中期、末期的“态”,提出以养血调肝为核心的扶正调态手段。在肿瘤肝转移的现代医学研究基础上,提出中药(如消癌解毒药、活血消癥药、行气化痰散结药等)微观靶向性治疗,形成全方位的态靶结合肿瘤肝转移防治策略,对中医药精准化防治肝转移具有一定的指导意义。

Biomimetic“Gemini nanoimmunoregulators”orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)degradation.The“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 peptides.mPDA/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity.Meanwhile,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion.Subsequently,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes.This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis.This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

谷氨酰胺代谢相关蛋白在肿瘤转移中的作用研究进展

肿瘤转移是导致癌症患者高死亡率的主要原因。谷氨酰胺在肿瘤的恶性进展中发挥重要作用,近年来研究发现,谷氨酰胺与肿瘤转移密切相关,谷氨酰胺作为肿瘤细胞重要的碳源和氮源,不仅影响肿瘤细胞的增殖,还参与调控肿瘤细胞的迁移和侵袭。此外,谷氨酰胺代谢过程中的各种酶及转运体通过不同的信号转导通路参与肿瘤转移过程。本文综述近年来谷氨酰胺在肿瘤转移中作用的研究进展,并梳理有关治疗靶点,以期为临床治疗肿瘤转移提供新的策略。

扶正祛邪法对肿瘤相关巨噬细胞的影响

肿瘤相关巨噬细胞具备的双向分化潜能,由于其异质性及在肿瘤生长代谢及肿瘤侵袭转移过程中发挥关键性作用,使得肿瘤相关巨噬细胞成为目前抗肿瘤治疗的重要靶点。“扶正祛邪”中医理论是治疗肿瘤的基本法则,关于“扶正祛邪”法则调节机体肿瘤相关巨噬细胞研究成为人们关注的热点。此文从具有“扶正祛邪”功效的中医药抗肿瘤的基本理论出发,综述近年国内外相关文献。探讨“扶正祛邪”法则调节机体肿瘤微环境下肿瘤相关巨噬细胞的作用,为中医药抗肿瘤的临床治疗、基础研究及中药新药的研发提供一定的思路。

安罗替尼联合卡培他滨/替莫唑胺方案后线治疗SCLC脑转移患者的疗效和安全性研究

目的评价安罗替尼(Anlotinib)联合卡培他滨/替莫唑胺(CAPTEM)方案在晚期小细胞肺癌(SCLC)脑转移患者后线治疗中的疗效及安全性。方法纳入2018年8月至2021年8月在成都市龙泉驿区第一人民医院二线化疗后进展脑转移的SCLC患者23例,后线治疗方案予Anlotinib靶向治疗联合CAPTEM方案抗肿瘤治疗。观察患者的无进展生存时间(PFS)、颅内无进展生存时间(iPFS)、客观缓解率(ORR)、疾病控制率(DCR)、颅内客观缓解率(iORR),并进行单因素分析;采用COX多因素回归分析纳入患者的PFS和iPFS;采用Kaplan-Meier法进行相关数据的生存分析,评估该联合方案对晚期SCLC脑转移患者后线治疗的疗效及安全性。结果疗效分析:23例患者中完全缓解0例,部分缓解10例,病情稳定10例,疾病进展3例;ORR为43.47%,DCR为86.95%。脑转移评估:23例患者中完全缓解0例,部分缓解11例,病情稳定10例,疾病进展2例,iORR为47.82%。患者中位PFS为6.4(5.4,7.0)个月,iPFS为6.5(5.5,7.4)个月。单因素分析:吸烟等不良生活方式、体力状况美国东部肿瘤协作组(ECOG)评分标准评分、同步颅内转移灶放疗对患者的PFS有一定影响(P<0.05),而体力状况ECOG评分、同步颅内转移灶放疗与患者的iPFS有关(P<0.05)。多因素分析:体力状况ECOG评分对患者的PFS及iPFS均具有显著影响(P<0.01)。23例患者未出现4级不良反应事件,发生常见不良反应为手足综合征[30.43%(7/23)]、口腔黏膜炎[17.39%(4/23)]、高血压[26.08%(6/23)]、胃肠道反应[30.43%(7/23)]、食欲减退[21.73%(5/23)]、腹泻[13.04%(3/23)]等,均为1~2级;1例患者出现高血压3级不良事件,予高血压药物后控制良好,调整剂量后反应良好;所有患者无咯血、颅内出血等严重不良反应发生。结论Anlotinib联合CAPTEM方案使SCLC脑转移患者在后线治疗中的疗效获益,同时具有较好的安全性。

Exploration of the Effect and Mechanism of Activating Blood Circulation and Stasis-Removing Therapy on Tumor Metastasis

Metastasis is one of the specificities of late stage tumor and also a lethal factor often encountered. The study of tumor metastasis has important meaning for prolonging patients＇ survival and elevating their quality of life, but no really ideal prevention and treatment method has been found so far. Recent researches showed that tumor metastasis is correlated with platelet aggregation and blood hyperviscosity manner. Therefore, the early application of surgery, radiotherapy, chemotherapy and biological therapies, in combination with Chinese medicine therapy for activating blood circulation and removing stasis （ABCRS） may be, after all, an effective approach. ABCRS therapy is an important therapy of Chinese medicine, which, composed of several methods like smoothening blood flow in vessels, promoting blood circulation and dispersing stagnant blood, could influence tumor metastasis to different extents, and could coordinate with some other Chinese medicine therapeutic methods like supplementing qi, promoting qi, clearing heat, removing toxic substances, warming meridian, dispelling wind, eliminating dampness, nourishing yin, dissolving sputum, relieving stagnancy, emptying viscerals, etc. The effect and acting mechanism of ABCRS on tumor metastasis is summarized in this paper and its bi-directional regulatory effects discussed as well.

MACC1与肿瘤的研究进展

恶性肿瘤的发生严重威胁着人类的健康及生存,对于其发病机制及转移机制仍然不是十分清楚。结肠癌转移关联基因1 (Metastasis-Associated in Colon Cancer 1,MACC1)是2009年发现的与结肠癌的发生密切相关的基因,不仅诱导肿瘤的发生、转移,且与肿瘤患者的预后及生存率明显相关,这主要与MACC1调节HGF/c-Met信号通路有关。在未来,MACC1有望成为肿瘤基因治疗的新靶点。本篇结合国内外的文献,就MACC1在肿瘤发生发展及转移过程的研究进展作一综述。

中药注射剂抗肿瘤治疗的医患偏好及共同决策比较分析

目的对中药注射剂抗肿瘤治疗的医患偏好及共同决策现状进行比较分析,为相关研究和临床实践提供参考。方法于2020年10月—12月对上海市9家三级医院的肿瘤治疗相关科室的185名医生及347名住院肺癌患者开展问卷调查,通过离散选择实验调查医患对中药注射剂抗肿瘤治疗方案的偏好属性,并采用条件Logit模型及混合Logit模型对医患的偏好属性进行分析,采用医患共同决策测量工具对决策行为进行现状描述与比较分析。结果医生更加关注恶心呕吐及其他毒副反应,患者更加关注疾病控制率及自付治疗费用。而在偏好差异的基础上,78.4%的医生以及90.2%的患者认为其参与的临床决策模式为共同决策模式。结论医患之间的偏好属性及决策模式存在差异,并会在一定程度上影响患者满意度及和谐医患关系。建议激发医生医疗服务积极性,促进医患共同决策。

基于“肺脑相系”理论探讨肺癌脑转移的中医发病机制

脑是肺癌最易发生转移的部位之一,探析肺癌脑转移的发病机制对肺癌远处转移的防治和预后具有重要意义。基于“肺脑相系”理论,结合肺、脑的生理和病理特点,从气机、五行、藏象、经络等角度阐述肺与脑的相关性,探讨肺癌脑转移的病机,进而为从肺论治肺癌脑转移提供理论依据。

结直肠癌根治术后复发转移相关因素的回顾性研究

目的探讨结直肠癌根治术后复发转移的影响因素。方法收集结直肠癌根治术后复发转移患者的相关资料,以出现复发转移为终点事件,用Kaplan-Meier法对结直肠癌根治术后患者进行生存分析,采用log-rank检验对临床因素[性别、年龄、术前血清癌胚抗原水平、手术方式、原发肿瘤位置、中医证型、化学疗法(以下简称“化疗”)完成情况、口服中药情况]及病理因素(大体形状类型、肿瘤直径、组织学类型、分化程度、脉管和神经侵犯、癌结节、吻合口瘘、淋巴结转移、淋巴转移率、浸润深度、TNM分期、所检淋巴结个数)进行单因素分析,采用Cox回归模型进行多因素分析。结果①共收集417例病例,结直肠癌根治术后复发转移的高峰时间为术后10~12个月,中位无复发生存时间(RFS)为15.3个月。②单因素分析结果显示,组织学类型、分化程度、浸润深度、淋巴结转移、TNM分期、淋巴转移率、脉管和神经侵犯、癌结节、吻合口瘘、中医证型、化疗完成情况、口服中药情况与结直肠癌根治术后RFS相关(P<0.05)。③多因素Cox回归分析结果显示,淋巴结转移[OR=1.724,95%CI(1.353,2.206)]、脉管和神经侵犯[OR=1.661,95%CI(1.116,2.465)]、癌结节[OR=1.801,95%CI(1.083,2.983)]、不同中医证型[OR=1.624,95%CI(1.126,2.473)]、完成全周期化疗[OR=1.738,95%CI(1.163,2.341)]、口服中药[OR=1.791,95%CI(1.328,2.264)]是影响结直肠癌术后RFS的独立危险因素,湿热内蕴证患者复发转移的风险较高,口服中药、完成全周期化疗可以延长患者的RFS。结论结直肠癌根治术后复发转移受淋巴结转移、脉管和神经侵犯、癌结节、化疗完成情况、中医证型、口服中药等因素影响,及早进行中医辨证论治有利于延长结直肠癌根治术后患者的生存期。

贾英杰运用“截断癌浊”法治疗恶性肿瘤经验探讨

贾英杰教授结合临床经验,提出“癌浊”病机理论,以“黜浊培本”为基本治则,并将姜春华教授截断疗法运用于恶性肿瘤的治疗。指出三焦功能失司是产生“癌浊”的重要环节,同时三焦也是“癌浊”传舍的通道,总结出“截断癌浊”的核心思想,即罢黜癌浊、截断来路为首要环节;疏利三焦,给邪出路为关键步骤;谨守病机,守方微调以达平和;倡立体疗法,多手段截断肿瘤转移。

The progress and perspective of nanoparticle-enabled tumor metastasis treatment

As one of the most serious threats to human being,cancer is hard to be treated when metastasis happens.What’s worse,there are few identified targets of metastasis for drug development.Therefore,it is important to develop strategies to prevent metastasis or treat existed metastasis.This review focuses on the procedure of metastasis,and first summarizes the targeting delivery strategies,including primary tumor targeting drug delivery,tumor metastasis targeting drug delivery and hijacking circulation cells.Then,as a promising treatment,the application of immunotherapy in tumor metastasis treatment is introduced,and strategies that stimulating immune response are reviewed,including chemotherapy,photothermal therapy,photodynamic therapy,ferroptosis,sonodynamic therapy,and nanovaccines.Finally,the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are discussed.

放化疗联合靶向免疫治疗复发转移性胰腺癌患者的预后分析

背景 早期胰腺癌可通过手术切除,辅以化疗、放疗等治疗方法,术后5年生存率约20%。局部-区域复发及远处转移是导致胰腺癌治疗失败的主要原因。目前关于复发转移性胰腺癌的治疗方案选择有限,且国内外相关文献报道较少。目的 探索胰腺癌根治术后复发转移患者接受放化疗联合靶向及免疫治疗的预后及其影响因素。方法 收集2011年1月-2021年9月在解放军总医院接受胰腺癌根治术后出现复发转移,而后行放疗、化疗、靶向和(或)免疫治疗等综合治疗的胰腺癌患者临床资料,分析预后因素及治疗失败模式。结果 41例接受综合治疗的患者纳入研究,男33例,女8例,中位年龄56岁。中位随访时间为75 (范围:31.5~118.5)个月,根治术后中位总生存期(median overall survival,m OS)为26.3个月,1年、2年、3年、5年的OS率为90.2%、63.4%、36.6%、19.5%;根治术后中位无病生存期(median disease free survival,mDFS)为9.8个月,1年、2年、3年、5年的DFS率为75.6%、19.5%、2.4%、2.4%。复发转移后的m OS为17.1个月,1年、2年、3年、5年的OS率为65.8%、44.0%、26.8%、4.8%。多因素Cox回归分析显示,对于根治术后总生存,男性(HR=6.98, P=0.011)患者预后更差,化疗周期数≥10 (HR=0.08,P=0.009)者预后较好;对于复发转移后总生存,男性(HR=3.85,P=0.024)、病理类型低分化者(HR=2.42,P=0.039)预后更差,术后化疗周期数≥10 (HR=0.16,P<0.001)者预后更好。肝转移(31.7%,13/41)和局部复发(46.3%,19/41)是根治术后主要的治疗失败模式。结论 放化疗联合靶向及免疫治疗在胰腺癌根治术后复发转移患者中具有较好的生存受益和耐受性,可作为复发转移患者的治疗选择。

节拍化疗联合内分泌治疗经标准治疗失败的转移性乳腺癌的临床疗效

目的:探讨节拍化疗联合内分泌治疗经标准治疗失败的激素受体阳性、人表皮生长因子受体2阴性的晚期乳腺癌的临床疗效。方法:回顾性分析汕头大学医学院附属肿瘤医院2014年7月—2021年8月收治的40例激素受体阳性、人表皮生长因子受体2阴性乳腺癌患者的临床资料,年龄41~79(55.8±8.3)岁。患者经标准方案治疗无效后,给予节拍化疗联合内分泌治疗。节拍化疗方案:依托泊苷胶囊,50 mg/d,连续口服20 d,28 d为1个治疗周期。对临床疗效及不良反应情况进行观察。结果:40例患者中无完全缓解,部分缓解3例(7.5%),病情稳定32例(80%),疾病进展5例(12.5%),临床获益率为77.5%(31/40),疾病控制率为87.5%(35/40)。中位无进展生存期为11个月(1~41个月)。绝经与否、分子分型、转移部位、治疗线数、既往化疗方案等因素与中位无进展生存期均无相关性(均P>0.05)。患者未出现不可耐受的不良反应。结论:节拍化疗联合内分泌治疗经标准治疗失败的激素受体阳性、人表皮生长因子受体2阴性的晚期乳腺癌可能是一种安全有效的治疗选择。

基于数据挖掘国医大师治疗胃肠道肿瘤用药规律探析

目的探讨国医大师治疗胃肠道肿瘤的用药经验。方法搜集120名国医大师治疗胃肠道肿瘤的医案,建立数据库,提取方药信息,应用频数分析、聚类分析和关联规则分析进行数据挖掘。结果共纳入77首方剂,涉及中药207种,总频次为1241次,高频次药物为甘草、白术、半夏、白花蛇舌草、黄芪等,用药分类以补虚药、清热药、理气药、化痰止咳平喘药和活血化瘀药为主,药性以寒、温、平为主,药味以苦、甘、辛为主,归经为脾、肝、胃经为主。关联规则分析得到“白术-甘草”“甘草-黄芪”等多种药物组合。聚类分析得到8组聚类组合和2组聚类方。结论国医大师治疗胃肠道肿瘤以益气健脾、疏肝理气、清热利湿、消食和胃、化痰散瘀为主要治则。

Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy

Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor therapy.However,its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment(ITM).Here,we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate(CaCO_(3))biomineralized Salmonella(Sal)as an in-situ cancer vaccine producer and systematical ITM regulator.CaCO_(3) can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading,and such biomineralization did not affect the bioactivities of the bacteria.Upon intratumoral accumulation,the CaCO_(3) shell was decomposed at an acidic microenvironment to atenuate tumor acidity,accompanied by the release of Sal and Ca^(2+)/A23187.Specifically,Sal served as a cancer vaccine producer by inducing cancer cells'immunogenic cell death(ICD)and promoting the gap junction formation between tumor cells and dendritic cells(DCs)to promote antigen presentation.Ca^(2+),on the other hand,was intermalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system,including DCs maturation,macrophages polarization,and T cells activation.As a result,such bio-vaccine achieved remarkable effcacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility.This work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.

Gene-guided OX40L anchoring to tumor cells for synergetic tumor“self-killing”immunotherapy

The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy.We developed a highly efficient delivery system HA/PEI-KT(HKT)to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide(CpG).On the one hand,CpG induced the expression of OX40 on T cells within tumors.On the other hand,OX40L plasmids achieved the OX40L anchoring on the tumor cell membrane to next promote T cells responses via OX40/OX40L axis.Such synergistic tumor“self-killing”strategy finally turned“cold”tumors to“hot”,to sensitize tumors to programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)blockade therapy,and promoted an immune-mediated tumor regression in both B16F10 and 4T1 tumor models,with prevention of tumor recurrence and metastasis.To avoid the side effects,the gene-guided OX40L anchoring and PD-L1 silencing was proposed to replace the existing antibody therapy,which showed negligible toxicity in vivo.Our work provided a new possibility for tumor“self-killing”immunotherapy to treated various solid tumors.