Toll样受体4在人胰腺导管腺癌组织中的表达及其临床意义

目的：探讨人胰腺导管腺癌（pancreatic ductal adenocarcinoma,PDAC）组织中Toll样受体4（Toll-like receptor 4,TLR4）蛋白的表达及其临床意义.方法：收集2009年1月-12月在复旦大学附属中山医院行胰腺手术切除的6例非糖尿病（DM）的PDAC患者、6例PDAC合并DM患者的胰腺组织标本,采用免疫组化法检测TLR4蛋白在胰腺组织中的表达,并分析TLR4蛋白的表达与临床病理特征的关系.结果：非DM的PDAC患者的癌旁组织中TLR4蛋白的阳性表达率（15.8％）,与PDAC合并DM患者的癌旁组织中TLR4蛋白的阳性表达率（25.4％）,差异有统计学意义（P＜0.05）.PDAC患者癌组织中TLR4蛋白的表达较癌旁组织明显升高（67.6％比29.4％,P＜0.05）.TLR4蛋白阳性表达的PDAC患者其肿瘤最大径明显大于TLR4蛋白阴性表达的PDAC患者[（39.12±15.92）mm比（27.25±12.82）mm,P＜0.05].结论：TLR4蛋白高表达与DM及PDAC的发生、发展密切相关,且可能有促进肿瘤生长的作用.     

早期胰腺导管腺癌相关肿瘤标志物的筛选及临床意义

目的检索并分析可用于早期胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)诊断的肿瘤标志物。方法从癌症基因图谱计划(TCGA)数据库中检索出PDAC相关的17种候选肿瘤标志物;ELISA法对75例早期PDAC患者、25例中晚期PDAC患者、30例良性胰腺囊肿患者、30例慢性胰腺炎以及40例健康人对照血清标本中这17种候选肿瘤标志物进行检测,筛选出7种肿瘤标志物(IGFBP2、LRG1、CA19-9、REG3A、COL18A1、TIMP1和TNFRSF1A),并进一步筛选出在早期及中晚期PDAC患者血清中差异表达的3种肿瘤标志物(CA19-9、LRG1、TIMP1);采用ROC曲线和二元Logistic回归分析这3种肿瘤标志物对早期PDAC的诊断效能。结果 ELISA法检测结果表明,7种肿瘤标志物(IGFBP2、LRG1、CA19-9、REG3A、COL18A1、TIMP1和TNFRSF1A)在早期和中晚期PDAC患者血清中的含量均显著高于相关疾病对照及健康人对照组(P均0.05);进一步筛选结果证实,TIMP1、LRG1和CA19-9在早期、中晚期PDAC患者中的表达差异均有统计学意义(P均0.05);三者联合检测诊断早期PDAC的ROC曲线下面积(AUC~(ROC))为0.950,敏感性为91.4%,特异性为82.2%,准确性为91.3%,均显著高于单项检测及两两联合检测。结论 TIMP1、LRG1和CA19-9三者联合检测可显著提高早期PDAC的检出率,可用于早期PDAC的诊断。     

磁共振弹性成像评价胰腺导管腺癌病理分级及生存期

目的 探讨磁共振弹性成像(magnetic resonance elastography,MRE)弹性值评价胰腺导管腺癌(pancreatic adenocarcinoma,PDAC)肿瘤分级的价值,分析其对评估PDAC患者预后的价值.材料与方法 对62例诊断PDAC且接受胰十二指肠切除术患者行MRE检查,测量肿瘤弹性...     

肿瘤相关成纤维细胞与胰腺导管腺癌关系的研究进展

肿瘤相关成纤维细胞是胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)肿瘤微环境的重要组成部分,可通过分泌各种细胞因子影响PDAC的生物学行为,包括增殖、存活、侵袭、转移、血管生成和免疫抑制。本文就肿瘤相关成纤维细胞对PDAC细胞增殖、迁袭和免疫监视及与化疗药物耐药关系的研究进展作一综述。     

胰腺导管腺癌患者KRAS与SMAD4基因的突变情况

目的:研究胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)患者KRAS与SMAD4(也称DPC4)基因的突变情况,并探讨两者与PDAC患者临床病理特征的相关性。方法:收集50例未经放化疗的PDAC患者的肿瘤石蜡标本,通过Sanger测序法检测KRAS基因2号外显子与SMAD4基因全外显子的突变情况,并分析突变与临床病理特征之间的关系。结果:KRAS基因2号外显子突变率为72%(36/50),其中35例患者发生第12密码子错义突变(p.Gly12A sp 23例,p.Gly12Arg 2例,p.Gly12Val 8例,p.Gly12Cys 2例),1例患者同时发生第6密码子错义突变c.16C>T[p.(Leu6Phe)]和第23密码子同义突变(c.67C>T)。KRAS基因突变与肿瘤分期(P<0.01)、分化程度低(P<0.05)及淋巴结转移(P<0.01)相关。未检测出SMAD4外显子有突变。结论:KRAS基因与山东地区PDAC患者恶性程度高、预后差相关。SMAD4突变在本地区PDAC患者中较为罕见,提示SMAD4突变存在地区差异性。     

影像学检查在胰腺导管腺癌临床诊疗路径中的作用及价值

胰腺导管腺癌(pancreatic ductal carcinoma, PDAC)是一种极为凶险、高度恶性的消化道肿瘤, 其诊治路径中的常见问题主要包括:(1)筛查和早期检出; (2)术前评估及准确分期; (3)鉴别诊断; (4)随访及治疗评估, 影像学在其中均扮演重要角色。本文总结各种影像学检查在PDAC诊治路径中的作用及价值, 深入了解各种影像学检查的优势和局限性, 提供基于证据的PDAC影像学检查流程, 并重点阐述PDAC影像诊断与鉴别诊断要点, 从而更好地指导临床决策, 改善PDAC患者预后。     

三种方法治疗晚期非小细胞肺癌疗效对比

目的 探讨不同药物治疗晚期非小细胞肺癌的临床疗效.方法 回顾性分析吉非替尼、氯氧喹、泰素加卡铂分别治疗30例晚期非小细胞肺癌患者的临床疗效.结果 吉非替尼治疗晚期非小细胞肺癌患者效果明显.结论吉非替尼治疗晚期非小细胞肺癌有效率较高,不良反应发生率较低,是针对晚期非小细胞肺癌的良好药物.     

基于MALDI-TOF MS的血清多肽组学在胰腺良恶性疾病鉴别诊断中的应用

目的 探讨基于基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）的血清多肽组学在胰腺良恶性疾病鉴别诊断中的价值。方法 选取胰腺导管腺癌（PDAC）患者176例、慢性胰腺炎（CP）患者148例,按7∶3的比例随机分成训练集（PDAC 122例、CP 103例）和验证集（PDAC 54例、CP 45例）。采用弱阳性离子交换法结合磁珠吸附提取血清多肽,采用MALDI-TOF MS检测多肽谱。在训练集中采用二分类Logistic回归分析建立基于差异表达多肽的PDAC和CP的鉴别诊断模型,并在验证集中进行验证。采用纳米液相色谱-电喷雾串联质谱（nano-LC/ESI-MS/MS）测定差异表达多肽的氨基酸序列,并鉴定其所属的蛋白质。采用受试者工作特征（ROC）曲线评价鉴别诊断模型鉴别PDAC和CP的效能,并与血清糖类抗原19-9(CA19-9)的鉴别诊断效能进行比较。结果 共发现20个PDAC患者与CP患者之间有显著差异的多肽,依此建立的鉴别诊断模型鉴别PDAC和CP的曲线下面积（AUC）为0.988,最佳临界值为0.469,敏感性为94.26%,特异性为97.09%。在验证集中,该模型...     

紫杉醇联合顺铂治疗晚期卵巢癌患者的护理

目的 总结紫杉醇联合顺铂治疗晚期卵巢癌的护理.方法 对收治的62例晚期卵巢癌患者术后辅助紫杉醇与顺铂联合化疗,加强药物配制及输注过程中的护理,并针对并发症给予患者心理护理、对症护理,分析治疗及护理前后患者生活质量改善情况.结果 经治疗并行积极护理后,患者生活质量评分显著提高,与护理前比较差异显著.结论 合理、对症的护理措施可大幅缓解化疗不良反应,提高患者生存质量,对缓解晚期卵巢癌患者的病情具有重要意义.     

胃镜下微波烧灼联合局部化疗治疗晚期食管癌疗效观察

目的 观察比较胃镜下微波烧灼联合局部化疗治疗晚期食管癌和单纯胃镜下局部化疗治疗晚期食管癌的疗效.方法 86例晚期食管癌患者分成治疗组(44例)和对照组(42例),治疗组给予微波烧灼联合局部注射化疗药物治疗,对照组给予局部注射化疗药物治疗.治疗过程中观察患者近期疗效、生存期、转移情况、不良反应和并发症.结果 治疗组和对照组近期疗效食管梗阻缓解率分别为93.1%、59.5%;治疗组6、12、24个月生成率分别为97.7%、86.4%、65.9%.对照组6、12、24个月生成率分别为92.9%、40.5%、0.两组食管梗阻缓解率、24个月生成率差异有显著性.两组间转移病灶及不良反应差异无显著性.结论 胃镜下微波烧灼联合局部注射化疗药物治疗晚期食管癌,疗效较明显,可作为姑息治疗晚期食管癌的有效手段之一.     

Role of epithelial-mesenchymal transition in chemoresistance in pancreatic ductal adenocarcinoma

Pancreatic cancer (PC) is the seventh leading cause of cancer death worldwide. The vast majority of patients who have PC develop metastases, resulting in poor treatment effects. Although great progress in therapeutic approaches has been achieved in recent decades, extensive drug resistance still persists, representing a major hurdle to effective anticancer therapy for pancreatic ductal adenocarcinoma (PDAC). Therefore, there is an urgent need to better understand the drug resistance mechanisms and develop novel treatment strategies to improve patient outcomes. Numerous studies suggest that chemoresistance is closely related to epithelial-mesenchymal transition (EMT) of PDAC cells. Thus, this article summarizes the impact of EMT on PDAC from the perspective of chemotherapy resistance and discusses the possible novel applications of EMT inhibition to develop more effective drugs against PDAC.     

阿帕替尼联合化疗治疗晚期胃癌:1例报告并文献复习

胃癌是常见的消化道肿瘤之一，目前早期胃癌可以通过外科手术根治。但由于胃癌早期诊断率低，大部分患者就诊时已是局部晚期或发生转移，主要治疗方式仍然是化疗。然而单纯化疗的疗效仍十分有限且已达到瓶颈。随着肿瘤分子生物学及免疫学的发展，分子靶向治疗及免疫治疗成为晚期胃癌患者带来新的希望。本文报道阿帕替尼联合化疗治疗晚期胃癌1例，为晚期胃癌的靶向联合化疗提供参考。      

Long-term survival of a patient with pancreatic cancer and lung metastasis: A case report and review of literature

BACKGROUNDPancreatic cancer (PC) is a leading cause of cancer-related death, given its poor prognosis and the limited benefits of traditional therapies. As tumors become more genetically disorganized as they progress, genetic mutations might become new markers for us to predict their behavior. Nowadays, many inhibitors can selectively target gene products as a form of targeted therapy, with some showing promise as treatment for various types of cancer.CASE SUMMARYWe describe a rare case of a PC patient with long-term survival of more than 8 yr. The patient was diagnosed with pancreatic ductal adenocarcinoma (PDAC) with BAP1 and PIK3CA gene mutations and Raf1 fusion and achieved partial response twice after treatment with apatinib in combination with chemotherapy.CONCLUSION BAP1, PIK3CA mutations, and Raf1 fusion are rare in PDAC. Patients with these three gene alterations of PDAC may achieve long-term survival with apatinib. Further research in other contexts is needed to determine whether apatinib has ideal efficacy for PC treatment.     

Chemotherapy of advanced epithelial cancer - a critical review

This article is a short version of a report which presents a comprehensive analysis of clinical trials and publications examining the value of cytotoxic chemotherapy in the treatment of advanced epithelial cancer. As a result of the analysis and the comments received from hundreds of oncologists in reply to a request for information, the following facts can be noted. Apart from lung cancer, in particular small-cell lung cancer, there is no direct evidence that chemotherapy prolongs survival in patients with advanced carcinoma. Except for ovarian cancer, available indirect evidence rather supports the absence of a positive effect. In treatment of lung cancer and ovarian cancer, the therapeutical benefit is at best rather small, and a less aggressive treatment seems to be at least as effective as the usual one. It is possible that certain sub-groups of patients benefit from the treatment, yet so far the available results do not allow a sufficiently precise definition of these groups. Many oncologists take it for granted that response to therapy prolongs survival, an opinion which is based on a fallacy and which is not supported by clinical studies. To date, it is unclear whether the treated patients, as a whole, benefit from chemotherapy as to their quality of life. For most cancer sites, urgently required types of studies such as randomized de-escalations of dose or comparisons of immediate versus deferred chemotherapy are still lacking. With few exceptions, there is no good scientific basis for the application of chemotherapy in symptom-free patients with advanced epithelial malignancy.     

胆道系统肿瘤的药物治疗

手术切除是目前胆道系统肿瘤唯一的根治方法,但早期手术切除后复发率高,且患者诊断时大多为中晚期,已失去手术机会,预后较差。荟萃分析认为,术后辅助治疗能改善患者预后,BILCAP研究中卡培他滨辅助化疗虽未在意向治疗患者中达到研究终点,但在协定治疗患者中显示存在生存获益。吉西他滨联合顺铂(GC方案)仍是晚期一线标准化疗方案,吉西他滨联合替吉奥(GS方案)和吉西他滨、替吉奥联合顺铂(GCS方案)亦是一线治疗可选择的方案。IDH1、FGFR2作为肝内胆管癌的两种主要驱动基因已成为靶向治疗的研究热点,免疫检查点抑制剂单药或联合治疗研究亦逐步开展。本文旨在回顾胆道系统肿瘤的药物治疗进程,展望其治疗前景。     

Treatment for Hodgkin's disease

The mainstay of treatment for patients with localized stage HD was historically radiation therapy. However, chemotherapy has been substituting radiation therapy because of remarkable effects of chemotherapy and the late adverse effects of radiation therapy. In the treatment of advanced stage HD, ABVD therapy is currently identified as the best chemotherapy on the basis of equivalent efficacy and reduced toxicity comparing with MOPP therapy. The newer, intensified regimens such as escalated BEACOPP or Stanford V have demonstrated excellent disease control in preliminary results. For patients with primary refractory or relapsed HD after chemotherapy, current data support the use of high-dose chemotherapy with autologous stem cell rescue.     

光动力疗法联合化疗治疗中晚期食管癌患者的护理

目的总结光动力疗法联合化疗治疗中晚期食管癌的护理要点。方法对本院收治的33例中晚期食管癌患者实施光动力联合化疗,在治疗过程给予针对性的护理。观察患者疗效,并总结治疗护理要点。结果光动力疗法联合化疗治疗中晚期食管癌患者总有效率为90.9%,治疗过程5例患者发生丘疹红斑,6例发生胸骨后疼痛,1例发生急性左心衰,5例出现骨髓抑制,3例出现口腔炎等。结论光动力治疗联合化疗治疗中晚期食管癌,效果较好。护理方面要求治疗前应加强患者心理护理和疾病知识健康教育,以便增强患者治疗的信心;治疗过程既要考虑患者光动力治疗后出现的不良反应又要考虑化疗后出现的一系列并发症,其是晚期食管癌患者顺利治疗的保证。     

Principle and progress of radical treatment for locally advanced esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma is one of the most common malignant tumors in the digestive system in China and the world. Most patients are diagnosed as locally advanced or advanced stage. Concurrent chemoradiotherapy is the standard treatment for locally advanced esophageal squamous cell carcinoma. This study intends to summarize the evidence-based medical evidence of the treatment principle of locally advanced esophageal squamous cell carcinoma, the selection of radiotherapy dose, the outline of radiotherapy target and the selection of chemotherapy scheme. As a result, the effect of radiotherapy and chemotherapy is equivalent to that of surgery for the radical treatment of esophageal squamous cell carcinoma. In the era of immunization, it is recommended to use involved field irradiation. Fluorouracil plus cisplatin regimen is the standard chemotherapy regimen. FOLFOX regimen and paclitaxel plus fluorouracil regimen are optional concurrent chemotherapy regimens. The toxic and side effects of different chemotherapy regimens are different, which can be selected according to the actual situation of patients.     

Non-small cell lung cancer therapy in the elderly

To date, lung cancer is still the leading cause of cancer-related mortality worldwide, with the majority of lung cancers arising in the elderly. As a consequence, we can expect an increase in the number of older lung cancer patients considered suitable for chemotherapy in the near future. Elderly patients often have comorbid conditions and progressive physiologic reduction of organ function, which can make the selection of proper treatment daunting. Some patients will be able to tolerate chemotherapy as well as their younger counterparts, whereas others will experience severe toxicity and require treatment modifications. Thus, a major issue is effectively selecting patients suitable for standard or attenuated therapy. A comprehensive geriatric assessment performed at baseline is a useful tool that can help select the best treatment regimen to be administered to elderly patients. Until now, few trials have specifically focused on elderly patients affected by non-small cell lung cancer (NSCLC), particularly those with advanced disease; prospective elderly-specific studies in early stages are still lacking. High priority should be given to evaluating the role of new targeted therapies. Unfortunately, to date, clinical trials that include functional status and comorbidity as part of the geriatric assessment are rare. Future trials, specifically in the elderly population, should include these kinds of evaluations. The most recent therapies for the treatment of elderly patients with NSCLC will be discussed here.     

表皮生长因子受体突变与肿瘤标记物在晚期非小细胞肺癌靶向治疗中意义及相关性分析

目的 非小细胞肺癌(non-small cell lung cancer,NSCLC)约占肺癌总数的80％.本研究拟观察表皮生长因子受体(EGFR)基因突变和肿瘤标记物癌抗原125(CA125)与角蛋白19片段(CYFRA21-1)在表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗晚期NSCLC患者中的意义及其之间的相关性,探讨晚期NSCLC靶向治疗疗效评价指标及预后相关因子.方法 自2008年1月至2011年8月间,我院肿瘤内科收治的晚期NSCLC患者74例,依据方案分为化疗组和靶向治疗组.化疗组:以顺铂为基础的联合化疗(吉西他滨1000mg/m2第1,8天;多西他赛75mg/m2,第1天;长春瑞滨30mg/m2第1,8天+顺铂80mg/m2第1天),21天为1个周期;靶向治疗组:吉非替尼250mg/d,或者厄洛替尼150mg/d,餐后2小时口服.比较化疗组与靶向治疗组治疗前后CA125、CYFRA21-1变化.靶向治疗组依据是否接受基因检测分为突变组和未检测组,分别记录靶向治疗组中EGFR突变患者与未检测患者的临床疗效,同时统计两组接受靶向治疗后肿瘤标记物CA125、CYFRA21-1降低率,以及靶向治疗患者EGFR突变与临床疗效关系及与标记物的相关性.结果 靶向治疗后肿瘤标记物CA125与CYFRA21-1分别为(33.96±7.03)kU/L和(4.02±1.76)μg/L,与治疗前比较均明显降低(P＜0.05);化疗组治疗后肿瘤标记物CA125与CYFRA21-1分别为(36.24±6.03)kU/L和(3.80±1.35)μg/L,与治疗前比较也均明显降低(P＜0.05).EGFR突变患者疾病控制率为84.2％(16/19),明显高于EGFR突变未检测患者(P＜0.05);在EGFR突变患者经靶向治疗是肿瘤标记物CA125和CYFRA21-1降低率分别为89.5％(17/19)和47.4％(9/19),均明显高于EGFR突变未检测组,差异有统计学意义(P ＜0.05).结论 基因突变的晚期NSCLC患者EGFR-TKI靶向治疗临床疗效好;在EGFR-TKI靶向治疗过程中有一定比例的患者肿瘤标记物CA125和CYFRA21-1均有降低,且EGFR基因突变的患者接受靶向治疗后CA125、CYFRA21-1降低人数比率更高,CA125、CYFRA21-1变化可能与EGFR基因突变有关;CA125和CYFRA21-1可以作为潜在判定靶向治疗疗效的血清学指标,值得临床进一步研究.