１５６０例非小细胞肺癌患者多因素预后分析

目的：综合治疗模式是提高非小细胞肺癌（ＮＳＣＬＣ）患者生存预后的主要手段,本研究结合临床资料对１５６０例大样本ＮＳＣＬＣ预后行多因素分析,建立具有临床实用价值的预后模型,为肺癌防治提供科学依据。方法：对１９９８年１月１日～２００４年１月１日期间我院收治的具有明确组织病理学诊断和临床分期的１５６０例ＮＳＣＬＣ患者资料,经病历查阅及严格随访,回顾性分析可能影响ＮＳＣＬＣ患者预后的相关因素。结果：共随访１５６０例ＮＳＣＬＣ患者,失随访７０例,有效病例１４９０例,失访率为４.５％。Ｃｏｘ单因素及多因素分析表明：ＴＮＭ分期、手术方式、化疗方案是否含铂类药物、ＫＰＳ评分是独立的影响ＮＳＣＬＣ患者预后的相关因素。该组病例１、３、５年生存率分别为６０.６％、４５.７％、２５.７％。结论：ＴＮＭ分期、手术方式、化疗方案是否含铂类药物、ＫＰＳ评分是影响ＮＳＣＬＣ患者的独立预后因素。     

非小细胞肺癌治疗现状及进展

非小细胞肺癌 (ＮＳＣＬＣ)约占全部肺癌的 80 % ,为肺癌中最常见的类型。ＮＳＣＬＣ有多种类型 ,其中以鳞型、腺型为主 ,其生物学行为、发展、分子生物学、药物敏感性、预后等相似之处较多 ,但仍存在各自特点[1] 。故在决定治疗方案时 ,就有着不同的要求。1　ＮＳＣＬＣ的临床生物学特点1.1　ＮＳＣＬＣ的恶性程度较低 ,局部发展慢 ,但存在微转移灶的可能 ,而这是治疗成败的焦点。ＮＳＣＬＣ的生长速度较小细胞肺癌 (ＳＣＬＣ)慢 ,其倍增时间 (ＴＤ)在鳞癌、腺癌中分别为 92天和 168天。然而倍增时间是根据Ｘ线中肺部原发灶计算的 ,而ＮＳ…     

非小细胞肺癌二线化疗现状

近年来 ,一些治疗非小细胞肺癌(ＮＳＣＬＣ)比较有效的新药不断问世。临床试验结果表明 :某些单药或联合用药治疗ＮＳＣＬＣ优于最好的支持治疗 (ＢＳＣ) ,使人们不再怀疑化学治疗在晚期ＮＳＣＬＣ治疗中的作用 ,化学治疗已成为晚期ＮＳＣＬＣ的常规治疗。然而晚期ＮＳＣＬＣ仍然是一个化疗相对耐药的肿瘤 ,单一化疗难以根治 ,实际上即使初始有效的患者终究也要复发。其中行为状态 (ＰＳ)评分较好、有条件接受再次化疗的晚期ＮＳＣＬＣ患者必然面对一个二线化疗的问题。本文拟就近年来ＮＳＣＬＣ二线化疗加以讨论。1　单药二线治疗晚期ＮＳ…     

水通道蛋白-１在非小细胞肺癌中的表达及其与临床病理特征的关系

目的　研究水通道蛋白-１（ＡＱＰ-１）在非小细胞肺癌（ＮＳＣＬＣ）组织中的表达水平及其与临床病理特征的关系。方法　用免疫组化法（Ｓ-Ｐ法）检测８０例ＮＳＣＬＣ组织中ＡＱＰ-１的表达水平,并分析其与分化程度、分期、细胞学类型和术后生存率之间的关系。结果　ＮＳＣＬＣ组织ＡＱＰ-１表达较正常支气管上皮组织和癌旁支气管上皮组织显著增强;肺癌Ｔ分期晚期、淋巴结有转移者ＡＱＰ-１的表达水平高,低分化肺癌ＡＱＰ-１表达水平高于高分化者;ＡＱＰ-１高表达肺癌患者术后长期生存率显著低于低表达者。结论　ＮＳＣＬＣ组织中ＡＱＰ-１表达异常增强,可能与肺癌的侵袭和转移有关,检测ＡＱＰ-１的表达水平可能在预测ＮＳＣＬＣ患者的预后中有一定临床意义。     

ＰＴＥＮ、ＰＩ３Ｋ、Ｓｕｒｖｉｖｉｎ在非小细胞肺癌中的表达及相关性

目的　检测ＰＴＥＮ、ＰＩ３Ｋ和Ｓｕｒｖｉｖｉｎ蛋白在非小细胞肺癌（ＮＳＣＬＣ）组织中的表达,并对其表达水平与ＮＳＣＬＣ临床特征之间的关系进行相关性分析,探讨其与ＮＳＣＬＣ的浸润、转移和预后的关系。方法　免疫组织化学ＳＰ法检测６０例ＮＳＣＬＣ组织、１９例正常肺组织中ＰＴＥＮ、ＰＩ３Ｋ和Ｓｕｒｉｖｉｎ蛋白的表达水平,运用单因素（Ｌｏｇ-ｒａｎｋ）和多因素（Ｃｏｘ比例风险模型）生存分析比较三者与各临床特征及预后之间的关系。结果　ＰＩ３Ｋ和Ｓｕｒｖｉｖｉｎ在ＮＳＣＬＣ中的阳性表达率显著高于正常肺组织（Ｐ＜０.０５）,ＰＴＥＮ在ＮＳＣＬＣ中的阳性表达率显著低于正常肺组织（Ｐ＜０.０５）;ＰＴＥＮ与ＰＩ３Ｋ、Ｓｕｒｖｉｖｉｎ蛋白表达呈负相关;ＰＴＥＮ阴性组的总生存时间显著低于阳性组,而Ｓｕｒｖｉｖｉｎ和ＰＩ３Ｋ阳性组的总生存时间低于阴性组（Ｐ＜０.０５）;临床ＴＮＭ分期、ＰＴＥＮ、ＰＩ３Ｋ及Ｓｕｒｖｉｖｉｎ表达是影响ＮＳＣＬＣ患者预后的独立因素。结论　ＰＩ３Ｋ和Ｓｕｒｖｉｖｉｎ在ＮＳＣＬＣ中的表达上调,ＰＴＥＮ在ＮＳＣＬＣ中表达下调,ＰＴＥＮ与ＰＩ３Ｋ、Ｓｕｒｖｉｖｉｎ蛋白表达呈负相关,三者均为ＮＳＣＬＣ预后的独立因素,监测它们的表达对评估ＮＳＣＬＣ患者的预后具有一定的价值。     

ＭＭＰ-７和ｕＰＡＲ在非小细胞肺癌的表达及其意义

目的：检测ＭＭＰ-１、ＭＭＰ-３、ＭＭＰ-７和尿激酶纤溶酶原激活物受体（ｕＰＡＲ）在非小细胞肺癌（ＮＳＣＬＣ）的表达水平,分析其表达水平与肺癌侵袭转移以及相关临床病理特征之间的关系。方法：免疫组织化学方法检测６６例ＮＳＣＬＣ和１０例正常肺组织中ＭＭＰ-１、ＭＭＰ-３、ＭＭＰ-７和ｕＰＡＲ的蛋白表达水平。结果：免疫组织化学检测显示ＮＳＣＬＣ组织ＭＭＰ-１和ＭＭＰ-３表达率较低,而ＭＭＰ-７和ｕＰＡＲ表达率较高,分别达到５５％和６１％,明显高于正常肺组织。ＭＭＰ-７的表达与ＮＳＣＬＣ淋巴结转移、分化程度以及预后密切相关;ｕＰＡＲ的表达与ＮＳＣＬＣ预后密切相关,与相关临床病理因素无关;ＭＭＰ-７和ｕＰＡＲ的表达呈正相关。结论：ＭＭＰ-７和ｕＰＡＲ的表达可作为ＮＳＣＬＣ患者预后评价的指标,可能成为抗肿瘤治疗的靶点。     

肺癌耐药研究进展

肺癌是最常发生的恶性肿瘤之一,已成为人类因肿瘤死亡的主要原因。尽管肺癌的治疗手段,包括手术、放疗、化疗,均有所改进,仍然只有约13%的患者能存活5年。小细胞肺癌(ＳＣＬＣ)对首次化疗非常敏感,有效率达90%,但大部分患者会复发,并形成耐药;对于非小细胞肺癌(ＮＳＣＬＣ...     

国产异长春花碱加顺铂治疗晚期非小细胞肺癌的临床研究

异长春花碱 (ＮＶＢ)是目前治疗非小细胞肺癌(ＮＳＣＬＣ)的有效药物之一 ,由ＮＶＢ加顺铂 (ＤＤＰ)组成的方案治疗ＮＳＣＬＣ有较好的疗效。我科自 2 0 0 0年 7月～ 2 0 0 1年 4月应用异长春花碱 (商品名盖诺 ,连云港豪森制药有限公司产品 )加ＤＤＰ治疗ＮＳＣＬＣ患者 39例 ,     

晚期非小细胞肺癌患者血清癌胚抗原变化与预后的关系

目的：探讨晚期非小细胞肺癌（ＮＳＣＬＣ）患者化疗前血清癌胚抗原（ＣＥＡ）基础水平和一线化疗２周期后血清ＣＥＡ的反应性与其预后的关系。方法：回顾分析１０６例晚期ＮＳＣＬＣ患者的临床病理特征和生存资料,采用放射免疫分析法检测患者化疗前及化疗２周期后血清ＣＥＡ的含量,并对检测结果进行统计分析。结果：血清基础ＣＥＡ水平与年龄及ＴＮＭ分期相关,ＣＥＡ的反应性与性别、年龄、病理类型、分期均无明显相关性。Ｋａｐｌａｎ-Ｍｅｉｅｒ生存分析和Ｃｏｘ模型多因素分析,血清基础ＣＥＡ水平、ＣＥＡ反应性与患者预后明显相关,且两者均是影响晚期ＮＳＣＬＣ患者预后的独立危险因素。亚组分析发现：腺癌组血清ＣＥＡ基础水平及ＣＥＡ反应性与预后存在明显相关性,而鳞癌组无明显相关性。结论：对于晚期ＮＳＣＬＣ患者尤其是腺癌患者,血清ＣＥＡ基础水平及化疗后血清ＣＥＡ的反应性可以作为判断ＮＳＣＬＣ预后的参考指标。     

非小细胞肺癌中P—gp,p53,bcl—2蛋白表达及其相关性研究

目的 研究非小细胞肺癌（ＮＳＣＬＣ）中ｐ５３、ｂｃｌ－２蛋白以及耐多药基因ＭＤＲ１产物Ｐ－糖蛋白（Ｐ－ｇｐ）的表达及相互关系,探讨它们在ＮＳＣＬＣ发展、预后及耐药中的作用。方法 采用免疫组化Ｓ－Ｐ法,对６０例ＮＳＣＬＣ及其癌旁正常肺组织中ｐ５３、ｂｃｌ－２蛋白和Ｐ－ｇｐ进行检测。结果 ｐ５３、ｂｃｌ－２蛋白及Ｐｇｐ在ＮＳＣＬＣ中表达明显高于癌旁正常组织（Ｐ〈０．０１）。两者都与患者预后显著负相关（     

Duration of hospitalization as a measure of cost on Children's Cancer Group acute lymphoblastic leukemia studies.

PURPOSE: We used duration of hospitalization as a surrogate for cost and event-free survival as a measure of effectiveness to estimate the cost-effectiveness ratios of various treatment regimens on Children's Cancer Group trials for acute lymphoblastic leukemia. PATIENTS AND METHODS: The analyses included 4,986 children (2 to 21 years of age) with newly diagnosed acute lymphoblastic leukemia enrolled onto risk-adjusted protocols between 1988 and 1995. Analyses were based on a model of 100 patients. The marginal cost-effectiveness ratio (hospital days per additional patient surviving event-free) was the difference in total duration of hospitalization divided by the difference in number of event-free survivors at 5 years for two regimens. Relapse-adjusted marginal cost of frontline therapy was the difference in total duration of hospitalization for frontline therapy plus relapse therapy divided by the difference in number of event-free survivors at 5 years on the frontline therapy for two regimens. RESULTS: One or two delayed intensification (DI) phases, augmented therapy, and dexamethasone all improved outcome. Marginal cost-effectiveness of these regimens compared with the control regimens was 133 days per patient for DI, 117 days per patient for double DI, and 41 days per patient for augmented therapy. Dexamethasone resulted in 17 fewer days per patient. Relapse-adjusted marginal costs were 68 days per patient for DI and 52 days for double DI. Augmented therapy and dexamethasone-based therapy resulted in 16 and 82 fewer hospital days, respectively. The estimated cost-effectiveness for treating any first relapse was 250 days per patient. CONCLUSION: DI, double DI, augmented therapy, and dexamethasone-based therapy are cost-effective strategies compared with current treatment of first relapse.     

Reversible alopecia universalis during treatment with PEG-interferon and ribavirin for chronic hepatitis C

The combination of PEG-interferon and ribavirin is currently recommended for the treatment of chronic hepatitis C, which is a common cause of morbidity and mortality worldwide. Hair disorders have often been described during interferon therapy, which include reversible hair discoloration, hypertricosis and alopecia. Ribavirin is reported to cause photoallergic reactions. We report two cases of alopecia universalis, with complete hair loss extended to the whole body, secondary to PEG-interferon and ribavirin combination therapy for chronic hepatitis C virus infection. Both female patients were infected by genotype 1 and presented alopecia during the second half of a 48-week therapy, concurrently with low levels of ferritin and thyroid dysfunction (patient 1) or depression (patient 2). Patient 1 withdrew from the therapy on week 26 and, due to the occurrence of maculo-erythematous cutaneous eczema, underwent corticosteroid therapy with complete hair regrowth. Patient 2 completed the scheduled therapy and showed a spontaneous complete hair regrowth. It should be noted that in spite of an early (within 4 weeks of therapy) virological response, patient 1 had a disease relapse after therapy withdrawal and corticosteroid therapy, while patient 2 maintained a sustained virological response. In conclusion, interferon therapy may trigger reversible alopecia universalis in susceptible patients. However, given the benign and reversible nature of this side effect, patients who achieve a virological response should be strongly advised to complete the treatment in order to prevent disease relapse.     

Thrombotic microangiopathy associated with interferon therapy for patients with chronic myelogenous leukemia: coincidence or true side effect?

BACKGROUND: Interferon-alpha (rIFN-alpha) is an established therapy for patients with myeloproliferative disorders. Unusual immune-mediated side effects have been associated with rIFN-alpha therapy. The association of rIFN-alpha therapy with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) has been reported infrequently. METHODS: Two patients with chronic myelogenous leukemia (CML) treated with rIFN-alpha-based regimens at the University of Texas M. D. Anderson Cancer Center developed thrombotic microangiopathy (HUS/TTP). The course of their disease is described. A third patient who developed renal failure while receiving rIFN-alpha therapy and had no other causative factor for his renal failure is also described. RESULTS: The patients were ages 24, 49, and 36 years, and they had received rIFN-alpha therapy for 37, 67, and 92 months, respectively, prior to the development of the disorder. One patient had discontinued rIFN-alpha 1 month before the event because of presumed rIFN-alpha-related cardiomyopathy. Two patients received hydroxyurea and cytarabine as part of their therapy. No patient was receiving any medication known to be associated with HUS/TTP. None had a history of diarrheal illness, but Escherichia coli OH157.H7 was grown from the stool of one patient. Two patients responded to plasmapheresis with normalization of counts and other indices, but both developed renal failure and became dependent on dialysis. One patient had evidence of disease progression and died of multiorgan failure. The third patient required dialysis for 18 months but is currently off dialysis; this patient has some residual renal impairment. CONCLUSIONS: Although no definitive association between rIFN-alpha therapy and thrombotic microangiopathies can be concluded from these data, these and other previously reported cases suggest that HUS/TTP is a rare side effect of rIFN-alpha therapy that should be managed in the standard fashion. Hypotheses regarding the mechanism underlying this association are discussed in this article.     

Breast-conserving therapy (BCT) for early-stage breast cancer

Several patient and tumor factors go into the decision process to determine whether a breast cancer patient is a good candidate for breast-conserving therapy. The patient must be seen by all disciplines before any therapeutic intervention. When used appropriately, breast-conserving therapy produces maximal disease control and improves quality of life in patients with early-stage breast cancer.     

Precision Surgical Therapy for Adenocarcinoma of the Esophagus and Esophagogastric Junction

IntroductionTo facilitate the initial clinical decision regarding whether to use esophagectomy alone or neoadjuvant therapy in surgical care for individual patients with adenocarcinoma of the esophagus and esophagogastric junction—information not available from randomized trials—a machine-learning analysis was performed using worldwide real-world data on patients undergoing different therapies for this rare adenocarcinoma.MethodsUsing random forest technology in a sequential analysis, we (1) identified eligibility for each of four therapies among 13,365 patients: esophagectomy alone (n = 6649), neoadjuvant therapy (n = 4706), esophagectomy and adjuvant therapy (n = 998), and neoadjuvant and adjuvant therapy (n = 1022); (2) performed survival analyses incorporating interactions of patient and cancer characteristics with therapy; (3) determined optimal therapy as that predicted to maximize lifetime within 10 years (restricted mean survival time; RMST) for each patient; and (4) compared lifetime gained from optimal versus actual therapies.ResultsActual therapy was optimal in 61% of those receiving esophagectomy alone; neoadjuvant therapy was optimal for 36% receiving neoadjuvant therapy. Many patients were predicted to benefit from postoperative adjuvant therapy. Total RMST for actual therapy received was 58,825 years. Had patients received optimal therapy, total RMST was predicted to be 62,982 years, a 7% gain.ConclusionsAverage treatment effect for adenocarcinoma of the esophagus yields only crude evidence-based therapy guidelines. However, patient response to therapy is widely variable, and survival after data-driven predicted optimal therapy often differs from actual therapy received. Therapy must address an individual patient’s cancer and clinical characteristics to provide precision surgical therapy for adenocarcinoma of the esophagus and esophagogastric junction.     

Clinical presentations and standard therapy of AIDS-associated Kaposi's sarcoma

The treatment plan for a patient with AIDS-related KS should be based on tumor characteristics, control of HIV infection, comorbidities, and patient treatment goals (see Table 1). Institution of optimal antiretroviral therapy is an essential component of KS therapy. When available, enrollment in a clinical trial should be considered, except for patients who are naive to chemotherapy with symptomatic or life-threatening KS. For a patient with minimal, indolent cutaneous disease, after optimal control of HIV replication, local treatment, investigational treatment, or interferon are reasonable considerations. For the patient with rapidly progressive, cutaneous disease, tumor-related symptoms, or visceral disease, cytotoxic chemotherapy in combination with antiretroviral therapy is the first consideration. Future advances undoubtedly will include pathogenesis-based agents, either alone or in combination with currently available cytotoxic therapy.     

非小细胞肺癌化疗的个体化

 个体化治疗是当前非小细胞肺癌的发展趋势, 但什么是个体化治疗,为什么要进行个体化治疗,哪些标志物可以用以指导个体化治疗以及如何在非小细胞肺癌中实施个体化治疗是我们面临的主要问题。本文对此逐一作一综述。     

晚期非小细胞肺癌维持治疗的新进展

 目前含铂两药化疗是晚期非小细胞肺癌（NSCLC）患者的一线治疗方案。然而,标准一线化疗方案的疗效已达到了一个平台,晚期NSCLC患者在一线治疗获得了客观缓解或疾病稳定后的维持治疗是目前研究的热点。培美曲塞成为晚期肺癌患者一线治疗达到缓解或稳定后的新的治疗手段,其耐受性好,提高了总体生存时间和无疾病进展时间,并且对于非鳞癌患者疗效显著。厄洛替尼（商品名：特罗凯）与一线化疗序贯治疗能显著延长患者无进展生存期,有研究表明标准治疗后的晚期NSCLC患者,无论病理类型、种族、性别、年龄、吸烟状态,应用厄洛替尼维持治疗均可临床获益且耐受性好。含铂两药一线化疗后使用吉非替尼（商品名：易瑞沙）维持治疗,可以给腺癌患者带来显著的临床获益。     

CD19及CD22嵌合抗原受体T细胞序贯治疗复发难治纵隔B淋巴母细胞淋巴瘤一例并文献复习

目的探讨CD19及CD22嵌合抗原受体T细胞(CAR-T)序贯治疗复发难治纵隔B淋巴母细胞淋巴瘤(B-LBL)的效果。方法报道华中科技大学同济医学院附属同济医院2017年3月收治的1例经CD19及CD22 CAR-T序贯治疗的复发难治纵隔B-LBL患者,分析CD19及CD22 CAR-T序贯治疗后1、3、6、12、18个月原发病缓解相关指标,并复习相关文献。结果该患者经过三线化疗后疾病复发进展,后行CD19及CD22CAR-T序贯治疗。在细胞免疫治疗过程中,患者出现1级细胞因子释放综合征,经积极治疗,病情稳定后出院。患者定期来院复查,动态追踪观察纵隔包块。行CAR-T治疗后患者纵隔包块明显缩小,病情持续缓解达18个月。结论 CD19及CD22 CAR-T序贯治疗为复发难治B-LBL提供了新的治疗手段。对于常规化疗效果欠佳的患者,应尽早积极行CAR-T治疗,从而提高缓解率,改善患者的远期预后。     

Treatment selection in metastatic renal cell carcinoma: expert consensus

In metastatic renal cell carcinoma (mRCC), many factors influence clinical decisions, including histology, tumour burden, prognostic factors, comorbidities, and the ability of the patient to tolerate treatment. Progression-free survival (PFS) durations reported from randomized trials of targeted therapies vary considerably, in part because of differences in patient characteristics. For first-line therapy, an estimate of PFS with sunitinib, bevacizumab plus interferon, or sorafenib in a 'general' population is 8-9 months, but each regimen is suitable for different patient categories. For example, sunitinib is suitable for all-prognosis groups, particularly younger, fitter patients; pazopanib for patients with a good or intermediate prognosis; bevacizumab plus interferon for good-prognosis patients or those with indolent disease; and sorafenib for patients at all prognostic risk levels, particularly the elderly and those with comorbidities. Sequential therapy with targeted agents provides significant benefit, and should be considered in all patients who can tolerate such treatment. Level 1 evidence supports sequential use of tyrosine kinase inhibitors, as well as these agents followed by everolimus. We consider how patient characteristics have influenced the results of studies of first-line therapy, and we provide expert opinion on the most appropriate treatment choices for particular patient groups receiving first-line and second-line therapy.