D-二聚体与乳腺癌的关系

作为凝血和纤维蛋白溶解活化的标志物，D-二聚体可快速评估血栓形成活性，并在静脉血栓栓塞症的诊断中发挥重要作用。研究表明在乳腺癌患者的血浆中D-二聚体浓度增加，因此，D-二聚体可以用作乳腺癌高凝状态的标志物。D-二聚体高表达反映了乳腺癌的恶性程度，与乳腺癌的侵袭转移密切相关，但与乳腺癌患者分子分型的关系有待研究。D-二聚体表达水平可以反映乳腺癌患者的身体机能状况，并可以指导构建静脉血栓栓塞症风险分层的风险评估模型。化疗和内分泌治疗会导致部分患者D-二聚体表达升高，在接受化疗前乳腺癌患者的D-二聚体浓度升高与化疗相对剂量强度降低相关。D-二聚体是指导乳腺癌患者抗凝治疗、判断预后的有效生物标志物。     

血清同型半胱氨酸及D-二聚体在消化系统肿瘤中的表达及临床价值

目的探讨血清同型半胱氨酸及D-二聚体在消化系统肿瘤中的表达及临床价值。方法选取消化系统肿瘤患者50例作为研究对象,并选取同期健康体检者30例作为对照组,检测两组血清同型半胱氨酸及D-二聚体的水平、检测不同消化系统肿瘤患者的血清同型半胱氨酸及D-二聚体水平、检测消化系统肿瘤患者不同病期和病情的血清同型半胱氨酸及D-二聚体水平,并计算消化系统肿瘤患者血清同型半胱氨酸及D-二聚体水平与DAI评分、CPB的相关性。结果研究组患者的血清同型半胱氨酸及D-二聚体水平显著高于对照组(P<0.05);研究组内不同肿瘤类型患者的血清同型半胱氨酸及D-二聚体水平无明显的统计学差异(P>0.05);研究组中,重度患者的血清同型半胱氨酸及D-二聚体水平最高,明显高于轻度患者和中度患者(P<0.05);研究组患者血清同型半胱氨酸及D-二聚体水平与DAI评分、CPB有明显的相关性,且为正相关。结论消化系统肿瘤患者血清同型半胱氨酸及D-二聚体水平可作为判断消化系统肿瘤病情严重程度的重要参考指标,具有极好的临床诊断价值。     

前列腺癌患者血浆D-二聚体水平及其临床意义

目的 探讨前列腺癌患者血浆D-二聚体水平,并分析其与临床病理特征及预后的关系。方法 采用酶联免疫吸附法检测147例确诊前列腺癌患者（前列腺癌组）的血浆D-二聚体水平,随访2年生存情况并分析其与临床病理参数（临床分期、盆腔淋巴结转移、远处脏器转移、前列腺特异抗原PSA水平和Gleason评分）及预后的关系。选取同期的92例良性前列腺疾病患者（良性疾病组）及70例男性健康体检者（健康体检组）作对照。结果 前列腺癌组D-二聚体水平为（0.52±0.04）mg／L,均高于良性疾病组的（0.26±0.08）mg／L和健康体检组的（0.19±0.07）mg／L（P＜0.05）;前列腺癌组不同临床分期、盆腔淋巴结转移、远处脏器转移、PSA水平、Gleason评分及预后的D 二聚体水平差异有统计学意义（P＜0.05）,且Ⅲ～Ⅳ期、有盆腔淋巴结转移、有远处脏器转移、PSA水平＞20ng／ml、Gleason评分≥8分和死亡的D-二聚体水平高于对应项（P＜0.05）。结论 前列腺癌患者的D-二聚体水平升高,且与转移、临床分期、PSA水平及Gleason评分有关,可能有助于评估前列腺癌患者的预后。     

D-二聚体与消化道恶性肿瘤

本文就D-二聚体在消化系统常见恶性肿瘤（胃癌、食管癌、大肠癌、原发性肝癌、胰腺癌）中的诊断、预后判断方面作用进行概述,并就D-二聚体升高对于消化道恶性肿瘤患者的早期诊断方面的作用,如早期治疗、提高患者预后等问题进行讨论。     

血浆D-二聚体在胰腺癌患者中的临床意义

【摘要】 目的 胰腺癌恶性程度极高,具有复发快、死亡率高,表现为预后差的临床特征。该研究以胰腺癌患者为对象,旨在探讨监测血浆D-二聚体水平在胰腺癌中的临床意义。方法 选取2012年10月至2018年11月在南京医科大学附属无锡市第二人民医院行胰腺癌根治术的患者,通过胶乳凝集法测定44例胰腺癌患者血浆D 二聚体水平,化学发光法测定患者血清糖类抗原19 9(CA19 9)水平,免疫组织化学法测定胰腺癌组织乙醛脱氢酶1a1(ALDH1a1)、人类表皮生长因子受体2(HER2)、P53的蛋白表达;通过Kaplan Meier法分析D-二聚体水平对胰腺癌患者无病生存期的影响。结果 胰腺癌患者术前D-二聚体异常高水平提示无病生存期短;复发期的D-二聚体水平显著高于初诊期;病程中,D-二聚体变化趋势与CA19 9具有一致性,且呈现术后降低复发时升高;D-二聚体高水平与ALDH1a1、HER2高表达相关。结论 胰腺癌患者D-二聚体水平具有监测复发、预测预后的价值。     

动态监测D-二聚体在肿瘤患者导管相关性血栓的临床意义

目的 探讨D-二聚体水平与肿瘤患者导管相关性血栓(Catheter related thrombosis,CRT)发生的相关性。方法 对100例住院的深静脉置管肿瘤患者进行前瞻性研究,动态监测血浆D-二聚体以及静脉多普勒超声检查,观察CRT的发生率、发生时间及血栓类型等。结果 CRT的发生率为12.6%,其中无症状血栓占83.3%。58.3%的血栓发生在置管后2周内,91.7%发生在置管后的置管后4周内。置管后2周血栓组D-二聚体水平显著高于非血栓组(P=0.013)。结论 肿瘤患者CRT大部分形成于深静脉置管后4周内,其中无症状性血栓的比例高,动态监测D-二聚体可能有助于其早期诊断。     

血浆D-二聚体在恶性淋巴瘤患者疗效评价中的价值

目的 探讨恶性淋巴瘤患者化疗前后血浆D-二聚体水平变化在疗效评价中的价值.方法 回顾性分析2011年1月至2013年11月天津医科大学肿瘤医院收治的经病理证实的恶性淋巴瘤患者402例,分析患者血浆D-二聚体水平与临床病理特征之间的相关性,评价患者化疗前后血浆D-二聚体水平变化与化疗效果的相关性.结果 恶性淋巴瘤患者的血浆D-二聚体水平中位数为734.51 ng/ml,明显高于正常范围（＜ 500 ng/ml）;高龄、非霍奇金淋巴瘤、乳酸脱氢酶升高、Ⅲ～Ⅳ期、B症状及国际预后指数（IPI）评分＞2分的患者,D-二聚体水平明显升高（均P＜ 0.05）.化疗有效组D-二聚体水平由化疗前的949.40 ng/ml降低至499.88 ng/ml,差异有统计学意义（P＜0.05）;化疗无效组D-二聚体水平由化疗前的611.09 ng/ml升高至899.76 ng/ml,差异有统计学意义（P＜0.05）.结论 恶性淋巴瘤患者血浆D-二聚体水平明显升高,且与临床病理特征相关,化疗前后血浆D-二聚体水平的变化可为疗效评价提供一定依据.     

血浆D-二聚体在肿瘤中的应用

D-二聚体是机体纤溶过程中产生的相关降解产物,能够反映机体的纤溶活性.研究显示,在肿瘤患者中,血液呈高凝状态,机体的血液状态直接反映患者病情,D-二聚体在评估肿瘤患者的病情、评价治疗效果及判断预后中有重要作用.     

非小细胞肺癌患者的基线D-二聚体水平与预后的关系

目的 探讨非小细胞肺癌(NSCLC)患者的D-二聚体水平与患者预后的关系.方法 回顾性分析经病理学或细胞学确诊的290例NSCLC的临床资料,分析患者D-二聚体水平与临床病理特征和预后的关系.结果 290例NSCLC患者中,D-二聚体正常(≤0.3μg/ml)和升高(＞0.3μg/ml)患者的中位总生存时间(OS)分别为54.0和46.2个月(P＜0.05).Ⅰ～Ⅱ期、ⅢA期、ⅢB期和Ⅳ期患者的中位OS分别为58.1、40.6、26.7和23.5个月(P＜0.05).在可手术患者(Ⅰ期、Ⅱ期和ⅢA期)中,D-二聚体水平正常和升高患者的中位无进展生存时间(PFS)分别为35.0和11.0个月(P＜0.05).淋巴结侵犯阴性和阳性患者的中位PFS分别为57.2和19.6个月(P＜0.05).在晚期NSCLC患者中,D-二聚体水平正常和升高患者的的中位OS分别是22.0和16.0个月(P＜0.05).Cox多因素分析结果显示,D-二聚体水平、TNM分期和美国东部肿瘤协作组(ECOG)评分为影响NSCLC患者OS的独立因素(均P＜0.05).D-二聚体水平和淋巴结转移为影响可手术NSCLC患者PFS的独立因素(均P＜0.05).D-二聚体和ECOG评分为影响晚期NSCLC患者OS的独立因素(均P＜0.05).结论 基线D-二聚体升高提示NSCLC患者临床分期晚、肿瘤体积大、淋巴结侵犯以及肿瘤组织血管生成丰富,能较好地预测不同分期患者的生存时间.     

D-二聚体水平与非霍奇金淋巴瘤患者预后关系的研究

  目的  本研究拟探讨D-二聚体升高与非霍奇金淋巴瘤（Non-Hodgkin Lymphoma NHL）患者总生存之间的关系。  方法  回顾性分析2000年1月至2009年12月天津医科大学附属肿瘤医院收治的经病理证实的NHL 425例,分析患者临床病理特征、D-二聚体及国际预后指数（the International prognostic index,IPI）对总生存的影响。  结果  血浆D-二聚体水平与IPI评分明显相关。低、中、高水平D-二聚体组5年生存率分别为97.4%,86.1%,35.0%（P < 0.05）。与IPI为0或1的患者相比,IPI≥4分者预后较差（P < 0.05）。Ann Arbor分期、病理类型、D-二聚体水平以及IPI评分是影响总生存的主要因素,多元分析表明IPI评分、血浆D-二聚体水平是独立预后因子。  结论  高水平的D-二聚体是NHL患者预后差的标志物。      

D -二聚体对晚期结直肠癌患者预后的影响

目的：探讨首次化疗前 D -二聚体水平对晚期结直肠癌患者预后的影响。方法：检测62例复发或转移性结直肠癌患者化疗前 D -二聚体水平,分析其与临床因素、化疗疗效、总生存期的相关性。结果：D -二聚体低水平组与高水平组在各临床因素间、化疗疗效间的比较均无统计学意义（P >0.05）,多因素生存分析显示 CEA 水平、D -二聚体水平是总生存期的独立预后因素（HR =3.454,95% CI =1.151~10.369, P =0.027;HR =2.380,95% CI =1.082~5.253,P =0.031）。结论：D -二聚体水平可作为晚期结直肠癌患者总生存期的预后因素,但不足以预测化疗疗效。     

Dose-finding and pharmacokinetic study of an all-oral combination regimen of oral vinorelbine and capecitabine for patients with metastatic breast cancer.

PURPOSE: A phase I study was performed to determine the maximal tolerated dose, recommended doses (RDs), safety and efficacy of oral vinorelbine when combined with capecitabine in an all-oral chemotherapy regimen in patients with metastatic breast cancer (MBC), with pharmacokinetic blood sampling to investigate potential drug-drug interactions. PATIENTS AND METHODS: Forty-four patients with MBC received as first- or second-line chemotherapy, oral vinorelbine at a dose of 60 or 80 mg/m2 on days 1 and 8 (and 15) with escalating doses of capecitabine from 1650 to 2500 mg/m2/day days 1-14 every 3 or 4 weeks. Three schedules were tested: day 1, day 8 and weekly regimens of oral vinorelbine with a 14-day course of capecitabine every 3 weeks; and a days 1 and 8 regimen of oral vinorelbine with a 14-day course of capecitabine every 4 weeks. RESULTS: With oral vinorelbine at 60 mg/m2, the RDs were established as oral vinorelbine 60 mg/m2 on days 1 and 8 plus capecitabine 2250 mg/m2/day days 1-14 and oral vinorelbine 60 mg/m2/week plus capecitabine 2000 mg/m2/day days 1-14. With oral vinorelbine at 80 mg/m2, the RD was oral vinorelbine 80 mg/m2 on days 1 and 8 plus capecitabine 2000 mg/m2/day days 1-14. Neutropenia was the main dose-limiting toxicity of the combination; it was reported in 40 patients (90.9%), with grade 3 in 14 patients (31.8%) and 6.2% of cycles, and grade 4 in 12 patients (27.3%) and 4.3% of cycles. Complications were rare with only three patients experiencing febrile neutropenia (one episode each). The most frequent non-haematological toxicity was gastrointestinal; however, the incidence of grade 3 was low, with no episode of grade 4. Hand-foot syndrome was reported in 14 patients (31.8%) and 22.6% of cycles, with grade 2 in two patients (4.5%) and 1.2% of cycles (two episodes each). No episode of grade 3 was observed. Objective responses were reported in 18 patients (three complete responses and 15 partial responses), yielding a response rate of 40.9% in the intention-to-treat population according to the investigator assessment. Results from the pharmacokinetic study demonstrated the absence of mutual pharmacokinetic interactions when both drugs were co-administered. CONCLUSIONS: The combination of oral vinorelbine and capecitabine is safe and easy to administer in an outpatient setting. This all-oral combination chemotherapy may offer a good alternative to the intravenous route for patients with MBC. Based on these promising results, a phase II study has started using oral vinorelbine 60 mg/m2/week with capecitabine 2000 mg/m2/day days 1-14 every 3 weeks as first-line chemotherapy in patients with MBC.     

Cyclin D1 overexpression associates with radiosensitivity in oral squamous cell carcinoma.

Overexpression of cyclin D1, a G1 cell cycle regulator, is often found in many different tumor types, including oral squamous cell carcinomas (SCC). Recent laboratory experiments have demonstrated that cyclin D1 levels can influence radiosensitivity in various cell lines. This study evaluated the relationship between cyclin D1 expression levels and radiosensitivity in nine oral SCC cell lines (HSC2, HSC3, HSC4, SCC15, SCC25, SCC66, SCC111, Ca9-22, and NAN2) and 41 clinical patients with oral SCC who underwent preoperative radiation therapy. Radiosensitivity of the nine oral SCC cell lines differed greatly in their response to radiation, assessed by a standard colony formation assay. Likewise, the expression of cyclin D1 varied, and the magnitude of the cyclin D1 expression correlated with increased tumor radiosensitivity. The similar significant association between the response to preoperative radiation therapy and cyclin D1 overexpression was observed in the oral SCC patients who were treated with preoperative radiation therapy. These results suggest that cyclin D1 expression levels correlate to radiosensitivity and could be used to predict the effectiveness of radiation therapy on oral SCC.     

Vinorelbine alternating oral and intravenous plus epirubicin in first-line therapy of metastatic breast cancer: results of a multicentre phase II study

The combination of intravenous (i.v.) vinorelbine and epirubicin is highly active in the treatment of metastatic breast cancer (MBC). In an effort to improve patient convenience, we investigated a regimen alternating i.v. and oral vinorelbine in combination with epirubicin as first-line chemotherapy of patients with MBC. In all, 49 patients with MBC received, as first-line treatment, a combination regimen consisting of i.v. vinorelbine 25 mg m(-2) plus epirubicin 90 mg m(-2) given on day 1, and oral vinorelbine 60 mg m(-2) on day 8 (or day 15 if neutrophils <1500 mm(-3)) every 3 weeks, in an open-label, multicentre phase II study. Treatment was to be repeated for a maximum of six cycles. The study population had a median age of 55 years, half of the patients had received prior adjuvant chemotherapy and 86% presented a visceral involvement. In all, 25 responses were documented and validated by an independent panel review, yielding response rates of 51% (95% CI: 36-66) in the 49 enrolled patients and 54.5% (95% CI: 39-70) in the 44 evaluable patients. Median durations of progression-free survival and survival were 8 and 20 months, respectively. Neutropenia was the main dose-limiting toxicity, but complications were uncommon, four patients having experienced febrile neutropenia and six having developed neutropenic infection. Other frequently reported adverse events included stomatitis, nausea and vomiting, which were rarely severe. No toxic death was reported. Among patients who received six cycles, global score of quality of life remained stable. This regimen alternating oral and i.v. vinorelbine in combination with epirubicin is effective and safe. Oral vinorelbine on day 8 offers greater convenience to the patient, and decreases the need for i.v. injection and reduces time spent in hospital. Therefore, oral vinorelbine is a convenient alternative to the i.v. form in combination regimens commonly used to treat MBC.     

血浆D-二聚体水平与转移性胃癌患者生存期的关系

Objective:The principal purpose of this study was to determine the relationship between level of plasma D-dimer and survival time in metastatic gastric cancer patients.Methods:We retrospectively collected the data of plasma D-dimer in metastatic gastric cancer patients admitted in our Department (Department of Oncology,The Affiliated Changzheng Hospital,The Second Military Medical University,Shanghai,China) from October 2006 to October 2008 and analyzed the relationship between level of plasma D-dimer and s...     

SPECT全身骨显像对多发性骨髓瘤和前列腺癌骨转移瘤的鉴别诊断价值

目的:探究多发性骨髓瘤和前列腺癌在单光子发射计算机断层成像术(SPECT)骨显像上的区别与联系.方法:对2013年6月至2015年12月收治的SPECT图像表现为全身广泛骨质代谢活跃灶的多发性骨髓瘤和前列腺癌患者进行回顾性研究,分析两者病灶部位、数目、形态以及各自典型影像表现.结果:25例多发性骨髓瘤患者共检出327个病灶,病灶最常累及部位分别为肋骨、脊柱、骨盆、颅骨、肩关节和股骨;33例前列腺癌患者共检出851个病灶,转移病灶最常累及部位分别为脊柱、肋骨、骨盆、股骨和肩关节、胸骨、颅骨、肱骨.多发性骨髓瘤在图像上表现为多发点状或类圆形浓聚,颅骨"帽状"浓集、肋骨"串珠样"浓集是其特征性表现;前列腺癌骨显像表现为放射性核素异常浓聚,大小、形态不一,多为点状、条状、片状或不规则浓集灶,全身骨骼"超级影像"为其特征性表现.结论:SPECT骨显像对多发性骨髓瘤和前列腺癌骨转移瘤有一定的鉴别诊断价值.     

脑转移癌特异性标志物表达及其意义

目的：探讨脑转移癌(BMC)特异性标志物表达，鉴别BMC原发来源。方法：对31例BMC进行临床病理观察；免疫组化EnVision法检测其TTF-1、TG、CK7、CK20等标志物表达。结果：31例中，男性19例，女性12例，男：女比例1．58：1；年龄32～82岁(平均61．7岁)；本组含转移性肺癌23例，其中TTF-1^ ／CK7^ 19例(82．6％)，TTF-1^-／CK7^ ／CK20^ 1例，单纯CK7^ 1例，TTF-1、CK7、CK20均阴性1例；转移性甲状腺癌2例，表达TTF-1^ ／TG^ ；转移性胃腺癌和食管腺癌各1例，CD7^ ／CD20^ ；转移性直肠腺癌1例，CK20^ ；转移性乳腺癌1例，CD7^ ；以上标记阴性并失访2例。术前原发癌未确诊率41．9％，经免疫标记、进一步检查后，未确诊仅为6．7％。结论：本组BMC以肺源性多见。TTF-1、TG、CK7、CK20等单克隆抗体配套免疫组化标记，将对BMC原发来源鉴别提供帮助。     

Oral paricalcitol (19-nor-1,25-dihydroxyvitamin D2) in women receiving chemotherapy for metastatic breast cancer: A feasibility trial

The vitamin D hormone, [1,25(OH)₂D, calcitriol], inhibits proliferation and angiogenesis in breast cancer but its therapeutic use is limited by hypercalcemia. Synthetic analogs of 1,25(OH)₂D that are less calcemic, such as paricalcitol (19-nor-1,25-Dihydroxyvitamin D₂), are used to treat hyperparathyroidism associated with chronic kidney disease. We sought to determine the safety and feasibility of taking oral paricalcitol with taxane-based chemotherapy in women with metastatic breast cancer (MBC). Oral paricalcitol was considered safe if it did not result in excessive toxicity, defined as grade 3 or higher serum calcium levels. It was considered feasible if the majority of women could take eight weeks of continuous therapy in the first three months. Serum calcium was monitored weekly and the paricalcitol dose was adjusted based on its calcemic effect. Intact parathyroid hormone (iPTH) was monitored as a marker of paricalcitol activity. Twenty-four women with MBC were enrolled. Twenty women (83%) received eight weeks of continuous therapy. Paricalcitol was well-tolerated with no instances of hypercalcemia grade 2 or greater. Fourteen women (54%) were able to escalate the dose. The dose range of paricalcitol in the first 3 mo was 2–7 ug/day. Serum iPTH levels at baseline were significantly higher in women with serum 25-Hydroxyvitamin D (25-OHD) levels less than 30 ng/ml (96.4 ± 40.9 pg/ml) vs. 46.2 ± 20.3 pg/ml (p = 0 0.001) (iPTH reference 12–72 pg/ml). We conclude that paricalcitol is safe and feasible in women with MBC who are receiving chemotherapy.     

The cost of systemic therapy for metastatic colorectal carcinoma in Slovenia: discrepancy analysis between cost and reimbursement

Background.

The aim of the study was to estimate the direct medical costs of metastatic colorectal cancer (mCRC) treated at the Institute of Oncology Ljubljana and to question the healthcare payment system in Slovenia.

Methods.

Using an internal patient database, the costs of mCRC patients were estimated in 2009 by examining (1) mCRC direct medical related costs, and (2) the cost difference between payment received by Slovenian health insurance and actual mCRC costs. Costs were analysed in the treatment phase of the disease by assessing the direct medical costs of hospital treatment with systemic therapy together with hospital treatment of side effects, without assessing radiotherapy or surgical treatment. Follow-up costs, indirect medical costs, and nonmedical costs were not included.

Results.

A total of 209 mCRC patients met all eligibility criteria. The direct medical costs of mCRC hospitalization with systemic therapy in Slovenia for 2009 were estimated as the cost of medications (cost of systemic therapy + cost of drugs for premedication) + labor cost (the cost of carrying out systemic treatment) + cost of lab tests + cost of imaging tests + KRAS testing cost + cost of hospital treatment due to side effects of mCRC treatment, and amounted to €3,914,697. The difference between the cost paid by health insurance and actual costs, estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009, was €1,900,757.80.

Conclusions.

The costs paid to the Institute of Oncology Ljubljana by health insurance for treating mCRC with systemic therapy do not match the actual cost of treatment. In fact, the difference between the payment and the actual cost estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009 was €1,900,757.80. The model Australian Refined Diagnosis Related Groups (AR-DRG) for cost assessment in oncology being currently used is probably one of the reasons for the discrepancy between pay-outs and actual costs. We propose new method for more precise cost assessment in oncology.