GGT异常表达机制及定量HS-GGT诊断肝癌临床价值的研究

目的 :　探讨γ-谷氨酰转移酶 (GGT)在肝癌中的表达机制及其定量分析肝癌特异性 GGT(HS- GGT)的临床价值。方法 :从肝癌组织中纯化总 RNA,以 RT- PCR扩增 GGT基因并分析 M3位点甲基化状态 ,制备酶蛋白观察不同分子形式 GGT的表达与改变 ,并定量检测了不同肝病患者血清 HS- GGT水平。结果 :人肝癌至远癌组织中总 RNA浓度呈明显升高趋势 (P<0 .0 5 ) ,GGT基因检出率分别为 10 0 %、85 %和 75 % ,而 M3位点呈低甲基化状态 ,其频率分别为 75 %、5 5 %和 5 0 % ;癌组织中 GGT过度表达 ,血清 HS- GGT活性在肝癌组明显升高 ,以高于5 .5 U / L为界诊断肝癌的阳性率为 86 % ,而在其他患者中的阳性率低于 3%。结论 :基因甲基化状态降低导致 GGT异常表达 ,定量分析 HS- GGT有助于肝癌的诊断与鉴别。     

肝癌相关微小RNA的研究进展

微小RNA(miRNA)是一类具有转录后调节功能的非编码单链的小分子RNA,其在肿瘤形成过程中的作用已成为目前研究的热点.大量研究提示多种miRNA的异常表达参与了肝癌的发生发展,并可用于肝癌的诊断、治疗和预后评估.深入探讨miRNA与肝癌的关系及其分子机制将为肝癌的防治提供新的思路和方法.     

肝癌患者血清p16甲基化检测

肝细胞癌(hepatocellular carcinoma，HCC)是原发性肝癌的主要病理类型，其发病的分子机制尚不清楚。近年来发现，p16基因5’-启动子区CpG岛异常甲基化在许多肿瘤组织及患者血清或血浆循环核酸(ciI℃ulatingnucleicacid，CNA)中有较高检出率。我们用甲基化特异性PCR(methvlationspecific PCR，MSP)检测HCC患者血清p16基因启动子区CpG岛甲基化状态，分析p16甲基化与HBV感染、AFP等的关系，并探讨其临床意义。     

ALKBH1在肝癌中的预后价值和作用机制的生物信息学分析

背景与目的ALKBH1是重要的RNA 5-甲基胞嘧啶(m⁵C)、3-甲基胞嘧啶(m³C)和1-甲基腺嘌呤(m1A)去甲基化酶之一。目前,其在泛癌中的表达情况和预后价值尚未有系统性的研究。本研究旨在明确ALKBH1基因在泛癌中的表达情况及与患者预后的相关性,并探讨ALKBH1在肝癌发生、发展中的相关功能及可能机制。方法利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据分析ALKBH1在泛癌中的表达差异情况,并通过Kaplan-Meier和Cox回归法分析ALKBH1与各种肿瘤临床预后的相关性。聚焦ALKBH1在肝癌中的促癌机制,将TCGA肝癌队列分成ALKBH1表达高、低两组,对差异基因进行基因本体(Gene Ontology,GO)富集、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路分析、基因集变异分析(Gene Set Variation Analysis,GSVA)和肿瘤免疫细胞浸润评估(Tumor Immune Estimation Resource,TIMER)分析。最后使用cBioPortal、DNMIVD、StarBase数据库分析ALKBH1在肝癌中表达上调的原因。结果TCGA数据分析显示,ALKBH1在多种肿瘤组织中显著高表达,特别是肝癌。生存分析结果显示ALKBH1高表达与肝癌的预后不良相关(P<0.05)。基因富集与功能分析显示ALKBH1高表达肝癌组织的免疫反应和细胞周期相关通路显著富集,且免疫细胞浸润增加。ALKBH1在肝癌中表达上调与基因拷贝数变化和启动子甲基化无关,miR-122-5p和miR-33b-5p在肝癌组织中表达下调,且与ALKBH1表达负相关,可能是肝癌中ALKBH1表达上调的主要原因。结论受miR-122-5p和miR-33b-5p共同调控的ALKBH1可能参与肝癌的发生和发展,ALKBH1在肝癌组织中高表达可作为患者预后不良的分子标志物。ALKBH1可通过调控细胞周期和免疫细胞浸润促进肝癌发生和发展,有望成为肝癌的潜在治疗靶标。     

肝癌伴抑郁患者血清CRP、hs-CRP水平变化及其对预后的影响

目的 探讨抑郁对肝癌肝切除患者血清C反应蛋白(CRP)、超敏C反应蛋白(hs-CRP)水平及预后的影响。方法 纳入肝癌行肝切除术患者251例,术前3天使用医院焦虑抑郁量表-抑郁亚量表(Hospital anxiety and depression scale,HADS-D)、9条目患者健康问卷(9-item patients health questionnaire,PHQ9)对患者进行抑郁评估,根据评分结果将患者分为抑郁组(n=95)和无抑郁组(n=156),比较两组患者术前血清CRP、hs-CRP、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,生存分析Kaplan-Meier法比较两组患者术后无瘤生存期(DFS)和总生存期(OS)。结果 抑郁组患者的血清CRP、hs-CRP、ALT、AST水平均高于无抑郁组(P＜0.05)。随访3.5年结果显示,164例(抑郁组65例,无抑郁组99例)患者出现复发或转移、47例(抑郁组22例,无抑郁组25例)死亡,抑郁组患者DFS、OS均显著低于无抑郁组(P＜0.05)。多因素Cox回归分析显分析显示,肝功能分级、BCLC分期、抑郁是影响肝癌预后的独立危险因素。Spearman相关分析显示,患者抑郁程度与血清CRP、hs-CRP水平呈正相关(P＜0.05),DFS、OS与血清CRP、hs-CRP水平呈负相关(P＜0.05)。结论 抑郁可能介导血清CRP、hs-CRP水平升高,维持患者体内的炎症反应,导致肝功能损伤加重,ALT、AST水平升高,进而对肝癌患者预后造成不良影响。     

微小RNA-493-5p表达与肝癌患者临床特征及预后的关系

目的探讨微小RNA(miRNA)-493-5p表达情况与肝癌患者临床特征的关系及对患者预后的评估价值。方法选取78例肝癌患者作为肝癌组,并根据血清miRNA-493-5p表达水平的均值将肝癌组患者分为高表达组(n=36)和低表达组(n=42);另选取40例同期良性肝病患者作为良性组,25例健康体检者作为对照组。采用实时荧光定量逆转录-聚合酶链反应(qRT-PCR)测定血清miRNA-493-5p表达水平,比较肝癌组、良性组和对照组的血清miRNA-493-5p表达水平,分析血清miRNA-493-5p表达情况与肝癌患者临床特征的关系,比较不同血清miRNA-493-5p表达水平的肝癌组患者的生存情况,采用受试者工作特征(ROC)曲线分析血清miRNA-493-5p表达水平对肝癌患者预后的评估价值。结果肝癌组患者血清miRNA-493-5p的表达水平明显低于良性组和对照组(P﹤0.01)。血清miRNA-493-5p高表达组与低表达组患者的TNM分期、巴塞罗那临床肝癌(BCLC)分期比较,差异均有统计学意义(P﹤0.05)。截至随访结束,血清miRNA-493-5p高表达组患者的生存率高于低表达组患者(P﹤0.05)。ROC曲线分析结果显示,血清miRNA-493-5p表达水平对肝癌组患者预后评估的曲线下面积(AUC)为0.675(95%CI:0.554~0.796),灵敏度、特异度分别为56.76%、75.61%。结论肝癌患者血清中miRNA-493-5p的表达水平较低,且其表达水平与患者的临床分期有一定关系。miRNA-493-5p表达水平较低患者的生存率相对较低,术前血清miRNA-493-5p表达水平对肝癌患者的预后判断具有一定的评估价值。     

肝细胞癌VEGF、uPA和ICAM-1蛋白的表达及意义

转移和复发是肝癌患者术后主要的死亡原因 ,也是影响患者长期存活和治疗效果的主要障碍。我们通过检测血管内皮生长因子 (VEGF)、尿激酶型纤溶酶原激活物 (uPA)、细胞间黏附分子 1(ICAM 1)蛋白及增殖细胞核抗原 (PCNA)在肝癌中的表达 ,探讨与肝癌转移、复发有关的分子生物学机制。一、材料与方法1.组织标本 :12 3例选自同济医院病理科保存的肝外科中心 1998年 1月～ 1999年 12月肝癌患者手术标本。其中 ,临床无转移肝癌 (A组 ) 4 2例 ,肝内转移肝癌 (B组 ) 5 0例 ,伴门静脉主干癌栓肝癌 31例 (门静脉癌栓原发灶标本为C组 ,癌栓标本…     

血清甲胎蛋白联合癌胚抗原检测对肝癌的诊断价值

目的 探讨血清甲胎蛋白(AFP)联合癌胚抗原(CEA)检测对肝癌的诊断价值.方法 将160例肝癌患者作为观察组,再将同时期160例健康体检者作为对照组,检测两组患者的血清AFP、CEA水平和肝功能情况.比较不同肝功能、肿瘤直径和临床分期肝癌患者血清AFP、CEA水平,分析血清AFP联合CEA检查的诊断效能.结果 观察组患者AFP、CEA表达水平均明显高于对照组(P﹤0.01),观察组中肝功能异常患者AFP、CEA表达水平均明显高于肝功能正常患者(P﹤0.01).肿瘤直径≥5 cm患者血清AFP、CEA表达水平均明显高于肿瘤直径﹤5 cm患者(P﹤0.01).肿瘤分期为Ⅲ～Ⅳ期患者血清AFP、CEA表达水平均明显高于Ⅰ～Ⅱ期患者(P﹤0.01).受试者工作特征(ROC)曲线分析结果显示,血清AFP联合CEA检测的约登指数为0.850,灵敏度为90.00％,特异度为95.00％,曲线下面积(AUC)为0.939.结论 肝功能异常患者中AFP、CEA表达水平较高,其表达水平对临床诊断肝癌具有参考价值,两者联合检测肝癌具有较高的灵敏度和特异度.     

肝癌组织长链非编码RNA RP13-143G15.3表达临床意义分析

目的 近几年,大量的长链非编码RNA被发现,通过参与表观遗传、转录和翻译等实现对基因表达的调控,促进肿瘤细胞的发生发展和转移.探究长链非编码RNA RP13-143G15.3在肝癌及癌旁组织中的表达水平,分析其差异表达与临床指标之间的相关性,为肝癌的诊疗提供新的标志物.方法 对5例肝癌及癌旁组织进行长链非编码RNA(lncRNAs)表达谱筛查,选择具有表达差异的RP13-143G15.3扩大样本进行验证.收集2016-03-01-2016-06-30广西医科大学肿瘤医院肝胆外科进行肝癌切除术的56例患者肝癌及癌旁组织,采用实时荧光定量PCR技术检测RP13-143G15.3的相对表达水平,并分析其差异表达与患者临床特征、血清学指标及免疫组化指标的相关性.结果 5例肝癌组织中RP13-143G15.3表达高于癌旁组织,P=0.005.在大样本56例肝癌组织中相对表达量为0.026 5±0.006,癌旁组织中相对表达量为0.040 7±0.025,肝癌组织中RP13-143G15.3表达明显低于相应癌旁组织(Z=-3.842,P<0.001),与芯片筛查结果不一致.RP13-143G15.3的差异表达与患者乙肝携带史(χ2=4.667,P=0.031)、门脉高压(χ2=5.250,P=0.022)、甲胎蛋白水平(χ2=4.791,P=0.029)、乳酸脱氢酶(Z=-2.237,P=0.025)、谷氨酸脱氢酶(Z=-2.101,P=0.036)、纤维蛋白原(t=-2.103,P=0.040)、CA72-4(Z=-2.147,P=0.032)、免疫学指标CD34(χ2=9.516,P=0.023)及肿瘤增殖抗原(χ2=8.000,P=0.005)有关.结论 RP13-143G15.3在肝癌组织中表达下调,其可能起到抑癌作用,有望成为肝癌新的肿瘤标志物及分子靶点,为后续功能研究及机制研究提供理论基础.     

肝癌介入治疗患者的心理学特征及护理干预的疗效

目的分析肝癌介入治疗患者的心理学特征,探讨护理干预的疗效。方法选取2012年7月至2014年7月间收治的146例中晚期原发性肝癌行介入治疗患者,按随机数字表法分为观察组和对照组,每组73例。对照组患者给予常规护理,观察组患者在常规护理基础上加用护理干预。采用症状自评量表(SCL90)、焦虑自评量表(SAS)、抑郁自评量表(SDS)评定患者治疗前后的状况,对两组患者治疗后生活质量进行调查。结果两组患者治疗前后的心理状况均有明显改善,且观察组患者治疗后的抑郁、焦虑、敌对、恐怖、偏执评分明显低于对照组,差异有统计学意义(P<0.05)。观察组患者治疗后的身体功能、角色功能、情绪功能、认知功能、社会功能、总体生活质量方面的评分均显著高于对照组,差异有统计学意义(P<0.05)。观察组患者治疗后的SAS和SDS评分明显降于对照组,差异均有统计学意义(P<0.05)。结论护理干预可有效改善肝癌介入治疗患者的心理状态,提高患者的生活质量,值得临床推广应用。     

Real-world safety of nivolumab in patients with non-small-cell lung cancer in Japan: Postmarketing surveillance

Postmarketing surveillance of Japanese patients with unresectable, previously treated, advanced or recurrent non-small-cell lung cancer treated with nivolumab was undertaken during the conditional approval period. The study aim was to evaluate the occurrence of treatment-related adverse events of nivolumab in the real world. Patients were registered between December 2015 and March 2016 at 536 sites. Nivolumab was given intravenously (3 mg/kg every 2 weeks); the observation period was 12 months after the first dose of nivolumab. Patients were evaluated for safety (n = 3601; 18.2% ≥75 years, 22.4% ECOG performance status ≥2) and effectiveness (n = 3570). The frequencies of any grade and grade 3 or higher treatment-related adverse events were 47.1% and 15.9%, respectively. The most frequent treatment-related adverse events (any grade) were interstitial lung disease (6.4%), hypothyroidism (5.7%), and diarrhea (4.4%). Treatment-related adverse events of special interest (priority items) occurring at a frequency of 5% or more were adverse events related to interstitial lung disease, thyroid dysfunction, liver dysfunction, colitis/severe diarrhea, infusion reaction, and infusion reaction within 24 hours. Significant risk factors for these priority items were identified by competing risk analysis: interstitial lung disease (previous/comorbid interstitial lung disease, abnormal findings on chest imaging, and smoking history); liver dysfunction (previous/comorbid liver disease, smoking history, and metastasis); thyroid dysfunction (previous/comorbid thyroid disease and performance status); and colitis/severe diarrhea (treatment line 2 vs ≥3). The 12-month survival rate was 40.7%. In conclusion, the safety profile of nivolumab in this postmarketing surveillance was similar to that in clinical trials, and no new safety signals were identified. The study was registered with the Japan Pharmaceutical Information Center (clinicaltrials.jp: Japic-163271).     

Chronic comorbid conditions associated with risk of febrile neutropenia in breast cancer patients treated with chemotherapy

Chemotherapy-induced febrile neutropenia (FN) is associated with increased patient mortality and health care costs. Comorbid conditions such as liver and renal dysfunction have been linked to increased risk of FN. However, the effects of other chronic comorbid conditions on risk of FN have not been well studied. To examine the association between chronic comorbid conditions and FN in breast cancer patients, we identified incident breast cancer patients from 2000 to 2009 treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. Patients who received primary prophylactic granulocyte colony-stimulating factor (G-CSF) were excluded. We assessed history of comorbid conditions prior to cancer diagnosis using ICD-9 codes and disease registries. FN events were identified in the first chemotherapy cycle using a combination of ICD-9 codes and hospital discharge diagnoses. For each comorbid condition, propensity scores that included patient characteristics and other predisposing comorbid conditions were calculated and adjusted for in Cox models to determine associations between that comorbid condition and FN. We also evaluated secondary models that additionally adjusted for cancer stage, baseline absolute neutrophil count (ANC), chemotherapy regimen, and dose reductions. A total of 7,127 breast cancer patients were included; median age was 55 years, and the majority had localized (47 %) or regional (49 %) disease at diagnosis. In the first chemotherapy cycle, 335 (4.7 %) patients developed FN. Congestive heart failure (HR = 3.0; 95 % CI: 1.3–5.9), osteoarthritis (HR = 2.0; 95 % CI: 1.4–2.8), previous cancer (HR = 3.4; 95 % CI: 1.2–7.5), and thyroid disorder (HR = 1.6; 95 % CI: 1.1–2.3) were associated with increased risk of FN. These estimates were similar to those from secondary models that also adjusted for additional cancer and treatment-related covariates. Our findings suggest that several chronic comorbid conditions may be associated with risk of FN. This information, if confirmed by others, may aid clinical decision making with respect to use of prophylactic G-CSF during chemotherapy treatment.     

5-fluorouracil leucovorin and oxaliplatin (FOLFOX) in the treatment of metastatic colon cancer with severe liver dysfunction

Colon cancer patients with severe hepatic dysfunction secondary to liver metastases have limited treatment options. 5-Fluorouracil (5-FU) infusional therapy has been attempted, but data suggesting significant clinical benefit are lacking. Although both 5-FU and oxaliplatin have been well tolerated as single agents in patients with severe hepatic dysfunction, the combination of these drugs in this setting has not been investigated. We report on three patients with severe liver dysfunction secondary to metastatic colon cancer treated with a combination of 5-FU, oxaliplatin, and leucovorin (FOLFOX). All three patients tolerated chemotherapy well without any significant toxicity. Liver function tests improved within 2 weeks from the start of treatment. Clinical outcomes consisted of two partial responses and one disease stabilization. Two patients progressed after 4 and 7 months from FOLFOX initiation while treatment is ongoing in the third patient. FOLFOX chemotherapy is feasible and can be associated with positive outcomes in patients with metastatic colon cancer and severe hepatic dysfunction. This regimen should be investigated further in similar clinical settings.     

Management of pain in cancer patients with depression and cognitive deterioration

Patients with cancer are burdened with pain, ranging in prevalence from 14 to 100% in this population, and with comorbid behavioural symptoms such as depression and cognitive decline. However, the complex relationships between cancer pain, depression and cognitive decline, as well as their causes, still need to be clarified.Here, the existing literature on pain and its relationships with depression and cognitive decline in adult patients with cancer is reviewed, in order to understand the impact of pain on these interrelated symptoms, and the importance of its correct assessment and management.From the literature, it emerges that pain in cancer patients has a multidimensional phenomenology, which is the final product of a complex process involving emotional, cognitive, and sensory components. There is a substantial agreement that cancer patients with pain are at higher risk of having depression and cognitive decline. However, it is still controversial if these symptoms may fit into the same cluster, due to the paucity of studies exploring the simultaneous impact of pain on the psychological and cognitive well-being of patients with cancer, which would be consequential on their treatment and management. Finally, recent advances in immunology/oncology have provided novel insights into the pathophysiologic mechanisms supposedly underlying pain-related symptoms. Particularly, immune dysfunction may represent a common pathogenic ground of pain, depression and cognitive decline in cancer patients. In clinical practice, an appropriate assessment of pain should take into account the relationships with depression and cognitive decline, in order to develop more personalised and effective therapies for its management.     

Comorbid depression in surgical cancer patients associated with non-routine discharge and readmission

ObjectiveTo characterize the rates of depression across primary cancer sites, and determine the effects of comorbid depression among surgical cancer patients on established quality of care indicators, non-routine discharge and readmission.MethodsPatients undergoing surgical resection for cancer were selected from the Nationwide Readmissions Database (2010–2014). Multivariable analysis adjusted for patient and hospital level characteristics to ascertain the effect of depression on post-operative outcomes and 30-day readmission rates. Non-routine discharge encompasses discharge to skilled nursing, inpatient rehabilitation, and intermediate care facilities, as well as discharge home with home health services.ResultsAmong 851,606 surgically treated cancer patients, 8.1% had a comorbid diagnosis of depression at index admission (n = 69,174). Prevalence of depression was highest among patients with cancer of the brain (10.9%), female genital organs (10.9%), and lung (10.5%), and lowest among those with prostate cancer (4.9%). Depression prevalence among women (10.9%) was almost twice that of men (5.7%). Depression was associated with non-routine discharge after surgery (OR 1.20, CI:1.18–1.23, p < 0.0001*) and hospital readmission within 30 days (OR 1.12, CI:1.09–1.15, p < 0.001*).ConclusionRates of depression vary amongst surgically treated cancer patients by primary tumor site. Comorbid depression in these patients is associated with increased likelihood of non-routine discharge and readmission.     

Mechanisms of cancer-related fatigue

Cancer-related fatigue (CRF) is one of the most prevalent symptoms patients with cancer experience, both during and after treatment. CRF is pervasive and affects patients' quality of life considerably. It is important, therefore, to understand the underlying pathophysiology of CRF in order to develop useful strategies for prevention and treatment. At present, the etiology of CRF is poorly understood and the relative contributions of the neoplastic disease, various forms of cancer therapy, and comorbid conditions (e.g., anemia, cachexia, sleep disorders, depression) remain unclear. In any individual, the etiology of CRF probably involves the dysregulation of several physiological and biochemical systems. Mechanisms proposed as underlying CRF include 5-HT neurotransmitter dysregulation, vagal afferent activation, alterations in muscle and ATP metabolism, hypothalamic-pituitary-adrenal axis dysfunction, circadian rhythm disruption, and cytokine dysregulation. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is a characteristic, in particular chronic fatigue syndrome and exercise-induced fatigue. The mechanisms that lead to fatigue in these conditions provide a theoretical basis for future research into the complex etiology of this distressing and debilitating symptom. An understanding of relevant mechanisms may offer potential routes for its prevention and treatment in patients with cancer.Disclosure of potential conflicts of interest is found at the end of this article.     

The association of depression and anxiety with health‐related quality of life in cancer patients with depression and/or pain

Objectives: Depression is known to be a major problem in cancer patients, and evidence is emerging about the importance of anxiety. Because the disorders are highly comorbid, we examined the relationship of anxiety and depression with health‐related quality of life (HRQL) in cancer patients. Methods: Sample included 405 adult oncology patients participating in a randomized controlled trial of telecare management for pain and depression. This secondary cross‐sectional analysis of baseline data examined independent and additive effects of anxiety and depression on HRQL, disability, and somatic symptom severity. Results: In 397 patients who screened positive for either pain or depression or both, 135 had comorbid anxiety and depression, 174 had depression but not anxiety, and 88 had neither. Differences existed across all nonphysical HRQL domains and were more pronounced incrementally across the three groups in the expected direction. In GLM modeling, anxiety and depression were each associated with all the domains when modeled separately (p<0.0001). When modeled together, anxiety and depression had independent and additive effects on the mental health domains of HRQL and on somatic symptom burden. In other domains (vitality, perceived disability, overall quality of life, and general health perceptions), only depression had an effect. Conclusion: Anxiety and depression have strong and independent associations with mental health domains and somatic symptom burden in cancer patients. However, depression has a more pervasive association with multiple other domains of HRQL. Paying attention to both anxiety and depression may be particularly important when addressing mental health needs and somatic symptom distress. Copyright © 2009 John Wiley & Sons, Ltd.     

米氮平治疗大肠癌术后化疗相关焦虑抑郁的疗效观察

[目的]评价米氮平对大肠癌术后化疗患者焦虑、抑郁的疗效及化疗不良反应的影响.[方法]根据汉密尔顿焦虑—抑郁量表筛选出56例大肠癌术后化疗后出现焦虑、抑郁的患者,随机分为米氮平组和对照组,观察8周后评定米氮平对化疗患者焦虑、抑郁的疗效及对化疗不良反应的影响.[结果]米氮平组在化疗后第2、4及8周的焦虑、抑郁量表评分均低于化疗前水平(P＜0.05),且明显低于同期对照组(P＜0.01).米氮平组恶心呕吐、失眠等不良反应显著减轻(P＜0.05),且米氮平不加重骨髓抑制、肝肾功能损害及神经毒性等化疗不良反应(P＞0.05).[结论]米氮平干预大肠癌术后化疗伴发焦虑、抑郁障碍患者疗效显著,可有效改善生活质量,减轻化疗引起的不良反应.     

Effect of hepatic dysfunction due to liver metastases on the pharmacokinetics of capecitabine and its metabolites.

Capecitabine (Xeloda) is a rationally designed oral, tumor-selective fluoropyrimidine carbamate aimed at preferential conversion to 5-fluorouracil (5-FU) within the tumor. Because capecitabine is extensively metabolized by the liver, it is important to establish whether liver dysfunction altered the pharmacokinetics of capecitabine and its metabolites. This was investigated in 14 cancer patients with normal liver function and in 13 with mild to moderate disturbance of liver biochemistry due to liver metastases. They received a single oral dose of capecitabine (1255 mg capecitabine/m2) with serial blood and urine samples collected up to 72 h after administration. Concentrations of capecitabine and its metabolites were determined in plasma by high-performance liquid chromatography or liquid chromatography coupled to mass spectrometry and in urine by 19F-nuclear magnetic resonance spectroscopy. Although plasma concentrations of capecitabine, 5'-deoxy-5-fluorouridine, 5-FU, dihydro-5-FU, and alpha-fluoro-beta-alanine were, in general, higher in patients with liver dysfunction, the opposite was found for 5'-deoxy-5-fluorocytidine. These effects were not clinically significant. Total urinary recovery of capecitabine and its metabolites was 71% of the administered dose in patients with normal hepatic function and 77% in patients with hepatic impairment. The absolute bioavailability of 5'-deoxy-5-fluorouridine was estimated as 42% in patients with normal hepatic function and 62% in patients with impaired hepatic function. In summary, mild to moderate hepatic dysfunction had no clinically significant influence on the pharmacokinetic parameters of capecitabine and its metabolites. Although caution should be exercised when capecitabine is administered to patients with mildly to moderately impaired hepatic function, there is no need for, a priori, adjustment of the dose.