肝细胞肝癌骨转移的研究进展

肝细胞肝癌（HCC）是我国发病率较高的恶性肿瘤,骨骼是HCC常见的肝外转移部位。HCC骨转移不仅严重影响患者生命质量且缩短生存时间,但其发生机制尚未完全明确。文章从HCC骨转移的临床特征、发生机制、预后影响因素及诊疗进展等方面进行综述,以期为临床诊疗提供新思路。     

肝细胞肝癌骨转移在病理生理学及放射治疗中的研究进展

随着肝细胞肝癌(hepatocellular carcinoma,HCC)诊断技术及治疗方法的进步,近年来HCC患者的总生存期获得明显延长,因此HCC骨转移的发生率也有所提高。HCC骨转移大多数为溶骨性改变,血管形成、上皮-间质转化(epithelial mesenchymal transition,EMT)、转化生长因子-β(transforming growth factor-β,TGF-β)和破骨细胞在HCC骨转移的发生和发展中均有重要作用。而HCC骨转移预测模型的建立,将有利于对HCC骨转移进行早期干预,改善预后。局部放射治疗能显著缓解HCC骨转移的症状,尤其是骨痛症状。因此,本文就HCC骨转移在病理生理学方面的研究进展及放射治疗方面的研究进展作一综述,以期为HCC骨转移的治疗提供一些新的理论依据。     

线粒体DNA基因组不稳定性在肝细胞癌中的研究进展

肝细胞癌（hepatocellular carcinoma,HCC）发病率呈逐年上升趋势,但筛查和诊断方法仍有限。线粒体DNA（mitochondrial DNA,mtDNA）是真核细胞中重要的遗传物质,其基因组不稳定性（mitochondrial genome instability,mtGI）与癌症发生进展密切相关。mtGI主要包含单碱基替换、片段插入缺失、拷贝数变异等多种mtDNA变异形式。既往研究在HCC患者中发现大量mtDNA变异,因此探索mtDNA变异与HCC的关系有利于进一步阐明HCC发病机制,为HCC临床早期诊断及治疗提供更多可能性。本文将围绕mtDNA变异与HCC研究进展进行综述。     

305例非小细胞肺癌骨转移的诊断、治疗及预后分析

背景与目的骨转移是肺癌最常见转移部位之一，可引起疼痛、病理性骨折等，严重影响患者生活质量。本研究拟探讨骨扫描、MRI、CT、X线对非小细胞肺癌（NSCLC）骨转移的诊断价值，骨转移的治疗及预后相关因素分析。方法回顾分析16年我组连续诊治的561例晚期NSCLC的骨扫描检查，并与MRI、CT、X线检查骨转移方法对比。结果561例骨扫描中阳性455例，155例经临床排除骨转移，300例经临床、MRI／CT／X线证实或病理等证实为骨转移，假阴性5例，共305例骨转移。骨扫描总敏感性为98．36％，特异性为39．45％，准确度为71．48％。305例骨转移患者中有症状者138例，无症状者144例（47．21o．4），未记载者23例。多因素回归分析显示：转移在周围扁骨，骨磷治疗，无症状为有益的预后因素（P〈0．05）。结论骨扫描对于肺癌骨转移筛查具有肯定的临床价值。核素骨扫描可成为肺癌分期检查的筛查手段。骨扫描的不典型阳性病灶。可辅以CT或MRI检查。     

奥沙利铂治疗肝细胞癌耐药的相关机制研究进展

奥沙利铂在我国已被批准用于晚期肝细胞癌（HCC）的治疗,以奥沙利铂为基础的FOLFOX 4方案已成为晚期HCC的标准治疗之一,显著延长了患者的生存期,展现出安全有效、耐受性良好等特点。尽管如此,奥沙利铂治疗HCC的临床疗效仍十分有限,其治疗失败与HCC产生耐药密切相关。本文就奥沙利铂治疗HCC的耐药机制研究进展作一综述,希望能帮助临床和科研工作者了解最新动态,并为他们的工作拓宽思路。     

骨膦与化疗和放疗联合治疗肺癌骨转移的临床研究

本文依据５９例肺癌骨转移患者的临床资料，总结分析了肺癌骨转移的特点，着重探讨了骨膦与化疗和放疗联合治疗肺癌骨转移的疗效。结果示：骨膦治疗组３９例止痛总有效率为８７．２％，非骨膦治疗组２０例止痛总有效率为６０％，两者有显著差异（Ｐ〈０．０５）；骨膦治疗组的平均生存期（８．５个月）较非骨膦治疗组（５个月）明显延长（Ｐ〈０．０５）；骨膦治疗组较非骨膦治疗组无明显的毒性反应。另外骨膦用药的时间和疗程对疗效都有一定影响。     

晚期骨转移前列腺癌63例诊治分析

目的：总结晚期骨转移前列腺癌诊治经验。方法：63例前列腺癌骨转移患者行姑息性前列腺切除或内分泌治疗．其中1例辅助治疗后行根治手术。结果：52例（82．5％）随访6～72个月，平均30个月。15例治疗后12-48个月（平均21个月）转移死亡；1例因脑血管意外治疗6个月后死亡。生存36例中，随访至少1年（平均34个月），均无症状生存．内分泌治疗6个月PSA反应率达100％。结论：前列腺癌骨转移患者行内分；强治疗早期效果明确，对梗阻症状明显者加姑息性前列腺切除能提高生活质量。     

肝细胞癌免疫治疗的临床研究进展

早期肝细胞癌（hepatocellular carcinoma，HCC）手术切除、消融等局部治疗效果较好，但多数患者就诊时已属晚期，局部治疗效果有限，系统性治疗如索拉非尼（Sorafenib）等成为主要的治疗选择，但效果并不理想。免疫治疗近年获得了突破性进展，其疗效和安全性已在多种恶性肿瘤的临床实践中得到证实，有望改变现有的HCC治疗模式。本文就HCC免疫治疗的临床研究进展作一综述。     

绝经后乳腺癌骨转移患者骨相关事件及预后分析

目的探讨绝经后乳腺癌骨转移患者骨相关事件（SREs）、治疗及预后情况。 方法收集我院诊治的136例绝经后乳腺癌骨转移患者的资料,回顾性分析其临床病理特征,探讨骨相关事件、治疗及预后情况。结果患者平均年龄为58.5岁,≥60岁49例（老年组）,＜60岁87例（年轻组）。其中104例患者接受一线化疗,32例接受一线内分泌治疗。老年组较年轻组总SREs发生率有所增高,分别为449%和32.2%,但差异无统计学意义（P=0.194）。合并SREs的与不合并SREs的绝经后患者比较,总生存期（OS）显著缩短（P=0.011）。全组患者中位OS为48.0月,其中,老年组及年轻组中位OS分别为50.0月和40.0月,差异亦无统计学意义（P=0.689）。老年组中位无疾病进展时间（PFS）较年轻组延长,分别为17.0月和11.0月,但差异无统计学意义（P=0.161）。结论年龄是否大于60岁并没有明显影响绝经后乳腺癌骨转移的OS及PFS。绝经后乳腺癌骨转移患者,随年龄增加SREs发生率虽有增加,但差异无统计学意义;合并SREs的绝经后乳腺癌骨转移患者,总生存明显缩短。提示SREs可能增加死亡风险。     

Mcl-1在肝癌治疗耐药性中作用的研究进展

目前多数肝细胞癌（hepatocellular carcinoma,HCC）患者在进行药物治疗时容易出现显著的耐药性。明确肝癌耐药性的机理有助于提高药物治疗效果、降低治疗成本。髓细胞白血病因子-1（myeloid cell leukemia-1，Mcl-1）已被证实与HCC的药物耐药性密切相关。探究Mcl-1在HCC药物耐药性中的作用机制可深入解决HCC的难治性。本文从微小RNA、p53、细胞周期、化合物、传统中药等五个角度，就近十年来Mcl-1在HCC药物治疗耐药性中作用的研究进行综述，为HCC的治疗提供新的思路。     

Hepatocellular Carcinoma with Bone Metastases: Incidence,Prognostic Significance,and Management—Single-Center Experience

Background

Hepatocellular carcinoma (HCC) represents one of the most common causes of cancer-related deaths worldwide, with rising incidence in the USA. Bone metastases with HCC, in particular, have an extremely poor prognosis. We present prevalence, treatment, and survival of patients with bone and more specifically spinal metastases from HCC.

Methods

A retrospective analysis was done at a single tertiary care institution of patients with bone metastases from HCC between January 2005 and December 2015.

Results

Among 1017 patients with HCC, 20 were found to have bone metastases of which 11 had spinal metastases. Seventeen (85%) were male, with median age of 58 years at time of HCC diagnosis. Systemic chemotherapy and sorafenib were used in 12 (60%) patients, and 12 (60%) received radiation therapy. Among patients who did not receive therapy, median survival was 76 days. Median survival after diagnosis of metastasis in patients on sorafenib and radiation were 106 and 100 days, respectively.

Conclusion

Bone metastases in HCC are very rare and aggressive. Due to its rarity, optimal treatment strategies are not well defined. Early diagnosis is important for optimal therapy and improved survival.

     

脊柱转移瘤诊断与外科治疗的研究进展

脊柱转移瘤已成为日益严峻的临床问题。此类患者多属恶性肿瘤晚期,预期生存时间短,生活质量差,因此做到早诊断、早治疗就显得尤为重要。随着医疗技术和治疗理念的快速发展,脊柱转移瘤的诊断率已有提高,患者的生存时间和生存质量也有所改善。但具体治疗策略还是存在争议,这取决于多种因素。近年来不断有学者提出针对脊柱转移瘤的临床分型系统用以帮助制定治疗策略。随着外科技术的进步,手术治疗已成为脊柱转移瘤重要的治疗方式之一。本文将回顾国内外对脊柱转移瘤诊断和外科治疗策略的最新进展。     

Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments. Despite being widely used, alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC. The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins, metabolites, circulating tumor deoxyribonucleic acid, and circulating non-coding ribonucleic acid. Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment, thus prolonging survival outcomes. Currently, multiple clinical trials involving locoregional, systemic therapies, and combinations of these modalities are changing therapeutic strategies for different stage HCC. Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future. This review summarizes the most recent advances in non-invasive early molecular detection, current therapy strategies, and potential immunotherapeutic innovations of HCC.     

Clinical use of markers of bone turnover in metastatic bone disease

Bone metastases profoundly perturb normal bone remodeling. Biochemical markers of bone turnover have been shown to reflect these tumor-induced changes in bone remodeling and might therefore be useful in the diagnosis and follow-up of patients with malignant bone disease. Most markers of bone turnover, particularly those of bone resorption, are elevated in patients with established bone metastases. While this might indicate a role for bone markers as diagnostic tools in cancer patients, the available evidence does not provide any final conclusions as to the accuracy and validity of the markers presently used in the early diagnosis of bone metastases. Markers of bone resorption respond promptly and profoundly to bisphosphonate and antineoplastic therapy, and this response is associated with a favorable clinical outcome. Most markers, however, have been more useful in groups of patients monitored in clinical studies than in studies of individuals. While this makes them a good tool for drug development, it remains unknown whether the use of bone markers in a routine clinical setting has any defined beneficial effects on overall outcome in cancer patients. In particular, no study has addressed the question of whether patients with bone metastases should be treated according to their rate of bone turnover and what the treatment goals are in this respect. While it is unlikely that bone-turnover markers have sufficient diagnostic or prognostic value when used in isolation, the combination of these markers with other diagnostic techniques might be the way forward to improve the clinical assessment of patients with cancers of the bone.     

早期应用双磷酸盐对老年非小细胞肺癌骨转移的作用

目的:探讨早期静脉应用双磷酸盐对老年非小细胞肺癌骨转移的作用。方法:研究老年非小细胞肺癌患者68例。将骨密度T-Score≤-2.5作为双磷酸盐应用指征,在确诊骨转移之前即开始应用双磷酸盐定义为早期应用。按是否早期应用双磷酸盐,将68例患者按照临床分期分为两组,早期应用双磷酸盐者34例为治疗组,未早期应用者34例为对照组。比较两组骨转移发生率及确诊时间。结果:治疗组骨转移发生率47.06%(16/34),对照组82.35%(28/34),差异有统计学意义（P≤0.01)。治疗组中位骨转移发生时间较对照组延迟87天（218天 vs 131天）,差异有统计学意义（P=0.006）。结论:早期应用双磷酸盐治疗经选择的老年非小细胞肺癌患者,可以减少骨转移发生率,并推迟骨转移发生时间。     

Skull metastasis from hepatocellular carcinoma with chronic hepatitis B

A 56-year-old male visited our hospital for evaluation of an occipital mass. Contrast computed tomography showed hypervascular enhancement with osteolytic change in the skull and a huge enhanced mass in the liver. Magnetic resonance imaging showed bone metastasis in the thoracic vertebrae. Assays for hepatitis B surface antigen and hepatitis B core antibody were positive and his liver condition was Child-Pugh grade A. Our diagnosis was hepatocellular carcinoma (HCC) with skull and vertebrae metastases on chronic hepatitis B. He was treated with radiation therapy for bone metastases and transcatheter arterial chemoembolization for HCC. But he developed acute respiratory failure because of aspiration pneumonia, congestion and oedema with haemorrhage of the lungs and died. Dissection showed HCC with multiple bone metastases. The liver tumor was categorized as well-differentiated HCC, Edmondson classification I, trabecular type and pseudoglandular type. In the liver mild infiltration of lymphocytes was seen in Glisson's capsules which were significantly enlarged with well preserved limiting plates. Piecemeal necrosis was not obvious. No fibrosis was noted. An 8 cm × 7 cm × 3 cm metastatic lesion had formed in the left occipitotemporal part of the cranial bone. The lesion was osteolytic and showed invasion into the dura mater. Neither the subdural cavity nor the brain showed involvement from the metastatic tumor. However, skull metastasis from HCC is very rare and it affects the patient's prognosis and the quality of life. Therefore, it is very important to make an early diagnosis and carry out proper management of skull metastasis from HCC.     

Clinical features and prognostic factors in patients with bone metastases from hepatocellular carcinoma receiving external beam radiotherapy

BACKGROUND:

The current study was performed to identify clinical features and independent predictors of survival in patients with bone metastases from hepatocellular carcinoma (HCC).

METHODS:

Patients (n = 205) with bone metastases from HCC received external beam radiotherapy (EBRT) between 1997 and 2007. Demographic variables, laboratory values, tumor characteristics, and treatment modalities were determined before EBRT. The total radiation dose ranged from 32 to 66 grays (Gy) (median, 50 Gy) and was focused on the involved bone.

RESULTS:

In 80 of 205 (39.0%) patients with bone metastasis from HCC, tumors were characterized by osteolytic, expansile soft‐tissue masses. Overall pain relief from EBRT occurred in 204 patients (99.5%). No consistent dose‐response relation was found for palliation of bone metastases with doses between 32 and 66 Gy (P = .068), but the retreatment rate was higher in patients with expansile soft tissue. On univariate analysis, shorter survival was associated with poorer Karnofsky performance status (KPS), higher γ‐glutamyltransferase and α‐fetoprotein levels, tumor size >5 cm, uncontrolled intrahepatic tumors, multifocal bone lesions, involvement of spinal vertebrae, extraosseous metastases, and a shorter disease‐free interval after an initial diagnosis of HCC. On multivariate analysis, pretreatment‐unfavorable predictors were associated with lower KPS, higher tumor markers, and uncontrolled intrahepatic tumor when KPS was considered. The median survival was 7.4 months.

CONCLUSIONS:

The results of the current study provide detailed information regarding clinical features, survival outcomes, and prognostic factors for HCC with bone metastases in a relatively large cohort of patients treated with EBRT. These prognostic factors will help in determining which dose and fraction are appropriate. Cancer 2009. © 2009 American Cancer Society.     

Radiotherapy for bone metastases from hepatocellular carcinoma and pancreas cancer

There are few reports on the treatment for bone metastases from hepatocellular carcinoma (HCC) and pancreas cancer. We evaluated the therapeutic effects of radiotherapy (RT) in patients with bone metastases from these cancers. Bone metastases from HCC are typically lytic and expansive. We evaluated 13 patients with 16 bone metastases from HCC undergoing RT (30-40 Gy, median 39 Gy) in our department from September 2002 to December 2004. Tumor regression was evaluated by CT or MRI. More than 50% tumor regression was achieved in 4 of 16 lesions (25%). Pain relief was achieved in 12/13 (92%). The median survival was 7 months (95% confidence interval [CI], 4-10 months), and the 6-month and 12-month local control rates were 81% and 67%, respectively. For patients with a limited life expectancy, standard dose RT is appropriate, however,with more than one year life expectancy, investigation employing dose escalation or combination with surgery or TAE is needed. Thirteen patients with 18 bone metastases from pancreas cancer received RT (20-30 Gy, median 30 Gy) from September 2002 to March 2005. The median survival was 3 months (95% CI, 1-6 months). Pain relief was achieved in 12/13 (92%). The prognosis of patients with bone metastases from pancreas cancer is still very poor, and a single fraction or short fraction schedule RT is appropriate.     

Treatment of brain metastases from germ cell tumors

Brain metastases occur in approximately 10% of patients with advanced metastatic germ cell tumors. Patients with nonseminomatous histology, lung metastases, and high β-human chorionic gonadotropin levels are at higher risk for synchronous brain metastases at first diagnosis and for relapsing with brain metastases after successful cisplatin-based chemotherapy. Patients with brain metastases should undergo multimodal treatment strategies, including cisplatin-based combination chemotherapy plus radiotherapy or surgery. However, the optimal combination and sequence of these strategies remain unclear and may differ between subgroups. But in all cases, chemotherapy must be part of treatment, even in patients with isolated cerebral relapse without systemic disease.     

胃癌骨髓转移的血液学特征和治疗方式探讨

目的 探讨胃癌骨髓转移患者的临床病理特征、治疗及预后.方法 回顾性分析9例胃癌骨髓转移患者的临床资料,总结其临床特点、诊断和治疗方法.结果 9例患者的年龄为18~68岁,中位年龄为51岁,病理均为低分化腺癌.患者均伴有其他部位转移,常见淋巴结和骨转移.骨痛、非感染性发热、红细胞和血小板二系下降、碱性磷酸酶和(或)乳酸脱氢酶不同程度升高、外周血涂片可见幼稚细胞是胃癌骨髓转移的常见表现.胃癌骨髓转移患者的中位生存期为34 d(11~266 d).结论 胃癌骨髓转移患者的预后差,熟悉胃癌骨髓转移的临床特点有利于早期诊断.