Hepatocellular carcinoma presenting with bone metastasis

Bone metastasis is an unusual complication of hepatocellular carcinoma. We report here 2 cases of patients with bone metastases of hepatocellular carcinoma at presentation. Patient No. 1 with liver cirrhosis and hepatocellular carcinoma was admitted with a bone metastasis in the rib. The patient was treated with hepatic arterial chemotherapy and rib resection. Patient No.2 was known to have an asymptomatic liver mass of uncertain histology for a year when he presented with back pain. Because of signs of spinal compression, laminectomy was performed, and the diagnosis of metastatic hepatocellular carcinoma was established. The presence of bone metastases in hepatocellular carcinoma at presentation is extremely rare. More frequently, bone lesions are observed after successful treatment of the primary liver tumor. Both surgery and radiotherapy are used as palliative treatment in bone metastases of hepatocellular carcinoma. The treatment of hepatocellular carcinoma presenting with bone metastasis by bone resection and intraarterial chemotherapy seems to be of limited impact on patient survival because of dissemination of micrometastases in other organs and the frequent presence of other comorbid conditions. However, effective palliation using this multimodality approach is feasible. Hepatocellular carcinoma should be considered in the differential diagnosis of bone metastases.     

Radiation therapy for bone metastasis of hepatocellular carcinoma

Background The efficacy of radiation therapy for bone metastasis of hepatocellular carcinoma was examined retrospectively. Methods The effect of radiation therapy for pain and paresis was evaluated in 38 patients who received planned radiation therapy with the total dose ranging from 26 to 60 Gy. The percentage regression of 14 metastatic bone lesions was calculated by using computed tomography: percentage regression=[(pre-radiation therapy tumor volume—postradiation therapy tumor volume)/pre-radiation therapy tumor volume]×100. Results The 1-, 2-, and 5-year survival rates of the 38 patients from the start of the radiation therapy were 30% 18%, and 9.0% respectively. The median survival period was 172 days. Pain relief was obtained in 91% of 44 painful bone metastases. No correlation was observed between the percentage regression and the tumor size. Complete regression of bone metastasis was noted in 6 of 14 patients who could be evaluated with computed tomography. Three of the 6 paiients with complete response have survived for more than 6 years after radiation therapy. Conclusion Radiation therapy is an effective method for palliation of bone metastasis. Although the prognosis of most patients with bone metastasis from hepatocellular carcinoma is poor, some attain longterm survival after treatment.     

Hepatocellular carcinoma presenting as bone metastasis

In a consecutive series of 395 patients with pathologically verified hepatocellular carcinoma, 20 patients (5%) had bone metastasis at initial presentation. Of these, 16 were men and four women ranging from 26 to 64 years of age (median, 50 years). The age, sex, hepatitis B surface antigen seropositivity, alpha-fetoprotein level, and frequency of associated cirrhosis were not statistically different from those in patients without initial bone metastasis. Initial presentation was usually the result of spinal lesion with neurologic compression, and chest wall or scalp mass. Metastasis most commonly involved spine and ribs, and occurred as osteolytic lesions or extrapleural mass. Computed tomography proved best for demonstrating an expansile soft tissue mass with bony destruction. Angiography showed hypervascular appearance over the destructive bone area. Treatment results were poor. The follow-up period ranged from 3 weeks to 14 months with a median survival of 5 months. The data suggested that hepatocellular carcinoma be ruled out in patients with osteolytic lesions.     

A possible role of VEGF in osteolytic bone metastasis of hepatocellular carcinoma

The incidence of bone metastasis was around 13% in 404 patients with hepatocellular carcinoma (HCC) who underwent treatment at the National Kyushu Cancer Center between 1988-97, which is a high value among various cancers. This is, in part, due to the prolonged survival time of HCC patients in recent years. Serum vascular endothelial growth factor (VEGF) levels were significantly elevated in HCC patients with bone metastases as compared to those in patients with liver cirrhosis/chronic hepatitis and HCC patients without bone metastasis. VEGF was positively stained in both the primary lesion and bone metastasis of HCC by immunohistochemistry. In the process of bone metastasis, an increase in bone resorption is a crucial step prior to invasion of the bone. VEGF, the most important angiogenic factor, has been shown to stimulate bone resorption through its effects on osteoclasts. Thus, HCC cells reach the bone marrow space, and then secrete VEGF which facilitates osteolytic bone metastasis. VEGF may also facilitate tumor growth in the bone by acting as an angiogenic factor once invasion of the bone is complete. This might be another reason for the high incidence of bone metastasis in HCC.     

355例恶性肿瘤骨转移的临床分析

目的 分析恶性肿瘤骨转移的临床特征,提高肿瘤骨转移的诊治水平.方法 对355例恶性肿瘤骨转移患者的发病特点、临床特征及生存期等进行回顾性分析.结果 恶性肿瘤骨转移男性多见,原发肿瘤以肺癌(44.5%)、乳腺癌(11.0%)多见.转移部位以胸椎(51.0%)、肋骨(43.1%)、腰椎(42.3%)、骨盆(26.8%)等多见.骨转移灶多发常见(83.4%).75.2%的患者表现为不同程度的疼痛,少数以局部肿块、功能障碍、病理性骨折甚至截瘫为主要临床表现,78例(22.0%)患者无症状.影像学表现以溶骨性破坏为主(82.2%).采用化疗、内分泌治疗、生物治疗、放疗、姑息性手术、双膦酸盐类药物及止痛等综合治疗.骨痛治疗临床获益率为98.5%,影像学有效率为72.2%.中位生存期为13.9个月,其中前列腺癌骨转移为34.9个月,肝癌骨转移为4.6个月.未合并其他部位或脏器转移者生存期长,中位生存期可达14.7个月,骨转移灶单发与多发者生存期无明显差异.结论 恶性肿瘤骨转移应争取早期诊断,其治疗应以提高患者生存质量、延长生存期为目标,以姑息治疗为主,采取综合治疗.     

Effects of alendronate on bone metastases and hypercalcemia after surgery for hepatocellular carcinoma

Alendronate, a bisphosphonate compound, lowers serum calcium in patients with cancer-associated hypercalcemia through its inhibitory effect on bone resorption and as a result symptoms associated with hypercalcemia improve. This study was carried out to investigate the effects of alendronate in patients with hypercalcemia due to bone metastasis of hepatocellular carcinoma (HCC). Two patients were evaluated. Their corrected serum calcium and alpha-fetoprotein (AFP) levels and their computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI) findings were evaluated before and during alendronate treatment. After treatment, not only the corrected serum calcium levels but also AFP levels and bone pain decreased; in addition, the regression of the metastatic focus was noted in the MRI analysis. These tumor inhibitory effects of alendronate have not been reported in HCC before; and alendronate might serve to prevent bone metastases in patients with HCC. In conclusion, two patients who developed hypercalcemia associated with bone metastasis after surgery for HCC were treated with alendronate and they experienced alleviation of the pain due to bone metastasis, improvement of their quality of life and a marked decrease in AFP levels with tumor regression.     

Hepatocellular carcinoma with a complete remission of bone metastasis achieved by arterial chemotherapy

Reported is the case of a hepatocellular carcinoma with a complete remission of the bone metastasis by arterial chemotherapy. The patient was 60 year old male, with the chief complaint being a tumor at the right side of the chest. The diagnosis was a hepatocellular carcinoma with a bone metastasis at the right 10th rib. The bone tumor showed no decrease in size after an intra-arterial injection of adriamycin, and radiation and or hyperthermia. Therefore, intra-arterial injections of mitomycin C mixed with lipiodol were instituted through the intercostal artery, and no bone tumor was noted after start of this therapy. Although the patient subsequently died, microscopic examination of a specimen obtained at autopsy revealed no malignant cells at the right 10th rib. Intra-arterial injections of anticancer agents mixed with lipiodol therefore are thought to be useful for the treatment of a bone metastasis.     

A case of hepatocellular carcinoma with bone metastasis responding to concurrent TS-1/low-dose cisplatin (CDDP) therapy and radiotherapy

A standard treatment for hepatocellular carcinoma with extrahepatic metastasis is not established and chemotherapy is ineffective. We experienced a case of hepatocellular carcinoma with bone metastasis that responded to concurrent TS-1/low-dose cisplatin (CDDP) therapy and radiotherapy. A 58-year-old male patient with left iliac bone metastasis after 2 hepatectomies was admitted to our hospital. The titer of serum AFP and PIVKA-II showed an extremely high levels, 12,350.5 ng/ml and 993 mAU/ml, respectively. The uptake area was found at the left iliac bone by scintigraphy with 99mTc-HMDP. Treatment with TS-1/low-dose CDDP therapy and radiotherapy (36 Gy) was started concurrently. The chemotherapy regimen comprised daily oral administration of 100 mg of TS-1 for 21 days and CDDP 10 mg/body infusion (day 1-5, 8-12). An additional 2 courses of TS-1/low-dose CDDP therapy were repeated. After that, severe pain diminished and the titer of serum showed AFP and PIVKA-II had improved to within normal ranges. The uptake at the left iliac bone was found to have decreased by scintigraphy. Adverse events were grade 1 nausea and leucopenia. TS-1/low-dose CDDP therapy seems to be applicable for the treatment of hepatocellular carcinoma with bone metastasis.     

An atypical extrahepatic metastasis of the distal phalanx from hepatocellular carcinoma

A 49-year-old woman presented with severe swelling and pain of the left little finger, which had exacerbated rapidly, in October 2006. The patient had a history of hepatocellular carcinoma and metastatic lung cancer. She had undergone partial hepatectomy for the hepatocellular carcinoma in September 2001 and pulmonary resection for metastatic lung cancer in November 2005. Roentgenogram of the hand on admission showed complete destruction of the distal phalanx of the left little finger. The final pathological result of the tissue obtained by disarticulation was an extrahepatic metastasis of hepatocellular carcinoma. Extrahepatic metastasis from primary hepatocellular carcinoma to the hand is very rare and only four cases have been reported in the literature. All the patients with extrahepatic metastases from the primary hepatocellular carcinoma to the hand had poor prognoses, but the patient presented in this article exhibited an unusual clinical course. The patient is still alive 1 year after the diagnosis of extrahepatic bone metastasis of the distal phalanx.     

应用MALDI-TOF-MS检测原发性肝癌骨转移患者血清的多肽差异谱

目的:应用基质辅助激光解析电离飞行时间质谱(matrix-assisted laser desorption ionization-time of flight mass spectrometry,MALDI-TOF-MS)系统分析原发性肝细胞癌(hepatocellular carcinoma,HCC)骨转移患者血清多肽差异谱,寻找具有潜在诊断意义的血清分子标志物.方法:收集50例HCC骨转移患者和50例HCC未骨转移患者的血清,分成训练组(76例)和验证组(24例).所有样本分别经ClinProt磁珠纯化、MALDI-TOF-MS检测及ClinProTools软件进行血清多肽差异谱分析.应用液相色谱质谱联用的方法对差异多肽进行序列鉴定.应用径向基神经网络(radial basis function neural network,RBFNN)算法建立诊断模型,并对诊断模型进行单盲法实验验证.结果:HCC骨转移患者中,共获得10条差异有统计学意义[P (Wilcoxon-test)＜0.001]的多肽峰,并成功鉴定了其中7条肽段(质荷比分别为1 780.7、1 866.5、2 131.6、2 880.4、1 532.4、2 489.8和2 234.3)的氨基酸序列,这些肽段的来源蛋白分别为甲胎蛋白(alpha-fetoprotein)、凝血酶原(prothrombin)、丝甘蛋白聚糖(serglycin)、交联-α-胰蛋白酶抑制物H4重链异构体2(isoform 2 of inter-alpha-trypsin inhibitor heavy chain H4)、自噬相关蛋白16-2异构体1(isoform 1 of autophagy-related protein 16-2)、转甲状腺素蛋白(transthyretin)和纤维蛋白β链(fibrinogen beta chain).选取2组间统计学差异最显著的6条多肽峰(质荷比分别为1 535.4、1 780.7、1 866.5、2 131.6、2 880.4和2 901.9)建立的诊断模型的识别率为89.47％,预测率为82.89％;单盲法验证模型的灵敏度为83％,特异度为92％.结论:筛选获得的差异血清多肽可能成为潜在的诊断HCC骨转移的分子标志物.     

Bone metastasis in hepatocellular carcinoma: need for reappraisal of treatment

Bone is an uncommon site of metastasis in patients with hepatocellular carcinoma (HCC), and often overlooked. We report two cases that had isolated bone metastasis; one of them had prolonged disease-free survival. The present series, along with the literature review, reinforces the idea that HCC should be considered in the differential diagnoses in patients presenting with metastases in bone. The presence of isolated bone metastases need not necessarily indicate poor prognosis, and all such patients need to be offered chemotherapy and at least one of the bone-directed therapies (either local radiation in cases of localized disease or bisphosphonates in the presence of extensive disease) as they may have a better outcome with therapy.     

A case of hepatocellular carcinoma with left thigh-bone metastasis

A 57-year-old man with hepatocellular carcinoma with left thigh-bone metastasis is reported. He was admitted to the hospital with left leg pain. A diagnosis of bone metastasis of unknown origin was based on X-ray films. Physical examination revealed hepatomegaly. Liver function tests showed a slight increase of alkaline phosphatase, GOT and GPT. In serological tests, the levels of alpha-fetoprotein and carcinoembryonic antigen were high. HBs antigen was negative. From the above data, hepatocellular carcinoma was diagnosed.     

Our experience of the treatment with sorafenib for unresectable hepatocellular carcinoma

We report here the experience of the treatment with sorafenib for advanced hepatocellular carcinoma (HCC) in our department. Forty patients received the therapy of sorafenib until April 2011. Twenty seven unresectable advanced HCC, 7 lung metastasis, 6 bone metastasis, 3 abdominal lymph node metastasis, and 2 peritoneal dissemination were included. The median duration of sorafenib treatment was 197 days. Grade 3 adverse event occurred in 9 patients (22.5%), and grade 4 adverse event occurred in 1 patient (3%). The response rate and disease control rate were 5% and 55%, respectively (CR 2, PR 0, SD 20, PD 9). The median overall survival was 15.2 months, and median recurrence-free survival was 3.7 months. These results suggested that a prevention of adverse events would lead to a continued treatment with sorafenib, and could expect to have a prolonged survival in patients with advanced HCC.     

Metastatic hepatocellular carcinoma presenting as facial nerve palsy and facial pain

Facial nerve palsy due to temporal bone metastasis of hepatocellular carcinoma (HCC) has rarely been reported. We experienced a rare case of temporal bone metastasis of HCC that initially presented as facial nerve palsy and was diagnosed by surgical biopsy. This patient also discovered for the first time that he had chronic hepatitis B and C infections due to this facial nerve palsy. Radiation therapy greatly relieved the facial pain and facial nerve palsy. This report suggests that hepatologists should consider metastatic HCC as a rare but possible cause of new-onset cranial neuropathy in patients with chronic viral hepatitis.     

肝动脉化疗栓塞联合索拉非尼治疗肝细胞癌合并肺转移的临床观察

目的 评价肝动脉化疗栓塞(TACE)联合索拉非尼治疗肝细胞癌(HCC)合并肺转移的疗效和安伞性.方法 30例伴有肺转移的晚期HCC患者,于TACE治疗后3周复查,如无禁忌证即开始服用索拉非尼,400 mg/次,2次/d;不能耐受时减至200 mg/次,2次/d.每4周进行疗效评估.结果 肺部转移病灶缩小6例,病灶稳定8例;肝脏病灶稳定22例,进展8例,在服药期问行TACE1～3次.不良反应包括手足皮肤反应7例,疲乏无力18例,脱发6例,腹泻6例,贫血和骨髓抑制5例,高血压2例,消化道出血1例.结论 HCC合并肺转移时,TACE联合索拉非尼治疗可有效控制疾病进展,安伞性及患者耐受性良好.     

肝动脉化疗栓塞联合索拉非尼治疗肝细胞癌合并肺转移的临床观察

目的 评价肝动脉化疗栓塞(TACE)联合索拉非尼治疗肝细胞癌(HCC)合并肺转移的疗效和安伞性.方法 30例伴有肺转移的晚期HCC患者,于TACE治疗后3周复查,如无禁忌证即开始服用索拉非尼,400 mg/次,2次/d;不能耐受时减至200 mg/次,2次/d.每4周进行疗效评估.结果 肺部转移病灶缩小6例,病灶稳定8例;肝脏病灶稳定22例,进展8例,在服药期问行TACE1～3次.不良反应包括手足皮肤反应7例,疲乏无力18例,脱发6例,腹泻6例,贫血和骨髓抑制5例,高血压2例,消化道出血1例.结论 HCC合并肺转移时,TACE联合索拉非尼治疗可有效控制疾病进展,安伞性及患者耐受性良好.     

恶性肿瘤患者血清骨钙素、甲状旁腺素含量与骨转移的相关性研究

目的：观察恶性肿瘤患者血清骨钙素（OC）、甲状旁腺素（PTH）的含量变化与骨转移发生、发展的关系。方法：放射免疫检测恶性肿瘤患者70例和正常健康人30例血清OC和PTH水平。结果：OC水平骨转移组高于正常对照组（P〈0．02），非骨转移组低于正常对照组（P〈0．01），骨转移组明显高于非骨转移组（P〈0．001），PTH水平骨转移组高于正常对照组（P〈0．01），非转移组与正常对照组比较无明显变化（P〉0．05），骨转移组明显高于非骨转移组（P〈0．01）。骨转移组转移病灶的数量与OC、PTH的含量成正相关。结论：血清OC、PTH对骨转移诊断具有一定临床价值。     

胃癌骨转移患者临床病理与预后分析

目的 本文旨在探讨胃癌骨转移患者的临床病理特征,筛选预后因子。方法 回顾性分析2007年4月—2013年12月哈尔滨医科大学附属肿瘤医院的157例胃癌骨转移患者临床资料。结果 157例胃癌骨转移患者中,确诊胃癌至骨转移的中位时间为280.5天。多发骨转移124例,单发骨转移22例。最常见的骨转移部位是脊柱(88.5%)、骨盆(51.6%)和肋骨(51.0%)。多数患者伴有骨外脏器转移(78.3%)。骨转移的胃癌患者病理分化大多较差,以低分化腺癌(69.3%)及印戒细胞癌及粘液腺癌(33.1%)多见。胃癌患者发生骨转移后的中位生存时间为109天。单因素分析显示CEA水平、LDH水平、血红蛋白浓度、白蛋白浓度、伴有骨外转移、化疗及双膦酸盐治疗与胃癌骨转移患者预后有关(P＜0.05)。多因素分析显示CEA水平、伴有骨外转移、化疗和双膦酸盐治疗均是胃癌骨转移预后的独立因素。结论 CEA升高及伴有骨外转移是其独立的不良预后因素,化疗和双膦酸盐药物治疗可能改善患者的预后。     

Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC

Brain metastases from hepatocellular carcinoma are extremely rare. The objectives of the current study were to assess the natural history, outcome, and possible prognostic factors in patients with brain metastases from hepatocellular carcinoma. Between 1995 and 2006, 6,919 patients with hepatocellular carcinoma were treated at Yonsei University Health System. Of those, 62 (0.9%) had a diagnosis of brain metastasis. We carried out a retrospective review of these 62 patients and performed a statistical analysis. The median age at the time patients were diagnosed with brain metastasis was 54 years. Forty-seven patients (76%) were male, and 53 patients had hepatitis B. Median time from diagnosis of hepatocellular carcinoma to brain metastasis was 18.2 months, and 5 patients had brain involvement as their initial presentation. Intracranial hemorrhage was frequently associated (54.8%) with brain metastasis. The most common presenting symptoms were motor weakness, mental change, and headache. Metastases were treated with whole-brain radiation therapy (WBRT) alone in 17 patients and gamma knife surgery alone in 10 patients. Six patients underwent surgical resection and 5 patients were treated with surgical resection followed by WBRT. Twenty-four patients (39%) received steroids only. Median survival after diagnosis of brain metastasis was 6.8 weeks (95% confidence interval: 3.8–9.8 weeks). Univariate analysis showed that treatment modality, number of brain lesions, α-fetoprotein, ECOG performance score, recursive partitioning analysis (RPA) class, and Child-Pugh classification had a statistically significant impact on survival. In multivariate analysis, treatment modality, number of brain lesions, and Child-Pugh classification were statistically significant prognostic factors for survival. The overall prognosis of patients with brain metastases from hepatocellular carcinoma is extremely poor. Nevertheless, some subsets of patients manifested the most favorable survival criteria (single brain metastasis and good liver function); thus, for at least these patients, treatment may result in an improved survival time.     

食管鳞癌患者远处转移部位与预后的相关性及生存分析

目的:探讨食管鳞癌患者远处转移部位与预后的相关性及生存分析。方法:从SEER数据库中提取2010年至2015年共439例食管鳞癌伴远处转移患者的临床资料，回顾性分析比较食管鳞癌远处转移部位与预后的相关性，通过χ2检验比较两组变量的差异，采用Kaplan-Meier法绘制生存曲线，Log-rank检验进行单因素分析，COX回归进行多因素分析。结果:肺转移、骨+肺转移、肝+肺转移患者预后较好；骨转移、脑转移、骨+脑转移、骨+脑+肝+肺转移患者预后较差。单因素分析显示:年龄、原发灶部位、T分期、手术情况、多器官转移情况与食管鳞癌远处转移患者的预后有关（P＜0.05）；多因素分析显示:年龄、手术情况与多器官转移情况是影响食管鳞癌远处转移患者总生存时间（OS）的独立危险因素。结论:食管鳞癌伴远处转移的患者整体预后较差，但年龄在60~69岁区间、接受手术治疗与较好的预后相关。仅单器官转移的食管鳞癌患者中，骨转移、脑转移患者预后较差；合并多器官转移的患者中，骨+脑转移、骨+脑+肝+肺转移患者预后较差。