Radiotherapy for painful bone metastases from hepatocellular carcinoma.

BACKGROUND: Painful bone metastases are one of the distressing clinical situations in patients with hepatocellular carcinoma (HCC). The purpose of the study was to evaluate the palliative effect of radiotherapy for painful bone metastases from HCC. PATIENTS AND METHODS: A retrospective analysis was performed upon 51 patients, who were treated with radiotherapy for painful bone metastases from HCC at 77 sites, from January 1991 to June 2000. Twenty patients (39%) presented synchronous metastases, and the remaining 31 patients (61%) showed metachronous metastases. In addition to bone pain, neurologic symptoms and a palpable mass were presented in 13 (25%) and seven (13%) patients, respectively. Twenty-one patients (41%) had a solitary metastasis and the most frequent site was the vertebra. The total dose of radiotherapy ranged from 12.5 to 50 Gy (median 30 Gy). RESULTS: On the Wisconsin Brief Pain Questionnaire, relief of pain was achieved at 56 sites (73%). The overall survival rate at 2 years was 4% and the median survival time was 5 months. Univariate analysis showed that tumor stage within the liver and the presence of metastases to organs, other than bones, were significant prognostic factors for survival (P < 0.05). CONCLUSION: In conclusion, radiotherapy provides effective palliation for patients with painful bone metastases from HCC during the substantial median survival time.     

Bone metastases from hepatocellular carcinoma:clinical features and prognostic factors

BACKGROUND: Bone metastases (BMs) from hepatocellu-lar carcinoma (HCC) is an increasingly common disease in Asia. We assessed the clinical features, prognostic factors, and differences in outcomes related to BMs among patients with different treatments for HCC. METHODS: Forty-three consecutive patients who were diag-nosed with BMs from HCC between January 2010 and Decem-ber 2014 were retrospectively enrolled. The clinical features were identified, the impacts of prognostic factors on survival were statistically analyzed, and clinical data were compared. RESULTS: The median patient age was 54 years; 38 patients were male and 5 female. The most common site for BMs was the trunk (69.3%). BMs with extension to the soft tissue were found in 14 patients (32.5%). Most (90.7%) of the lesions were mixed osteolytic and osteoblastic, and most (69.8%) patients presented with multiple BMs. The median survival after BMs diagnosis was 11 months. In multivariate analyses, survival after BM diagnosis was correlated with Karnofsky perfor-mance status (P=0.008) and the Child-Pugh classification (P<0.001); BM-free survival was correlated with progression beyond the University of California San Francisco criteria (P<0.001) and treatment of primary tumors (P<0.001). BMs with extension to soft tissue were less common in liver trans-plantation patients. During metastasis, the control of intrahe-patic tumors was improved in liver transplantation and hepa-tectomy patients, compared to conservatively treated patients. CONCLUSIONS: The independent prognostic factors of surviv-al after diagnosis of BMs were the Karnofsky performance status and Child-Pugh classification. HCC patients developed BMs may also benefit from liver transplantation or hepatectomy.     

大分割放疗联合唑来膦酸治疗肺癌骨转移的临床疗效观察

目的 观察大分割放疗联合唑来膦酸治疗肺癌骨转移的临床疗效及不良反应。方法 90例肺癌骨转移患者随机分成观察组（45例）和对照组（45例）。观察组静滴唑来膦酸4mg加局部大分割放疗30Gy／10f,之后再静滴唑来膦酸4mg×4～6次,1次／月;对照组则单纯放疗,方法剂量同上。结果 观察组止痛总有效率88．8％,显效率60％;对照组总有效率68．8％,显效率26．6％,两组比较P〈0．05。随访3个月后观察组与对照组止痛的总有效率分别为86．6％和57．5％（P〈0．05）。结论 大分割放疗联合唑来膦酸治疗肺癌骨转移,疗效确切,毒副反应轻,耐受性好。     

Skip lymph node metastases from a small hepatocellular carcinoma with difficulty in preoperative diagnosis

Recent autopsy studies have clarified the frequency of lymph node (LN) metastases from hepatocellular carcinoma (HCC). However, LN metastases commonly occur in advanced and poorly differentiated HCC and are very rare in small HCC. We encountered a patient with skip LN metastases from a small HCC, 10 mm in diameter. An intra-abdominal tumor adjoining the duodenum was detected by follow-up ultrasonography for viral hepatitis C. Computed tomography showed, in addition to the tumor bordering the duodenum, a small low-density area of the liver (S6), 2 cm in diameter, and a swelling of LN adjacent to the common hepatic artery. Upper gastrointestinal rentogenography revealed a compression of the duodenal second portion without irregularity of the mucosa. Our pre-operative diagnosis was duodenal gastrointestinal stromal tumor with LN metastasis and HCC or liver metastasis. However, laparotomy proved them to be LN metastases from a small HCC and partial hepatectomy and LN dissection were performed. The patient is doing well 22 months after surgery with no signs of recurrence. In the cases of HCC with LN metastases, the prognosis is generally very poor. However, in small HCC, the clinical characteristics are not fully evaluated. In treatment, we have to keep LN metastases, particularly skip LN metastases, in mind, even in cases of small HCC.     

Prognostic value of site-specific extra-hepatic disease in hepatocellular carcinoma: a SEER database analysis

Background: We the prognostic value of site-specific extra-hepatic disease in hepatocellular carcinoma (HCC) patients registered within the surveillance, epidemiology and end results (SEER) database.

Methods: SEER database (2010–2013) has been queried through SEER*Stat program to determine the prognosis of advanced HCC patients according to the site of extra-hepatic disease. Survival analysis has been conducted through Kaplan Meier analysis.

Results: A total of 4396 patients with stage IV HCC were identified in the period from 2010–2013 and they were included into this analysis. Patients with isolated regional lymph node involvement have better outcomes compared to patients with any other site of extra-hepatic disease (P < 0.0001 for both endpoints). Among patients with distant metastases, patients with bone metastases have better outcomes compared to patients with lung metastases (P < 0.0001 for both endpoints). Multivariate analysis revealed that younger age, normal alpha fetoprotein, single site of extra-hepatic disease, local treatment to the primary tumor and surgery to the metastatic disease were associated with better overall survival and liver cancer-specific survival.

Conclusion: Within the limits of the current SEER analysis, HCC patients with isolated lung metastases seem to have worse outcomes compared to patients with isolated bone or regional nodal metastases.?     

A 5-year survivor after resection of peritoneal metastases from pedunculated-type hepatocellular carcinoma

Received: January 9, 2001 / Accepted: May 11, 2001     

唑来膦酸联合放疗治疗恶性肿瘤骨转移疼痛

目的观察唑来膦酸联合放疗与单纯药物治疗恶性肿瘤骨转移癌性疼痛的疗效及不良反应。方法40例骨转移瘤患者随机分为A、B两组(各20例)。A组静滴唑来膦酸4 m g;B组静滴唑来膦酸4 m g后局部放疗。结果两组止痛效果比较:A组显效2例,有效12例,无效6例;B组分别为12、7、1例;两组比较,P<0.05。止痛起效时间:A组为(7.2±2.0)d;B组为(3.0±1.2)d;两组比较,P<0.05。两组均无严重不良反应。结论唑来膦酸联合放疗对恶性肿瘤骨转移所致的癌性疼痛具有良好的止痛效果。     

Zoledronic acid prevents bone loss after allogeneic haemopoietic stem cell transplantation

Allogeneic haemopoietic stem cell transplant (alloHSCT) patients are at increased risk of osteoporosis. Zoledronic acid (ZA) is a potent i.v. bisphosphonate; however, there are few data on ZA use after alloHSCT. The aim of this study is to examine the effect of a single 4 mg ZA infusion in alloHSCT patients with either osteoporosis (T-score < -2.5) or rapid bone loss post-alloHSCT. An uncontrolled, prospective study of 12 consecutive patients receiving ZA, predominantly within the first year post-HSCT. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the spine and proximal femur pretransplant, pre-ZA and post-ZA. The median annualized percentage change in total hip BMD between the pretransplant scan and the scan immediately before ZA was -13% (range, -51 to +3.6%). After ZA treatment, the total hip BMD increased by a median of +3.3% (range, -20.4 to +14.8%) in 75% of patients. The median annualized percentage change in femoral neck BMD between the pretransplant scan and the scan immediately before ZA was -13.2% (range, -40 to +1.0%). Post-ZA, femoral neck BMD increased by a median of +1.4% (range, -22.2 to +33.6%). Only one patient continued to lose bone from the femoral neck post-ZA infusion. The median annualized percentage change in spinal BMD pretransplant was -12.5% (range, -38 to +6.9%). Post-ZA, spinal BMD decreased by a median of -2.8% (range, -27.6 to +24.4%). Four patients continued to lose bone from the spine post-ZA. ZA reduces bone loss in most patients after alloHSCT. Our data require confirmation in a larger prospective, randomized study.     

Cutaneous metastasis from hepatocellular carcinoma as the first clinical sign

Hepatocellular carcinoma (HCC) is a tumor whose incidence has been increasing in recent years. The occurrence of cutaneous metastases from HCC, as the first sign of onset, is very unusual. We report a case of cutaneous metastasis from HCC appearing as a shoulder abscess and being the first clinical sign of the disease. We also examined the few published cases, and the diagnosis, treatment, and survival rate for this disease. Metastases of HCC should be included in the differential diagnosis of growing lesions in unusual localizations. Biopsies are required to confirm the diagnosis. The diagnosis of HCC from a cutaneous lesion is very uncommon and is associated with a poor prognosis.     

FDG positron emission tomography/computed tomography for the detection of extrahepatic metastases from hepatocellular carcinoma

Aims:  To compare the efficacy of positron emission tomography (PET) computed tomography (CT), multi-detector helical computed tomography (MDCT) and bone scintigraphy for the detection of extrahepatic metastases in patients with hepatocellular carcinoma (HCC).
Methods:  Thirty-four patients diagnosed with metastatic HCC were enrolled in this study. The lesions included lung ( n  = 18), bone ( n  = 12) and lymph node ( n  = 16) metastases. For receiver operating characteristic (ROC) analysis, lesions were diagnosed as metastatic HCC by two experienced abdominal radiologists. Another three physicians independently reviewed both positive and negative images. Each physician read three sets of images of MDCT, PET–CT and bone scintigraphy for bone metastasis.
Results:  The mean sensitivity and specificity for diagnosis of lung metastasis were 85.2 and 88.9% for MDCT, and 59.2 and 92.6% for PET–CT, respectively. For lymph node metastasis, these values were 62.5 and 79.2% for MDCT, and 66.7 and 91.7% for PET–CT, respectively; and for bone metastasis 41.6 and 94.5% for MDCT, 83.3 and 86.1% for PET–CT, and 52.7 and 83.3% for bone scintigraphy, respectively. The mean Az values were 0.95 and 0.77 for MDCT and PET–CT in lung metastasis, respectively, 0.75 and 0.80 for MDCT and PET–CT for lymph node metastasis, respectively, and 0.59, 0.88 and 0.62 for MDCT, PET–CT and bone scintigraphy for bone metastasis, respectively.
Conclusion:  PET–CT has high sensitivity and is more suitable for the detection of bone metastases from primary HCC, relative to MDCT and bone scintigraphy.     

Spinal cord compression secondary to bone metastases from hepatocellular carcinoma

Bone metastases are rare in primary hepatocellular carcinoma (HCC). Spinal cord compression (SCC) due to bone metastases occur commonly in patients with lung and breast carcinomas, and metastatic HCC is an unusual cause of SCC. Spinal cord compression is an oncologic emergency and treatment delays can lead to irreversible consequences. Thus, the awareness that SCC could be a potential complication of bone metastases due to HCC is of significance in initiation of early treatment that can improve the quality of life and survival of the patients, if diagnosed earlier. This paper describes four cases of primary HCC with varied manifestations of SCC due to bone metastases. The first patient presented primarily with the symptoms of bone pains corresponding to the bone metastases sites rather than symptoms of associated hepatic pathology and eventually developed SCC. The second patient, diagnosed as having HCC, developed extradural SCC leading to paraplegia during the course of illness, for which he underwent emergency laminectomy with posterior fixation. The third patient developed SCC soon after the primary diagnosis and had to undergo emergency laminectomy. Post laminectomy he had good neurological recovery. The Fourth patient presented primarily with radicular pains rather than frank paraplegia as the first manifestation of SCC.     

Prognostic analysis of pulmonary metastases from hepatocellular carcinoma

Purpose To analyze the prognostic factors for the patients with lung metastases from hepatocellular carcinoma (HCC). Methods and materials One hundred and five patients with lung metastases from HCC were analyzed retrospectively. We analyzed the impact factors, including the gender, age, liver function, serum AFP and γ-GT level, the status of intrahepatic tumor and pulmonary metastases and treatment for them, the distant metastases beyond the lung, as well as the causes of death. The overall cumulative probability of survival was calculated by the Kaplan–Meier method, and the difference between the groups was compared using the Log-rank test. Univariate and multivariate analyses using the Cox-regression proportional hazard model were performed to evaluate the prognostic parameters for survival. Result The survival after the lung metastases was influenced by clinical parameters, such as the status and the treatment for both the intrahepatic tumor and the pulmonary lesions. The causes of death were respiratory failure due to metastatic lesions from HCC in 16 patients (20.0%), liver failure caused by the progressive intrahepatic lesions in 54 (67.5%). The mean and median survival times were 684 and 487 days after HCC diagnosis and 264 and 179 days after lung metastases, respectively. Conclusion It was very important to treat the intrahepatic tumor because its worsening was still the major cause of death. The progressive treatment for pulmonary metastases may also be advised for possible prolongation of survival.     

Radiotherapy for lymph node metastases in patients with hepatocellular carcinoma: retrospective study

AIM: This study was conducted to evaluate the effect of external radiation therapy on lymph node metastases from hepatocellular carcinoma (HCC). METHODS: A total 28 patients with cytopathologically proven HCC were subjected to radiation therapy over a 5-year period, and treatment was continued in all cases. All patients underwent irradiation with a total dose ranging between 46 and 60 Gy in daily 2.0-Gy fractions, five times a week. RESULTS: Among the metastatic lesions treated, 18 (64%) and five (18%) patients achieved partial responses and complete responses, respectively. The 1- and 2-year overall survival rates and the median survival time were 53% and 33%, respectively, and 13 months in patients given external beam radiation therapy (EBRT) for a non-palliative, near-cure intent (n = 21). CONCLUSIONS: Although lymph node metastasis from HCC is sensitive to EBRT, the intent of EBRT should be limited to palliation. For palliative purposes, it is useful in treatment with 50 Gy in 25 fractions for these patients.     

Disseminated carcinomatosis of the bone marrow originating from hepatocellular carcinoma. A case report

A 50‐year‐old male patient was admitted to the hospital for persistent high fever and back pain. He was diagnosed with hepatocellular carcinoma (HCC), bone marrow metastasis and disseminated intravascular coagulation (DIC). Despite the diagnosis and treatment, the general condition deteriorated rapidly and he died of cerebral hemorrhage associated with generalized bleeding tendency. Autopsy showed multiple HCC in the liver and systemic metastasis including bone marrow. The case describes a rare complication of HCC with disseminated carcinomatosis of the bone marrow (DCBM) complicated with DIC, with rapid deterioration and death. This is the first case of DCBM from HCC. Physicians need to be aware of DCBM in patients with HCC.     

唑来膦酸钠治疗老年严重骨质疏松症的临床试验

目的探讨唑来膦酸钠治疗老年严重骨质疏松症的临床效果。方法临床收集老年严重骨质疏松症患者120例,随机分为治疗组（60例,平均67．6岁）,给予钙尔奇＋阿法D3＋唑来膦酸钠;对照组（60例,平均66．4岁）,给予钙尔奇＋阿法D3。对两组患者治疗前与治疗2周以后疼痛程度进行评判;测定治疗前和治疗12个月后两组患者髋部及腰椎骨密度;检测治疗前后血钙、磷、碱性磷酸酶（AKP）水平;治疗过程中观察药物不良反应情况。结果排除治疗中3例脱落患者后,治疗组（57例）骨痛缓解快,骨密度改善程度也明显优于对照组（53例）（P〈0．05）。治疗组AKP较治疗前明显下降【（95．2±11．2）VS（147．3±16．1）IU／L;P〈0．05]。两组血钙、血磷及对照组AKP治疗前后无明显改变（P〉0．05）。结论唑来膦酸钠能显著缓解严重骨质疏松症患者骨痛,提高骨密度。     

New treatment for hepatocellular carcinoma

Abstract Although the incidence of hepatocellular carcinoma (HCC) is likely to start falling in many countries following mass vaccination programmes, large numbers of new cases are likely to be seen for many years to come. For the majority of patients, only palliative treatments can be offered. Systemic chemotherapy does not improve survival. Locoregional therapy is widely used and certainly results in a consistent decrease in tumour size, but clear evidence of any improvement in overall survival remains elusive. We have recently described the application of selective internal radiotherapy using ⁹⁰yttrium microspheres. Although response rates by conventional radiological criteria were only modest, several initially inoperable cases became operable and subsequent resection revealed complete pathological remission in some. The resection became possible, not only because of tumour shrinkage, but also because of hypertrophy of the non-tumorous liver. To date, only a small number, probably less than 15% of patients with HCC will be suitable for an attempt at surgical resection and recurrence will occur in more than half of these. We have recently shown that postoperative intra-arterial administration of Lipiodol I¹³¹ may significantly decrease this recurrence rate.     

Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma

AIM： To assess the clinical features and prognosis of 151 patients with extrahepatic metastases from primary hepatocellular carcinoma （HCC）, and describe the treatment strategy for such patients. METHODS： After the diagnosis of HCC, all 995 consecutive HCC patients were followed up at regular intervals and 151 （15.2%） patients were found to have extrahepatic metastases at the initial diagnosis of primary HCC or developed such tumors during the follow-up period. We assessed their clinical features, prognosis, and treatment strategies.
RESULTS： The most frequent site of extrahepatic metastases was the lungs （47%）, followed by lymph nodes （45%）, bones （37%）, and adrenal glands （12%）. The cumulative survival rates after the initial diagnosis of extrahepatic metastases at 6, 12, 24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively. The median survival time was 4.9 mo （range, 0-37 mo）. Fourteen patients （11%） died of extrahepatic HCC, others died of primary HCC or liver failure.
CONCLUSION： The prognosis of HCC patients with extrahepatic metastases is poor. With regard to the cause of death, many patients would die of intrahepatic HCC and few of extrahepatic metastases. Although most of HCC patients with extrahepatic metastases should undergo treatment for the primary HCC mainly, treatment of extrahepatic metastases in selected HCC patients who have good hepatic reserve, intrahepatic tumor stage （T0-T2）, and are free of portal venous invasion may improve survival.