Prognostic benefit in cytoreductive surgery for curatively unresectable hepatocellular carcinoma - comparison to transcatheter arterial chemoembolization

As a strategy for treating advanced hepatocellular carcinoma (HCC), cytoreductive surgery was studied comparing to transcatheter arterial chemoembolization (TACE). Patients who had curatively unresectable intrahepatic multiple HCC with the main tumor 30 mm or more in size were selected for this study. The patients were classified into two groups; i) cytoreductive surgery group (CRS group): 28 patients in whom the main tumor was resected but other cancer nodules remained in the remnant liver, ii) TACE group: 25 patients at Child A grade who underwent TACE, and in whom it was also evaluated retrospectively that the main tumor had been resectable. The cumulative 5-year survival rate was significantly higher in CRS (48.7%) than TACE (17.1%) group. Multivariate analysis revealed that performing cytoreductive surgery was a significant and independent factor to prolong survival. However, 6 of 28 patients died within one year of surgery. Residual tumor thrombus, and the absence or non-effectiveness of adjuvant therapy were significant high risk factors for postoperative death within one year. Conclusively, cytoreductive surgery contributes to a significant lengthening of survival in patients with advanced HCC. To reduce the risk of early postoperative death, the importance of postoperative adjuvant therapy is also recognized.     

A phase I study of chemoembolization with cisplatin, thiotepa, and lipiodol for primary and metastatic liver cancer.

Thirty patients with primary hepatocellular carcinoma or liver metastases were entered into a program of chemoembolization with cisplatin, lipiodol, and escalating doses of thiotepa. Doses of cisplatin were 100/m2, and thiotepa doses ranged from 9 mg/m2 to 24 mg/m2. Two of three patients with ocular melanoma had partial responses in the liver metastases for 3+ and 16 months. In patients with either hepatocellular carcinoma (15 patients) or primary cholangiocarcinoma of the liver (three patients), there were two partial responses, for 22 and 33 months. Five patients had minor responses: four with a 40% reduction in tumor and one with a mixed response. There were four early deaths, which involved sepsis in two patients, respiratory failure in one, and acute myocardial infarction in one. Otherwise, toxicity was tolerable and reversible and included abdominal pain and transient elevation of serum creatinine, bilirubin, and transaminases. Less common toxicities included ototoxicity and peripheral neuropathy. Chemoembolization of the liver with cisplatin, thiotepa, and lipiodol can produce responses, but toxicity can be significant. The recommended starting phase II dose for future studies is thiotepa 24 mg/m2 and cisplatin 100 mg/m2.     

A case of giant hepatocellular carcinoma treatable with radio frequent ablation therapy after effective UFT administration

A 71-year-old man was diagnosed with giant hepatocellular carcinoma (HCC) and hepatitis C cirrhosis at a nearby hospital. Image diagnosis showed no other metastasis, but the tumor was very huge with daughter nodules in the bilateral lobe of the liver. He was thus treated by oral administration of UFT (300 mg/day). Two months later, the giant liver tumor had shrunk remarkably, and the daughter tumors had disappeared. Eight months later, the levels of serum AFP and PIVKA-II had also reduced remarkably. Twelve months following the first treatment, the levels of both serum AFP and PIVKA-II began increasing again, and he was referred to our hospital. CT showed 2 liver tumors, 1 of which showed viability with moderately differentiated hepatocellular carcinoma and the other evidencing necrosis histologically. Radio frequency ablation therapy was performed for 2 tumors by open laparotomy. It was considered that administration of UFT is a useful and safe therapy for far advanced HCC.     

Intra-arterial injection of iodine-131-labeled lipiodol for treatment of hepatocellular carcinoma.

BACKGROUND/AIM: The therapeutic effect of intra-arterial injection of 131-iodine-labeled lipiodol for treatment of hepatocellular carcinoma in palliative or adjuvant settings has been promising. We report, the results of an open study of this therapy in cirrhotic patients with small hepatocellular carcinoma. PATIENTS AND METHOD: Forty patients with hepatocellular carcinoma were given intra-arterial injections of 131-iodine-labeled lipiodol. These injections were repeated if necessary every 3 months. Tumor response (WHO criteria) was determined on CT scans performed after each treatment and every 3 months during the follow-up. Side effects and the cause of death were recorded. Therapeutic response and survival were analyzed. RESULTS: The median number of treatment was 2 (1-4). There was one complete response, 18 partial responses (47.5% response rate); 19 had stable disease and 2 progressions. Overall survival rates (+/-CI 95%) at 1, 2 and 3 years were: 90+/-4.7%, 60.3+/-8%, and 39+/-8.3%, respectively. Median survival was 27 months; 25 patients have died (4-56 months), 8 of tumor progression with a multifocal spread in the liver. Tolerance was good except for 2 patients who develop a fatal drug-related pulmonary insufficiency. CONCLUSION: These data suggest that intra-arterial therapeutic injection of 131-iodine-labeled lipiodol for treatment of hepatocellular carcinoma can provide high rate response and long survival for individuals not eligible for surgery or local treatment.     

可切除大肝癌TACE后手术切除标本的病理研究(英文)

目的探讨可切除大肝癌 TACE 后手术切除标本的病理改变及其意义。方法 2002年1月～2003年1月收治的83例可切除大肝癌患者随机分成术前 TACE 组(36例)与一期手术组(47例),术前 TACE组31例二期切除(二期手术组),5例失去手术切除机会,78例术后病理均证实为肝细胞癌。对比两组标本间主瘤、包膜、子灶、癌栓、肝硬化等病理情况。结果 TACE 组除较一期手术组肿瘤坏死广泛、包膜更完整外,两组间子灶及门脉癌栓发生率、肝外浸润转移无显著差异;TACE 组TACE 后肿瘤体积缩小并不显著,子灶、门脉癌栓完全坏死者少,肝硬化加重。结论可切除大肝癌术前 TACE 不能使肿瘤完全坏死,部分患者耽误手术时机,应严格选择应用。     

可切除大肝癌TACE后手术切除标本的病理研究

To investigate pathological changes in surgically excised specimens from resectable large hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE ) and their significance. From January 2002 to January 2003, 83 patients with resectable large HCC were randomized into two groups: group A, 36 patients who underwent preoperative TACE, and group B, 47 patients who underwent one-stage operation without TACE. Hepatectomy was performed in 31 patients of group A (two-stage operation group) and 47 patients of group B (one-stage operation group). The remaining 5 patients in group A were not operable. The diagnosis of HCC was pathologically confirmed in all 78 patients after hepatectomy. Pathological changes of the excised specimens between the two groups were compared, including main tumors, capsular containment, daughter nodules, tumor thrombi and liver cirrhosis. There were no significant differences in the incidence of daughter nodules, portal vein tumor thrombi (PVTT) and extrahepatic metastasis between the two groups, but the area of main tumor necrosis was more extensive and the rate of encapsulation was higher in two-stage operation group than those in one-stage operation group. No significant shrinkage in the average tumor size was seen in two-stage operation group, where daughter nodules and PVTT necrosis were less, and liver cirrhosis was more serious. Preoperative TACE for resectable large HCC should be used on the basis of strict selection because it does not provide complete tumor necrosis and may result in delayed surgery in some cases.     

Arterial chemoembolization using microencapsulated anticancer drugs]

Selective intra-arterial infusion of ethylcellulose microcapsules containing anticancer drug exerts its therapeutic effects through infarction and sustained drug action (i.e., chemoembolization). Seven hundred and fifty-nine patients with malignant tumors of the liver (310), kidney (177), bladder (100), prostate (41), lung (39), pelvic organs (13), bone (4) and other (75) were treated with single or repeated chemoembolization using microcapsules delivered through percutaneous catheterization as a preoperative or palliative measure. Substantial tumor reduction of 50% was found in 18% of hepatoma, 19% renal cell carcinoma, 54% bladder carcinoma and 54% prostate carcinoma cases. Preoperative chemoembolization facilitated radical surgery for various cancers and significantly improved the survival of patients with locally invasive renal cell carcinoma and bladder carcinoma. Systemic toxic effects were mild, and all patients tolerated the treatment except for one who died of remote embolism to spleen and gallbladder. These results suggested that microcapsule chemoembolization can be successfully applied to a variety of tumors with low morbidity and mortality, and also combined with other treatments in multidisciplinary therapy.     

肝细胞肝癌肾上腺转移的放射治疗

目的探讨肝癌肾上腺转移的放射治疗效果.方法回顾性总结本院22例肝癌肾上腺转移病人,用6MX或15MV光子,进行肾上腺病灶外照射,剂量36～54Gy,中位剂量50Gy.结果14例肾上腺转移病人出现疼痛症状,外放疗后11例(78.6%)疼痛得到完全缓解;2例(14.3%)得到明显缓解,但仍需要止痛药治疗;73%(15/22)病例的肿瘤明显缩小;全部病例中位生存期为10个月;未出现因肾上腺转移灶致死病例;副作用轻微.结论肝细胞肝癌肾上腺转移对放射治疗敏感,50Gy的放疗剂量是比较安全的姑息性治疗.     

可切除大肝癌TACE后手术切除标本的病理研究

目的 探讨可切除大肝癌TACE后手术切除标本的病理改变及其意义。方法 2002年1月～2003年1月收治的83例可切除大肝癌患者随机分成术前TACE组(36例)与一期手术组(47例)，术前TACE组31例二期切除(二期手术组)，5例失去手术切除机会，78例术后病理均证实为肝细胞癌。对比两组标本间主瘤、包膜、子灶、癌栓、肝硬化等病理情况。结果 TACE组除较一期手术组肿瘤坏死广泛、包膜更完整外，两组间子灶及门脉癌栓发生率、肝外浸润转移无显著差异；TACE组TACE后肿瘤体积缩小并不显著，子灶、门脉癌栓完全坏死者少，肝硬化加重。结论 可切除大肝癌术前TACE不能使肿瘤完全坏死，部分患者耽误手术时机，应严格选择应用。     

Transcatheter arterial chemoembolization prolonged survival in a patient with advanced hepatocellular carcinoma accompanied by tumor thrombus of the portal vein trunk

A 50-year-old man having an advanced hepatocellular carcinoma (HCC) was admitted to our institution. An abdominal computed tomogram showed infiltrative mass in the right liver with tumor thrombus invading into the main trunk and contralateral branch of the portal vein. Repetitive transcatheter arterial chemoembolization reduced a tumor size and shrunken portal vein tumor thrombus. The tumor marker levels such as AFP and PIVKA-II decreased. During follow-up, he was diagnosed as having an impending rupture of HCC with acute abdominal pain. He was successfully treated with interventional technique. He died of liver failure 66 months after the first treatment. Although he had a highly advanced HCC with tumor thrombus of the portal vein, repetitive transcatheter arterial chemoembolization therapy may prolong survival.     

Transcatheter arterial embolization using iodized oil (lipiodol) mixed with an anticancer drug for the treatment of hepatocellular carcinoma

The therapeutic results of Lp-TAE (transcatheter arterial embolization with Gelfoam particles preceded by the infusion of a mixture of lipiodol and an anticancer drug via the proper hepatic artery) were evaluated in hepatocellular carcinomas (523 non-resected and 24 resected cases). Excellent therapeutic effects were confirmed not only for the main tumor but also for the the daughter nodules by a histological examination of the liver tissues resected after Lp-TAE. The cumulative 1-year, 2-year and 3-year survival rates in the 523 non-resected cases were 60.4%, 42.9% and 28.0% respectively. These survival rates were all higher than those achieved by Gelfoam TAE. The above results suggest the usefulness of Lp-TAE in the treatment of hepatocellular carcinoma.     

原发性肝癌分子靶向药物临床研究进展

原发性肝癌是世界范围内主要死亡原因之一。尽管各种肝癌治疗方法,如根治性外科切除、肝脏移植、局部消融治疗、动脉化疗栓塞、放疗、系统性化疗等近年来发展迅速,但仍存在临床疗效欠佳、5年生存率低的问题。近10年来,随着对肝癌基础研究的深入,肝癌发生发展信号转导通路的明确,以索拉非尼（Sorafenib）为代表的分子靶向药物在进展期肝癌治疗中日益受到重视并广泛应用,延长了进展期肝癌的生存时间,改善了患者的生存质量。本文就肝癌分子靶向治疗的研究进展及应用现状作一综述。     

Laparoscopic microwave coagulation therapy for small hepatocellular carcinoma on the liver surface

Six patients with small size (< or =2.0 cm in diameter) hepatocellular carcinoma (HCC) on their liver surface underwent laparoscopic microwave coagulation therapy (LMCT) in our institute. All cases showed complete necrosis after LMCT alone and there were no major complications during the LMCT. During the follow-up period, one patient had recurrent HCC at the LMCT-treated lesion site and two patients had lesions at sites distant to the LMCT-treated site. Two out of these three patients had presented with severe liver dysfunction at admission and died within the follow-up period. LMCT is believed to be a useful and safe treatment for small size HCC on the liver surface, and treatment can achieve complete tumor necrosis. However, in severe liver dysfunction, the use of LMCT may have a negative influence on patient survival.     

Chemoembolization with degradable starch microspheres in malignant hepatic tumors

A new method of chemoembolization with degradable starch microspheres (DSM) was used for patients with malignant hepatic tumors. DSM, 40-45 micron in diameter, which are degraded by serum amylase, temporarily obstruct arterial blood flow at the arteriolar capillary bed. Experimental studies have demonstrated that such occlusion enhances the regional uptake and reduces systemic exposure to simultaneously administered arterial anticancer drugs. Transcatheter chemoembolization with DSM was performed in 14 cases of hepatocellular carcinoma and 8 cases of metastatic liver cancer. Adriamycin or Mitomycin C mixed with DSM was injected into the patients with hepatocellular carcinoma or metastatic liver cancer, respectively, through the proper hepatic artery. The therapeutic effect of this chemoembolization was evaluated by the change in tumor size measured by angiography or computed tomography. In hepatocellular carcinoma, tumor regression of over 50% was observed in 5 of 14 patients. Elevated serum AFP level of more than 200 ng/ml was decreased in all 6 cases. In metastatic liver cancer, tumor regression of over 50% was observed in 4 of 8 cases. Although half of the patients had transient pain within 2 hours, no major side effects such as bone marrow suppression and hepatotoxicity were observed. Our results suggest that chemoembolization with DSM can be effectively used in the treatment of malignant hepatic tumors.     

肝细胞肝癌放射治疗研究进展

肝细胞肝癌（hepatocellular carcinoma,HCC）是世界范围内癌症死亡率较高的肿瘤之一。肝切除术（partial hepatectomy）是重要的治疗手段,然而,许多患者因肿瘤分期晚或潜在的慢性肝病和/或肝硬化不能接受肝切除术或肝移植术(liver transplantation)。此类患者,目前可选择肝动脉栓塞化疗（transarterial chemoembolization,TACE）、射频消融（radiofrequency ablation,RFA）、放射治疗、靶向治疗及免疫治疗等方法。肝癌诊断、治疗方式、对肝脏辐射耐受性的生物学理解和放疗技术的进步使得肝癌放射治疗的有效性和安全性都在不断提高,肝癌患者的生存和预后不断改善。     

Radiation therapy for adrenal gland metastases from hepatocellular carcinoma

BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from hepatocellular carcinoma. However, it has been the subject of few studies, and the optimal treatment remains unclear. Methods previously tried for the management of adrenal gland metastasis of hepatocellular carcinoma included surgical resection, transarterial chemoembolization or percutaneous ethanol injection, on the basis of case reports. External beam radiation therapy has seldom been applied for patients with adrenal gland metastases. METHODS: We retrospectively studied 22 patients with adrenal metastases from hepatocellular carcinoma who were treated with limited-field external beam radiation therapy. The radiation dose to the adrenal lesion ranged from 36 to 54 (median 50) Gy, while the intrahepatic lesions were treated with either surgical resection or transarterial chemoembolization. RESULTS: Among the 14 patients who had pain related to adrenal metastases, 11 (78.6%) had complete pain relief without medication that lasted until death. Two (14.3%) patients had marked pain relief, but still required analgesics. Partial responses were observed in 73% of the patients. The median survival period for all patients was 10 months. No patient died from complications related to adrenal metastasis. Adverse effects were mild. CONCLUSION: Adrenal metastases from hepatocellular carcinoma are sensitive to radiation treatment. Radiation therapy with 50 Gy for adrenal gland metastases is a good palliative therapy with reasonable safety.     

肝细胞肝癌脑转移临床特性和预后分析

目的：分析肝细胞肝癌（hepatocellular carcinoma,HCC）脑转移的临床特点和预后相关因素。方法：回顾性研究2004—0430—2011-12-01我院在放疗科诊治的32例HCC脑转移患者,其中27例接受脑部肿瘤的放射治疗,随访患者的生存情况。结果：32例患者中,27例患者出现中枢神经系统症状,5例无症状即发现颅脑转移。脑转移到死亡的中位生存期为（4．53±2．12）个月,颅脑HCC后到脑转移的中位时间为14．5个月,1年生存率为15．6％。单因素分析显示,颅脑症状（P=0．008）、RPA（P=0．002）、Child-Pugh肝功能分级（P〈0．01）及肝内病灶控制情况（P=0．040）与生存时间相关;多因素分析则显示,颅脑症状、颅内转移灶数目（P=0．027）和是否接受过脑转移灶放疗（P=0．001）是影响患者预后的主要因素。20例脑转移患者已经出现肺转移,21例患者死于肝内病灶未控,5例患者因脑转移灶未能控制而死亡。结论：HCC脑转移患者生存时间短,大部分患者以伴有颅外转移灶,颅内症状、肝功能分级、颅内病灶个数和是否放疗是预后主要因素。     

Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma.

PURPOSE: To evaluate the safety and efficacy of proton beam radiotherapy (PRT) for hepatocellular carcinoma. PATIENTS AND METHODS: Eligibility criteria for this study were: solitary hepatocellular carcinoma (HCC); no indication for surgery or local ablation therapy; no ascites; age >/= 20 years; Zubrod performance status of 0 to 2; no serious comorbidities other than liver cirrhosis; written informed consent. PRT was administered in doses of 76 cobalt gray equivalent in 20 fractions for 5 weeks. No patients received transarterial chemoembolization or local ablation in combination with PRT. RESULTS: Thirty patients were enrolled between May 1999 and February 2003. There were 20 male and 10 female patients, with a median age of 70 years. Maximum tumor diameter ranged from 25 to 82 mm (median, 45 mm). All patients had liver cirrhosis, the degree of which was Child-Pugh class A in 20, and class B in 10 patients. Acute reactions of PRT were well tolerated, and PRT was completed as planned in all patients. Four patients died of hepatic insufficiency without tumor recurrence at 6 to 9 months. Three of these four patients had pretreatment indocyanine green retention rate at 15 minutes of more than 50%. After a median follow-up period of 31 months (16 to 54 months), only one patient experienced recurrence of the primary tumor, and 2-year actuarial local progression-free rate was 96% (95% CI, 88% to 100%). Actuarial overall survival rate at 2 years was 66% (48% to 84%). CONCLUSION: PRT showed excellent control of the primary tumor, with minimal acute toxicity. Further study is warranted to scrutinize adequate patient selection in order to maximize survival benefit of this promising modality.     

MRI、DSA和碘油CT联合应用对肝硬化结节癌变的诊断价值

背景与目的:肝硬化结节癌变是肝硬化转变成为肝癌的必经阶段,早期发现和早期干预对提高患者的生存率具有重要意义。本研究探讨联合应用MRI、DSA和碘油CT对肝硬化结节癌变诊断价值,旨在早期发现肝硬化结节癌变。方法:收集经病理证实的肝硬化癌变病例18例,所有患者均行MRI、DSA和和碘油CT检查,分析MRI、DSA和碘油CT对肝硬化结节恶变的诊断价值。结果:18例患者中共有31个病灶,其中MRI发现病灶29个,肿瘤病灶T1WI呈低信号12个,高信号9个,等信号8个;T2WI呈稍高信号20个,等信号9个;DWI呈高信号23个;三期动态增强扫描呈"快进快出"共18个,"快进慢出"3个,持续强化3个;另有5个病灶因T1WI呈高信号,强化表现观察不满意。DSA发现27个病灶,表现为肿瘤血管生成、血管扭曲、血供增多、肿瘤染色;2周后复查碘油CT,31个病灶均有碘油沉积。结论:MRI、DSA和碘油CT联合应用能提高肝硬化结节癌变的诊断准确性,从而早期发现肝硬化结节癌变。     

肝癌肝动脉栓塞化疗术并发碘油肺栓塞的临床观察

探讨肝癌肝动脉栓塞化疗术并发碘油肺栓塞的发病机制、临床表现、治疗方法及预防措施。分析肝癌行TACE术后发生碘油肺栓塞7例患者的术前肝脏CT、术中DSA检查、术中所用的碘油量及化疗药物剂量、术中术后的临床表现、辅助检查及临床治疗情况。患者出现不同程度的咳嗽、咯血、呼吸困难和低氧血症,胸片可见片状密度增高影。给予吸氧、扩张支气管、必要时呼吸机辅助呼吸及其他支持治疗后好转。随访观察20d～2个月,复查胸片正常。7例病例病灶直径约>10cm,存在肝动脉-肝静脉瘘的5例,碘油用量>20mL的5例。初步研究结果提示,碘油肺栓塞常发生在巨块型肝癌,且多存在肝动脉-肝静脉瘘,碘油用量多>20mL,术中正确处理可减少此类并发症的发生。