Targeting liver tumors with hyperthermia: ferromagnetic embolization in a rabbit liver tumor model

BACKGROUND AND OBJECTIVES: Ferromagnetic embolization hyperthermia (FEH) consists of arterially embolizing liver tumors with ferromagnetic particles, and then applying an external alternating magnetic field to generate hysteretic heating within the embolized particles. The objective of this study was to assess the ability of FEH to selectively target liver tumors with hyperthermia. METHODS: Twenty rabbits containing hepatic VX2 carcinomas were arterially infused with ferromagnetic particles suspended in lipiodol, and then exposed to an external alternating magnetic field. Temperatures in the tumor, normal hepatic parenchyma (NHP), and rectum were recorded. Tumour and NHP were chemically analyzed for iron content, which was then correlated with the observed heating rates. RESULTS: The mean tumor-to-NHP iron concentration ratio was 5.3:1 (P < 0.001, N = 20). The mean tumor heating rates were 3.0-11.5 times greater than those in the NHP (P < 0.001, N = 20). After 5 min of heating, the greatest increase in mean tumor temperature was 11.0 degrees C and the greatest increase in mean NHP temperature was 1.3 degrees C. There was a positive relationship between tumor iron concentration and heating rate (correlation coefficient = 0.82, P < 0.001, N = 20). A tumor iron concentration of 2-3 mg/g resulted in tumor heating rates of 0.5-1.0 degrees C/min. CONCLUSIONS: Hepatic arterial infusion of lipiodol containing ferromagnetic particles can result in excellent targeting of liver tumors with hyperthermia on the subsequent application of an external alternating magnetic field. The promising results of this study warrant further investigation of FEH as a potential treatment for advanced liver cancer.     

腹腔镜辅助联合肝脏离断和门静脉结扎的二步肝切除术治疗原发性肝癌的安全性和疗效评价

目的探讨腹腔镜辅助联合肝脏离断和门静脉结扎的二步肝切除术（associating liver partition and portal vein ligation for staged hepatectomy , ALPPS ）治疗原发性肝癌的安全性和疗效。方法回顾性分析2013年12月本院收治的一例巨块型肝癌患者以腹腔镜辅助ALPPS方法切除肿瘤的临床资料。第1步在腹腔镜下结扎门静脉右支并离断左肝内外叶;第2步在第1次术后第8天,评估剩余肝脏体积能满足机体要求后行右半肝的扩大切除术,同时对患者围术期的临床指标和随访资料进行分析。结果第1次手术出血50 ml,手术时长225分钟。第2次手术出血700 ml,手术时长335分钟。切除右肝三叶大小约24．0 cm×22．0 cm×15．0 cm,重量2．7 kg,肿瘤大小约18．0 cm×16．0 cm×14．0 cm,残余肝大小约15．0 cm×13．0 cm×8．0 cm。术后病理结果为原发性肝细胞癌。术后患者出现胆漏,经保守治疗后治愈。术后随访2个月,残余肝再生体积达约1200 ml,AFP降至150 ng／ml,未发现肿瘤复发转移。术后随访至32个月,再次评估残余肝再生体积达约1300 ml,AFP 16 ng／ml,未发现肿瘤复发转移,无疾病生存期达32个月。结论腹腔镜辅助ALPPS手术可作为残肝体积不足的一些较晚期肝癌患者的治疗选择。     

Lymphocytic infiltration surrounding liver metastases from colorectal cancer

BACKGROUND AND OBJECTIVES: Tumor infiltrating lymphocytes (TILs) have been recognized as a tumor-host reaction in various primary neoplasms. Although several studies reported TILs surrounding metastatic liver tumors, to the authors' knowledge few evaluations of the clinical significance of such features in patients with colorectal liver metastases have been carried out. METHODS: Forty-one patients who underwent initial hepatic resection for liver metastases from colorectal cancer were studied. Lymphocytic infiltration surrounding metastatic liver tumor was graded as weak or dense according to the mean number of TILs from 10 high-power microscopic fields (< or =50 or >50/HPF). RESULTS: Dense lymphocytic infiltration between the metastatic tumor and hepatic parenchyma was seen in 18 of 41 patients (44%). Histologically, tumor invasion of the portal vein was rare in patients with dense TILs (12%) compared with patients with weak TILs (36%). Patients with dense TILs survived longer than patients with weak TILs after hepatic resection (P = 0.013). Multivariate analysis using the Cox proportional hazard model identified this pathological variable as a significant independent prognostic factor after hepatic resection. CONCLUSIONS: The extent of lymphocytic infiltration between the metastatic nodule and hepatic parenchyma may reflect host defensive activity in the liver and is closely related to prognosis in patients who underwent hepatic resection for liver metastases from colorectal cancer.     

Liver function after irradiation based on computed tomographic portal vein perfusion imaging

PURPOSE: To determine whether individual and regional liver sensitivity to radiation could be assessed by measuring liver perfusion during a course of treatment using dynamic contrast-enhanced computed tomography scanning. METHODS AND MATERIALS: Patients with intrahepatic cancer undergoing conformal radiotherapy underwent dynamic contrast-enhanced computed tomography (to measure perfusion distribution) and an indocyanine extraction study (to measure liver function) before, during, and 1 month after treatment. We hoped to determine whether the residual functioning liver (i.e., those regions showing portal vein perfusion) could be used to predict overall liver function after irradiation. RESULTS: Radiation doses from 45 to 84 Gy resulted in undetectable regional portal vein perfusion 1 month after treatment. The volume of each liver with undetectable portal vein perfusion ranged from 0 to 39% and depended both on the patient's sensitivity and on dose distribution. There was a significant correlation between indocyanine green clearance and the mean of the estimated portal vein perfusion in the functional liver parenchyma (p < 0.001). CONCLUSION: This study reveals substantial individual variability in the sensitivity of the liver to irradiation. In addition, these findings suggest that hepatic perfusion imaging may be a marker for liver function and has the potential to be a tool for individualizing therapy.     

Phase I Trial of Selective Internal Radiation Therapy for Chemorefractory Colorectal Cancer Liver Metastases Progressing After Hepatic Arterial Pump and Systemic Chemotherapy

IntroductionThis prospective study assessed the safety and outcomes of selective internal radiation therapy (SIRT) using yttrium-90 (⁹⁰Y) resin microspheres as a salvage therapy for liver-predominant metastases of colorectal cancer in patients with documented progression after hepatic arterial chemotherapy (HAC) and systemic chemotherapy.Patients and MethodsWe recruited 19 patients who had received a mean of 2.9 prior lines of chemotherapy and ≥ 1 line of HAC. Dose-limiting toxicities (grade 3 or higher) were catalogued using Common Terminology Criteria for Adverse Events version 3.0. At 4 to 8 weeks and 3 to 4 months post SIRT, responses were assessed by carcinoembryonic antigen (CEA), and quantitative imaging using Response Evaluation Criteria in Solid Tumors (RECIST) and PET Response Criteria in Solid Tumors (PERCIST). Liver progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) were calculated using Kaplan-Meier methodology.ResultsMedian follow-up was 31.2 months after SIRT. Within 6 weeks of SIRT, 3 patients (15.8%) experienced grade 3 toxicity. There was no incidence of radiation-induced liver disease. Responses by RECIST, PERCIST, and CEA were, respectively, 0%, 20%, and 32% at 4 to 8 weeks and 5%, 33%, and 21% at 3 to 4 months post SIRT; 53% of patients had stable disease (by RECIST) at 3 to 4 months. Of 19 patients, 4 (21.1%) had liver ablation, 9 (47%) received additional HAC, and 17 (89%) received systemic chemotherapy after SIRT. Median LPFS, PFS, and OS after SIRT were 5.2 months, 2.0 months, and 14.9 months, respectively.ConclusionSIRT was well tolerated and did not prohibit subsequent treatment, resulting in a median OS of 14.9 months in this heavily pretreated population.     

合并门静脉癌栓的原发性肝癌的手术治疗及预后分析

目的:评价手术治疗合并门静脉癌栓(PVTT)的原发性肝癌(PHCC)的疗效和影响患者术后生存的预后因素。方法:对26例在我院行手术治疗的PHCC合并PVTT患者的资料进行回顾性分析并进行随访,计算术后生存率和中位生存时间,单因素分析11项临床病理因素对术后生存时间的影响。结果:手术采用肝癌切除术联合门静脉癌栓摘除术。术后总的1,2,3年生存率为50%,16.7%和8.3%,中位生存时间为13个月。术后定期行门静脉或肝动脉灌注化疗,患者的中位生存时间为16.1个月,而单纯手术者为7.2个月,两者差异有显著性(P=0.001)。单因素分析提示术后是否化疗和肿瘤大小(以10cm为界限)对术后生存有影响。结论:手术治疗可明显提高PHCC合并PVTT患者的生存时间,对没有禁忌证者应为首选。术后是否化疗和肿瘤大小影响术后生存时间,术后应常规进行化疗。     

Results of three-dimensional conformal radiotherapy and thalidomide for advanced hepatocellular carcinoma

PURPOSE: To evaluate the effectiveness of three-dimensional conformal radiotherapy and thalidomide in the treatment of advanced hepatocellular carcinoma. METHODS: Between 1999 and 2003, 121 patients (mean age, 54.4 +/- 12.4 years; range, 20-81 years) with advanced hepatocellular carcinoma received three-dimensional conformal radiotherapy and thalidomide. Radiation was delivered in 1.5 Gy fractions twice daily for 5 days a week, for a total dose of 45-75 Gy. Mean treatment volume was 429.52 +/- 408.50 cm(3) (range, 26.89-2284.82 cm(3)). Thalidomide was given concomitantly: 200 mg/day in 109 patients, 300 mg/day in 8 patients and 400 mg/day in 4 patients. Treatment responses, survival rates and factors affecting survival were analyzed. RESULTS: Treatment responses were observed in 61% of the patients. Liver cirrhosis (P = 0.001) and tumor size (P = 0.001) significantly affected the tumor responses. Overall survival at 6, 12 and 24 months was 84.8, 60.0 and 44.6%, respectively. On univariate analysis, liver cirrhosis (P = 0.003), Karnofsky performance status (P = 0.007), tumor size (P < 0.001), portal vein tumor thrombosis (P < 0.001) and alpha-fetoprotein level (P = 0.003) were shown to significantly affect survival. On multivariate analysis, only thrombosis (P = 0.039) and alpha-fetoprotein level (P = 0.006) were shown to be factors affecting survival. CONCLUSIONS: Three-dimensional conformal radiotherapy with thalidomide seems to be effective in the treatment of advanced hepatocellular carcinoma.     

The relationship between hypoalbuminaemia, tumour volume and the systemic inflammatory response in patients with colorectal liver metastases

The relationship between hypoalbuminaemia, tumour volume and C-reactive protein was examined in patients with colorectal liver metastases (n=57). On multiple regression analysis, albumin concentrations were independently associated with C-reactive protein (r=0.56, P<0.001) but not percentage hepatic replacement (P=0.34). These results show that hypoalbuminaemia is associated with the presence of a systemic inflammatory response rather than tumour volume in patients with colorectal liver metastases.     

Tumor and liver drug uptake following hepatic artery and portal vein infusion

Anatomic dye injection studies of the blood supply of colorectal hepatic metastases suggest that tumors are supplied predominantly by the hepatic artery. Using 13N amino acids with dynamic gamma camera imaging in patients with colorectal hepatic metastases, it has been shown that hepatic artery infusion results in a significantly greater nutrient delivery to tumor compared with portal vein infusion. However, direct measurements of drug levels in tumor following hepatic artery and portal vein infusion in humans have not previously been reported. Patients with metastatic colorectal cancer confined to the liver received fluorodeoxyuridine (FUdR) through the hepatic artery or through the portal vein. All patients had previously failed systemic chemotherapy. Five patients with hepatic artery catheters were matched (by age, serum lactic dehydrogenase levels, percent hepatic replacement, and tumor size) with five patients with portal vein catheters. At operation, 3H-FUdR (1 microCi/kg) and 99mTc-macroaggregated albumin (MAA) (6 mCi) were injected into the hepatic artery or portal vein. Liver and tumor biopsies were obtained two and five minutes later. 3H and 99mTc were measured per gram tissue by scintillation and gamma counting. The mean liver levels following hepatic artery infusion (23.9 +/- 11.4 nmol/g) and portal vein infusion (18.4 +/- 14.5 nmol/g) did not differ. However, the mean tumor FUdR level following hepatic artery infusion was 12.4 +/- 12.2 nmol/g, compared with a mean tumor FUdR level following portal vein infusion of 0.8 +/- 0.7 nmol/g (P less than .01). This low level of tumor drug uptake after portal vein infusion of FUdR predicts minimal tumor response to treatment via this route. Thus, regional chemotherapy for established colorectal hepatic metastases should be administered through the hepatic artery.     

Combined hepatic-artery and portal-vein chemoembolization for colorectal cancer metastatic to the liver

The purpose of the study was to evaluate the results of combined (hepatic artery and portal vein) oily chemoembolization (OCE) in patients with unresectable colorectal liver metastases. Courses of combined OCE were given to 45 patients (1990-2000). For arterial OCE (n = 150), 40-100 mg doxorubicin mixed with 10-15 ml iodized oil and gelatin sponge was used. OCE of the portal vein (n = 118) included injection of doxorubicin-in-oil without sponge. Response to treatment (partial tumor decrease or stabilization) was reported in 80%. Serious complications occurred in 3 patients (7%) but there was no mortality. The mean and median survival rates for those patients who died were 20.2 and 17 months, respectively. The 1-, 2-, and 3-year survival rates were 83, 40 and 14%, respectively. These results were significantly better than those for arterial OCE alone or hepatic arterial infusion. Combined (arterial and portal vein) OCE with doxorubicin appears the most effective locoregional treatment for unresectable colorectal liver metastases.     

NRP-1在肝细胞癌组织中的表达及其临床意义

目的 明确神经纤毛蛋白质1(NRP-1)在肝细胞癌(HCC)组织中的表达情况及其临床意义.方法 收集151例HCC组织和89例正常肝组织标本,应用免疫组织化学染色法检测其中NRP-1蛋白的表达情况.单因素及多因素统计分析NRP-1表达与HCC患者临床病理指标的关系,并以生存分析比较不同NRP-1表达水平患者的生存情况.结果 失访或随访期间因非HCC疾病死亡的病例共11例,最终进入研究的有效病例为140例.NRP-1在HCC组织和正常肝组织中的阳性表达率分别为65.00％、35.96％,差异有统计学意义(x2=18.843,P＜0.001).按照NRP-1的表达水平,将140例HCC患者分为阴性表达组49例,阳性表达组91例.单因素分析结果显示,NRP-1在HCC中的表达与肿瘤数目(x22=8.025,P=0.005)、TNM分期(x2=26.467,P ＜0.001)、分化程度(x2=15.296,P ＜0.001)、门脉侵袭(x2=9.054,P=0.003)以及肝静脉侵袭(x2=5.928,P=0.015)有关.多因素分析结果显示,TNM分期(OR=1.392,95％ CI为1.121 ～1.730,x2=8.950,P=0.003)、分化程度(OR=1.469,95％ CI为1.102 ～1.958,x2 =6.862,P =0.009)、门脉侵袭(OR=1.829,95％ CI为1.157 ～ 2.893,x2=6.665,P=0.010)及肝静脉侵袭(OR =2.161,95％ CI为1.172 ～3.987,x2=6.084,P=0.014)是NRP-1表达的影响因素.NRP-1阴性组HCC患者的中位生存时间显著长于阳性组患者(44个月∶23个月),差异有统计学意义(x2=21.922,P＜0.001).结论 NRP-1在HCC组织中呈过表达趋势,与HCC的恶性程度密切相关,其表达增高提示患者预后不良.     

Perfusion of colorectal hepatic metastases. Relative distribution of flow from the hepatic artery and portal vein

The importance of portal circulation in the delivery of drugs and nutrients to colorectal hepatic metastases is controversial. Using 13N (nitrogen 13) amino acids and ammonia with dynamic gamma camera imaging, we demonstrate, for the first time in human beings, a quantitative advantage of hepatic artery compared with portal vein infusion. Eleven patients were studied by hepatic artery injection, five patients were studied by portal vein injection, and two patients had injections through both routes. Data collected from the liver for 10 minutes after rapid bolus injection of 13N L-glutamate, L-glutamine, or ammonia were compared with 99mTc (technetium) macroaggregated albumin (MAA) images produced after injection through the hepatic artery or portal vein at the same session. Tumor regions defined from 99mTc sulfur colloid scans were compared with nearby liver areas of similar thickness. For the 13N compounds, the area-normalized count rate at first pass maximum (Qmax) and the tissue extraction efficiency were computed. The tumor/liver Qmax ratios for MAA and 13N compounds were highly correlated. Both tumor and liver extracted more than 70% of the nitrogenous compounds. The tumor/liver Qmax ratios reflect the relative delivery of injected tracer per unit volume of tissue. After hepatic artery injection the Qmax ratio was 1.03 +/- 0.33 (mean +/- SD), significantly exceeding the Qmax ratio of 0.50 +/- 0.34 after portal vein injection (P less than 0.003). Therefore, more than twice as much of a nutrient substrate is delivered per volume of tumor relative to liver by the hepatic artery as by the portal vein; the high extraction efficiency demonstrates that the hepatic artery flow is nutritive; and the delivery of substance in solution (such as nutrients or drugs) to tumor and liver tissue correlates with the distribution of colloids such as macroaggregated albumin after hepatic arterial and portal venous injection.     

Prediction of the risk of hepatic failure in patients with portal vein invasion hepatoma after hepatic resection.

AIM: Hepatic failure can develop after curative hepatectomy in patients with a hepatocellular carcinoma (HCC) invading the portal vein, because of cirrhosis and excessive tissue loss. This study aimed to identify the risk factors for hepatic failure in such patients. METHOD: Forty patients with an HCC invading the portal vein underwent curative hepatectomy from January 1995 to June 2003. Eight patients developed hepatic failure and died within 3 months. Possible risk factors for this were analysed using univariate and multivariate regression. These included the liver function index, surgical blood loss, tumour pattern, portal hypertension, estimated residual liver volume measured by computed tomography (ERLV(CT)) and estimated residual liver volume using the indocyanine green (ICG) retention rate at 15 min (ERLV(ICG15)). RESULTS: The ERLV(CT) smaller than the ERLV(ICG15) and presence of portal hypertension were independent risk factors for post-hepatectomy hepatic failure. CONCLUSION: Having portal vein invasion HCC with portal hypertension or an ERLV(CT) less than an ERLV(ICG15) are significant predictors of post-hepatectomy hepatic failure. These factors are important considerations for patients with portal vein invasion HCC who could undergo curative hepatic resection.     

Optimised radiological diagnosis of hepatic fungal infection during the treatment of leukemia

Hepatic fungal infection is a frequent complication in patients receiving intensive chemotherapy for acute leukaemia. Hepatic lesions may be detected using computerised tomographic (CT) scans, but there is no standardised CT protocol for the diagnosis and follow-up of hepatic fungal infection. We therefore retrospectively analysed the number and the volume of hepatic fungal lesions in 24 CT of 20 consecutive patients treated for acute leukaemia during late-arterial and porto-venous phase. The mean number of lesions per patient was 31 (range: 3-105) in the late-arterial and 26 (3-81) in the porto-venous CT (P = 0.026). The mean total volume of all lesions was 6.45 ml in the late-arterial and 4.07 ml in the porto-venous CT representing a 1.6fold difference between the two CT scans (P = 0.008). The total volume of the lesions negatively correlated to the absolute contrast difference between liver parenchyma and liver vein (Pearson correlation, r = -0.62; P = 0.002). In conclusion, the late-arterial CT provides a superior distinction of hepatic lesions due to a delayed perfusion of the outer rim of the fungal lesions resulting in an extended visibility. The late-arterial CT is superior to the porto-venous CT for initial diagnosis and follow-up of hepatic fungal infection.     

The combination of degradable starch microspheres and angiotensin II in the manipulation of drug delivery in an animal model of colorectal metastasis.

Both biodegradable emboli and pharmacological agents can enhance regional therapy for hepatic targeting. Using a rat model with similar haemodynamic characteristics to human colorectal liver tumour and a radio-labelled marker of similar molecular weight to Adriamycin, we have combined the two approaches to see if the effect was addictive. Following induction of liver tumour in male hooded rats by intrahepatic injection of HSN sarcoma cells, the relative distribution of marker, 99mTc methylene diphosphonate (MDP), was studied in three groups given the following by injection into the hepatic artery. (1) Saline (Control) + MDP; (2) Degradable Starch Microspheres (DSM) + MDP; and (3) Angiotensin II + DSM + MDP. Both Degradable Starch Microspheres alone (P less than 0.001) and Degradable Starch Microspheres + Angiotensin II (P = 0.003) significantly increased the retention of marker in liver and tumour at 1 min following injection, with a 12-fold improvement over controls, but the tumour:liver ratio was unaltered. By 90 min the MDP levels in normal hepatic parenchyma had returned to control values. There was relatively less washout with significant retention in tumour tissue in both DSM (P = 0.03) and combination treated animals (P = 0.001), with a significantly improved (P = 0.001) tumour to liver ratio (5.22:1) in combination treated animal relative to those treated with DSM alone.     

原发性肝癌大分割三维适形放疗的预后因素分析

目的评价大分割三维适形放射治疗(3DCRT)对原发性肝癌的疗效,探讨其预后影响因素。方法对128例原发性肝癌进行大分割3DCRT。按UICC/AJCC分期,T3期83例,T4期45例,均为N0。合并有门脉癌栓(PVTT)34例,无PVTT94例。根据肝硬化Child-Pugh分级,A级108例,B级20例。大体肿瘤体积(GTV)为(458.92±429.8)cm3,中位值304.5cm3;每次分割剂量4~8Gy,照射次数7~15次;肿瘤剂量38~74Gy,每周3次,隔日一次。结果7例患者大分割3DCRT后3个月内死亡,诊断为放射性肝病,未能评价疗效。总有效(CR+PR)率为55.4%(67/121),1,2,3年生存率分别为65.0%、43.3%和33.1%。T分期、GTV、PVTT和Child-Pugh分级对预后的影响有统计学意义(P均<0.01),GTV和Child-Pugh分级是独立的预后因子(P=0.044和0.015,RR=1.001和2.528)。结论UICC/AJCCT分期和PVTT对肝癌大分割3DCRT的生存率有影响,GTV和Child-Pugh分级是独立预后因子。     

原发性肝癌的介入综合治疗及其预后影响因素

目的评价原发性肝细胞肝癌肝动脉化疗栓塞（TACE）为主的综合治疗,分析、筛选与预后相关的因素。方法141例原发性肝细胞肝癌分别采用TACE治疗、TACE＋手术切除、TACE＋PEI治疗和TAI治疗。根据多因素回归模型,对患者年龄、性别、血清AFP、ALT、HBsAg、肝功能Child分级、治疗方式、肿瘤大小及数目、血清白蛋白水平、门静脉癌栓、肿瘤病理类型和血清HBeAg进行预后分析。结果本组患者的总体中位生存时间为19个月,平均生存23,59个月。1、2、3、5年生存率分别为63．9％、44．5％、25．8％和7．4％。多因素分析显示,患者年龄、肝功能Child分级、治疗方式、门静脉癌栓和肿瘤病理类型与TACE综合治疗预后有关（X^2=45．993,P=0．0001）。结论原发性肝细胞肝癌介入综合治疗安全、有效。患者年龄、肝功能Child分级、门静脉癌栓和肿瘤病理类型是影响介入综合治疗预后的危险因素,治疗方式是影响预后的保护性因素。     

A combination therapy with transarterial chemo-lipiodolization and systemic chemo-infusion for large extensive hepatocellular carcinoma invading portal vein in comparison with conservative management

PURPOSE: Hepatocellular carcinoma (HCC) invading the portal vein is a medical challenge. We evaluated the therapeutic efficacy of a combination of transarterial and systemic chemo-infusion for large HCC with portal vein thrombosis (PVT) compared with conservative management. PATIENTS AND METHODS: This was a case-control cohort study of 103 consecutive patients with Child-Pugh class A who had a large (>10 cm) HCC with PVT. The patients were assigned to receive either combined transarterial epirubicin (50 mg/m(2)) plus cisplatin (60 mg/m(2)) chemo-lipiodolization and systemic 5-fluorouracil (200 mg/m(2)) chemo-infusion (ECF regimen) at monthly intervals (n=80) or conservative management (n=23). RESULTS: The objective tumor response (21.3 vs. 0%, P=0.011) and overall survival (8.7 vs. 3.5 months, P<0.001) were significantly better in the treatment group than in the conservative group. The prognostic factors for survival were tumor type (P=0.007), bilobar involvement (P=0.001), distant metastasis (P=0.009) and objective tumor response (P<0.001) for the treatment group. Survival benefits with the treatment were also maintained in each subgroup after stratification of these variables. CONCLUSIONS: This study suggests that when the hepatic function is preserved, a therapeutic strategy could be more beneficial than conservative management for such a large extensive HCC. As a therapeutic option, a combination therapy using ECF regimen may provide a significantly better tumor response and survival benefit in patients with large HCC invading the portal vein.     

肝癌介入治疗的相关因素与死亡时间关系探讨

目的 分析肝癌介入治疗（TACE）几个因素与死亡时间的关系。方法 随机选择经过TACE治疗,在不同时间内死亡者195例。将患者的年龄、性别、灌注的化疗药物和碘油的剂量、术前肿瘤的大小、形态、转移、门静脉癌栓、术后复发、肝功能和AFP共分为15项变量,统计学采用Cox回归分析和Cox逐步回归分析方法。结果 治疗后6个月和12个月死亡率为49．7％和75．9％。死亡时间与门静脉癌栓、弥漫型肿瘤和多发性肿瘤有明显相关（P＜0．05,P＜0．0001）;肿瘤形态中弥漫型与多发性、单结节和巨块型间相关显著（P＜0．05,P＜0．001,P＜0．001）,死亡时间与其他各组在统计学上无明显相关性（P＞0．05）。患者死于肝昏迷为27．2％,消化道大出血为36．9％,肝功能衰竭为23．1％,全身衰竭为5．1％,其他为7．2％。结论 对部分肝功能不良的患者,TACE有加重肝功能损害和加速患者死亡的作用。对于肝癌患者,特别是有门静脉癌栓、多发性和弥漫型患者,治疗时应首先考虑全身和肝功能情况、肝脏对药物的耐受性,严格掌握时机、方法和剂量,术后保肝十分重要。     

A phase I-II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver.

There are no satisfactory treatment options for patients with ocular melanoma metastatic to liver, and after liver metastases are identified, median survival is only between 2 and 7 months. Because liver metastases are the sole or life-limiting component of disease in the vast majority of patients who recur, we reasoned that complete vascular isolation and perfusion of the liver might result in clinically meaningful regression of disease. Between September 1994 and July 1999, 22 patients (13 women and 9 men; mean age, 49 years) with ocular melanoma metastatic to liver were treated with a 60-min hyperthermic isolated hepatic perfusion (IHP) using melphalan alone (1.5-2.5 mg/kg, n = 11) or with tumor necrosis factor (TNF, 1.0 mg, n = 11). Via a laparotomy, IHP inflow was via the hepatic artery alone (n = 17) or hepatic artery and portal vein (n = 5) and outflow from an isolated segment of inferior vena cava. Most patients had advanced tumor burden with a mean percentage of hepatic replacement of 25% (range, 10-75%) and a median number of metastatic nodules of 25 (range, 5 to >50). Complete vascular isolation was confirmed in all patients using a continuous intraoperative leak monitoring technique with 131I radiolabeled albumin. There was one treatment mortality (5%). The overall response rate in 21 patients was 62% including 2 radiographic complete responses (9.5%) and 11 partial responses (52%). The overall median duration of response was 9 months (range, 5-50) and was significantly longer in those treated with TNF than without (14 versus 6 months, respectively; P = 0.04). Overall median survival in 22 patients was 11 months. These data indicate that a single 60-min IHP can result in significant regression of advanced hepatic metastases from ocular melanoma. TNF appears to significantly prolong the duration of response.