Treatment Of Primary Hepatocellular Carcinoma Research Articles

Combined Transarterial Chemoembolization (TACE) and Stereotactic Body Radiation Therapy (SBRT) for Management of Primary Hepatocellular Carcinoma (HCC)

Surgical resection and orthotropic liver transplant (OLT) have been established as curative options for Hepatocellular Carcinoma (HCC). However, various factors delay surgical therapy and there is often a long waiting time for donor liver. Alternative, as well as temporizing, therapeutic options include transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT). We evaluated the efficacy and safety of combined TACE followed by SBRT for the treatment of primary HCC. From August 2011 to October 2012, 25 patients received sequential TACE followed by SBRT for HCC lesions at our institution: 11 Child-Turcotte-Pugh (CTP) Class A and 14 CTP Class B. 24 patients had HCC and 1 had mixed histology of HCC with cholangiocarcinoma. Twenty-three patients had a single lesion treated and 2 patients had 2 lesions treated. Seventeen patients had Hepatitis C and 4 had Hepatitis B. The median time from TACE to SBRT was 5 days (range, 2-49 days). The median dose, dose per fraction, and number of fractions was 4000 cGy (range, 1200-4000 cGy), 800 (range, 600-800 cGy), and 5 (range, 2-5 cGy), respectively. All patients were treated with cone beam CT (CBCT) imaging, with treatment delivered every other day. Abdominal compression was utilized in 21 patients and an ITV was generated via 4DCT for 23 patients. The mean GTV and ITV volumes were 32.4 cc (range, 0.5-104.2 cc) and 196.8 cc (range, 2.5-196.8 cc). Treatment response was scored according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Regional failure was defined as intrahepatic progression of disease outside of the treated lesion. Local control (LC), disease free survival (DFS), and time to progression (TTP) were calculated according to the method of Kaplan-Meier. The mean follow-up time was 6.9 months (range, 1-12.7 months). Twenty-five (100%) patients experienced local control over this time period. The 8 month DFS was 71%, with 4 regional and 2 distant failures occurring in 4 patients. Median TTP was 7.8 months. 17 (68%) patients experienced complete response of tumor to treatment; 4 (16%) patients had a partial response and 1 (4%) had stable disease. The mean time to radiographic CR was 4.4 months (range, 1-9 months). Two patients had treatment truncated unrelated to treatment toxicity and three candidates went on to transplant. Two patients experienced grade 1 nausea one month post treatment and three experienced abdominal discomfort for which they were prescribed analgesic medicine. Two CTP Class B patients with pre-existing ascites experienced an increase in ascites post-treatment. Combined TACE followed by SBRT is a feasible therapeutic option which is well tolerated and can provide outstanding local control for primary HCC lesions. Further follow-up is needed to better characterize treatment outcome.

Surgical resection versus radiofrequency ablation in the treatment of primary hepatocellular carcinoma with type I portal vein tumor thrombus

Objective To compare the results of surgical resection with radloirequency ablation in the treatment of primary hepatocellular carcinoma with type I portal vein tumor thrombus. Methods The clinical data of 30 patients with primary hepatocellular carcinoma with type Ⅰ portal vein tumor thrombus treated between January 2006 and December 2009 were analyzed retrospectively. Patients were divided into two groups according to the treatment. Result The treatments were successfully carried out in the surgical resection group （n= 15） and the radiofrequency ablation group （n = 15）. There was no perioperative death. Both surgical resection and radiofrequency ablation improved the overall survival and recurrence-free survival. The survival outcome of radiofrequency ablation was similar to surgical resection. Conclusion Both surgical resection and radiofrequency ablation were safe and effective for patients with primary hepatocellular carcinoma with type I portal vein tumor thrombus and improved the overall survival and recurrence-free survival. Key words: Surgery ; tumor thrombus Radiofrequency ablation~ Hepatocellular carcinoma Ⅰ Portal vein

Transarterial Chemoembolization Treatment: Association between Multiple Treatments, Cumulative Expenditures, and Survival

To examine cumulative survival and Medicaid-paid expenses associated with multiple courses of transarterial chemoembolization (TACE) as primary treatment for hepatocellular carcinoma (HCC). Medicare enrollees diagnosed with primary HCC from 2000 to 2007, ever treated with TACE, but not transplant/resection, followed through 2009 by using the Surveillance, Epidemiology and End-Results Program and linked Medicare databases. Cumulative all-cause/HCC-related survival was estimated by using multivariate Cox proportional hazards models stratified by the total number of TACE treatments. Multivariate weighted Cox regressions estimated the average risk of mortality faced with nonproportional hazards. Lin's inverse probability-weighted least squares regression method estimated cumulative Medicare expenditures adjusted for censoring and covariates. Of 1228 patients, 34% were stage 1, 16% stage 2, 19% stage 3, 6% stage 4, and 26% unstaged. About 44% were aged 65 to 75 years, 69% were men, and 72% were Caucasian. Over half (57%) of the patients received one course, 24% two, 11% three, and 8% four courses of TACE. One-course patients incurred an average $74,788 (95% confidence interval [CI] $71,890-$77,686), two-course patients $101,126 (95% CI $94,395-$107,856), three-course patients $111,776 (95% CI $101,931-$121,621), and four-plus-course patients $148,878 (95% CI $136,346-$161,409). One-course patients lived (all-cause) an average 1.86 (95% CI 1.82-1.90), two-course patients 2.09 (95% CI 2.05-2.13), three-course patients 2.81 (95% CI 2.66-2.97), and four-plus-course patients 3.06 (95% CI 2.95-3.18) years after diagnosis. Average risk of all-cause mortality was not significantly different between one/two courses or three/four-plus courses. Cumulative Medicare expenditures nearly doubled from one-course to four-plus-course patients. On average, four-plus-course patients lived over one more year than did one-course patients. Physician/patient decisions should be balanced with consideration of efficient use of limited resources, but payer's intervention in physician discretion may not be important in this setting.

Significance of transcatheter arterial chemoembolization combined with sorafenib for the treatment of primary hepatocellular carcinoma

Transcatheter arterial chemoembolization (TACE) was the preferred method of non-operation treatment for hepatocellular carcinoma (HCC).Radical resection of HCC remains difficult,extrahepatic metastasis was not easy to deal with,and repeated treatment aggravated the liver injury,so the long-term efficacy was poor.Sorafenib could control tumor angiogenesis and block the proliferation of tumor cells.A male patient with primary HCC and in the stage Ⅱb according to the Chinese clinical liver cancer staging system was treated by TACE combined with sorafenib and antiviral treatment in Henan Cancer Hospital.After the treatment,the intrahepatic lesions were inactive,and the pulmonary metastasis was partially relieved.The patient was followed up till May 2012,and the survival time was 39 months.The hepatic function was normal,and the hepatitis B virus (HBV) replication was negative.No intervention treatmentrelated complications were detected,and the KPS score was 100. Key words: Liver neoplasms; Transcatheter arterial chemoembolization ; Sorafenib ; Interventional radiology

Radiotherapy with volumetric modulated arc therapy for hepatocellular carcinoma patients ineligible for surgery or ablative treatments

The aim of this article is to report the dosimetric and clinical findings in the treatment of primary hepatocellular carcinoma (HCC) with volumetric modulated arc therapy (VMAT, RapidArc). A total of 138patients were investigated. Dose prescription ranged from 45-66Gy. Most patients (88.4 %) presented AJCC stage III or IV and 83 % were N0-M0. All were classified as Barcelona Clinic Liver Cancer (BCLC) stage A-C. All patients were treated using 10MV photons with single or multiple, coplanar or non-coplanar arcs, and cone-down technique in case of early response of tumors. The patients' median age was 66years (range 27-87years), 83 % were treated with 60Gy (12 % at 45Gy, 6 % at 66Gy), 62 % with cone-down, 98 % with multiple arcs. The mean initial planning target volume (PTV) was 777 ± 632cm(3); the mean final PTV (after the cone-down) was 583 ± 548cm(3). High target coverage was achieved. The final PTV was V98% > 98 %. Kidneys received on average 5 and 8Gy (left and right), while the maximum dose to the spinal cord was 22Gy; mean doses to esophagus and stomach were 23Gy and 15Gy, respectively. The average volume of healthy liver receiving more than 30Gy was 294 ± 145cm(3). Overall survival at 12months was 45 %; median survival was 10.3months (95 % confidence interval 7.2-13.3months). Actuarial local control at 6months was 95 % and 93.7 % at 12months. The median follow-up was 9months and a maximum of 28months. This study showed from the dosimetric point of view the feasibility and technical appropriateness of RapidArc for the treatment of HCC. Clinical results were positive and might suggest, with appropriate care, to consider RapidArc as an additional therapeutic opportunity for these patients.

P-0090 Stereotactic Body Radiation Therapy with Real-Time Tracking for Hepatocellular Carcinoma

IntroductionStereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) is a recent addition to the already available treatment options. In order to be able to deliver ablative doses, a tracking of the lesion is required. The CyberKnife is a SBRT system that allows for real-time tracking of the tumor. The purpose of this study was to evaluate the safety and efficacy of this system for the treatment of primary hepatocellular carcinoma. MethodsFrom July 2007 to November 2011, 75 patients with 96 liver-confined HCC were treated with SBRT at the Oscar Lambret Comprehensive Cancer Center. Three to four gold seeds were implanted inside the patients' liver before treatment and were used as markers to follow the movement of the lesion due to respiration. Treatment response was scored according to Response Evaluation Criteria in Solid Tumors v1.1. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Local control and overall survival were calculated according to the method of Kaplan and Meier. ResultsThere were 67 patients with Child-Turcotte-Pugh (CTP) Class A and 8 patients with CTP Class B. Treatment was administered in three sessions. A total dose of 40 to 45Gy at the 80% isodose was delivered with a median number of 146 beams. The average follow-up was 10 months (min : 3 – max : 44). The local control rate was 89.8% at 1 and 2 years. Overall survival was 78.5% and 50.4% at 1 and 2 years. Treatment toxicity was low. The most common toxicities were pain and asthenia. 1 patient had a gastric ulcer. No grade 3 toxicity was observed. ConclusionThis treatment, while minimally invasive, presents tumoral local control and overall survival rates comparable to other treatments. The toxicity was low for our patients. It could be considered for patients not amenable to surgery or chemoembolization. A randomized trial comparing SBRT to the other available treatments should be conducted to validate this results.

Survival advantage of primary liver transplantation for hepatocellular carcinoma within the up-to-7 criteria with microvascular invasion

PurposeMicrovascular invasion of hepatocellular carcinoma (HCC) is considered a poor prognostic factor of liver resection (LR) and liver transplantation (LT), but its significance for lesions within the up-to-7 criteria is unclear. This study investigated the survival benefit of primary LT against LR for HCC with microvascular invasion and within the up-to-7 criteria.MethodsAdult patients who underwent LR or LT as the primary treatment for HCC were included for study. Patients with prior local ablation, neoadjuvant systemic chemotherapy, targeted therapy, positive resection margin, or metastatic spread were excluded.ResultsThere were 471 LR patients and 95 LT recipients (70 with living donor, 25 with deceased donor). Seventy-seven (81.1%) LT recipients had HCC within the up-to-7 criteria. Twenty-five (26.3%) LT recipients had HCC with either macrovascular (n = 4) or microvascular (n = 21) invasion. The 5-year survival rate was 85.7% for LT recipients with HCC within the up-to-7 criteria, unaffected by the presence or absence of vascular invasion (88.2 vs. 85.1%). The rate was comparable with that of LR patients with HCC without vascular invasion (81.2%, p 0.227), but far superior to that of LR patients with lesions with vascular invasion (50.0%, p < 0.0001). Overall survivals were compromised by multiple tumors [odds ratio (OR) 1.902, confidence interval (CI) 1.374–2.633, p = 0.0001], vascular invasion (OR 2.678, CI 1.952–3.674, p < 0.0001), blood transfusion (OR 2.046, CI 1.337–3.131, p = 0.001), and being beyond the up-to-7 criteria (OR 1.457, CI 1.041–2.037, p = 0.028). LT was a favorable factor for survival (OR 0.243, CI 0.130–0.454, p < 0.0001).ConclusionPrimary LT for HCC with microvascular invasion and within the up-to-7 criteria doubled the chance of cure as compared with LR.

Surgical Approach for Extrahepatic Metastasis of HCC in the Abdominal Cavity

Despite recent development of therapeutic strategies for intrahepatic lesions, standard guidelines for treatment of extrahepatic metastases of hepatocellular carcinoma have not been established. Surgical resection for intra-abdominal extrahepatic metastases of hepatocellular carcinoma was performed on 10 patients at our institution between 1992 and 2008. We retrospectively examined the clinicopathologic features and significance of a surgical approach in these patients. Nine of the 10 patients received treatment for primary hepatocellular carcinoma before surgery for intra-abdominal extrahepatic metastasis. A simultaneous intrahepatic lesion was detected in half of the patients when the extrahepatic metastasis was resected. Extrahepatic recurrent organs included adrenal glands, lymph nodes, abdominal wall, stomach and diaphragm. The mean survival period after resection was 36.1 months. Two patients are still alive without further recurrence. One patient died of retroperitoneal recurrence and 7 died of intrahepatic recurrence or liver failure after resection. With careful case selection, considering that not all extrahepatic metastases suggest systemic spread of hepatocellular carcinoma, surgical treatment for metastatic lesions in the abdominal cavity can provide a relatively good prognosis.

Highly sensitive AFP‐L3% assay is useful for predicting recurrence of hepatocellular carcinoma after curative treatment pre‐ and postoperatively

The micro-total analysis system (µTAS), a fully automated immunoassay system using microchip capillary electrophoresis, is highly sensitive and able to quickly assay the AFP-L3%. The clinical usefulness of this system was studied. We retrospectively enrolled 250 patients who underwent curative treatment for primary hepatocellular carcinoma (HCC) (93 patients underwent hepatic resection and 157, radiofrequency ablation [RFA]). The sensitivity for µTAS AFP-L3% was 40.3% at the cutoff value of 5% in a range of AFP less than 20 ng/mL where the conventional method was unable to determine AFP-L3%. The sensitivity for AFP-L3% remained high even at stage I and at tumor size less than 2 cm (42.5% and 46.0%, respectively). Recurrence rate of patients with AFP-L3% greater than 5% was significantly higher than that of patients with less than 5% (P = 0.001). Furthermore, in resected patients, the postoperative AFP-L3% remained elevated with value greater than 5% was related to HCC recurrence (P = 0.001). Multivariate analysis revealed that multiple tumors (P = 0.004), preoperative AFP-L3% greater than 5% (P = 0.003), albumin less than 3.5 g/dL (P = 0.008), and RFA (P = 0.003) were significant prognostic factors of recurrence. The µTAS was found to be a highly sensitive assay for AFP-L3% in patients with curative treatment of HCC. A cutoff value of 5% was useful for predicting recurrence after the curative treatment and detecting small tumors and early stage HCC. Additionally, postoperative AFP-L3% was found to be a prognostic factor of HCC recurrence.

Radiofrequency ablation versus surgical resection as primary treatment of hepatocellular carcinoma meeting the Milan criteria: A systematic review

Surgery is the standard treatment option for hepatocellular carcinoma (HCC) meeting the Milan criteria, defined as single HCC ≤ 5 cm in maximum diameter or up to three nodules ≤ 3 cm. However, favorable survival outcomes have also been reported for these HCCs following radiofrequency ablation (RFA). We performed a systematic review to compare the results of hepatic resection and percutaneous RFA as a primary treatment option of HCC meeting the Milan criteria. Studies were identified by searching MEDLINE on PubMed, the Cochrane Library database and CANCERLIT using appropriate key words. In all six identified observational studies, there were no statistically significant differences in overall survival rates between the two treatment modalities. The results of two randomized trials are controversial, while the power of these randomized trials is too limited to reach a reliable conclusion. In practice, the choice of treatment between surgery and RFA largely depends on the relationship between the local recurrence and perioperative mortality rates of HCC patients. Following RFA, local recurrence rates are low when a minimal safety margin ≥ 4-5 mm is achieved. A previous simulation study of overall survival for very early stage HCC, defined as an asymptomatic solitary small HCC ≤ 2 cm, showed that primary RFA with a 9% local recurrence rate is comparable to surgical resection with a 3% operative mortality rate. Acquisition of a sufficient safety margin seems to be a critical factor before recommending wider application of RFA as primary treatment for HCCs that meet the Milan criteria.

Stereotactic Body Radiotherapy for Primary Hepatocellular Carcinoma

To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of primary hepatocellular carcinoma (HCC). From 2005 to 2009, 60 patients with liver-confined HCC were treated with SBRT at the Indiana University Simon Cancer Center: 36 Child-Turcotte-Pugh (CTP) Class A and 24 CTP Class B. The median number of fractions, dose per fraction, and total dose, was 3, 14 Gy, and 44 Gy, respectively, for those with CTP Class A cirrhosis and 5, 8 Gy, and 40 Gy, respectively, for those with CTP Class B. Treatment was delivered via 6 to 12 beams and in nearly all cases was prescribed to the 80% isodose line. The records of all patients were reviewed, and treatment response was scored according to Response Evaluation Criteria in Solid Tumors v1.1. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Local control (LC), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were calculated according to the method of Kaplan and Meier. The median follow-up time was 27 months, and the median tumor diameter was 3.2 cm. The 2-year LC, PFS, and OS were 90%, 48%, and 67%, respectively, with median TTP of 47.8 months. Subsequently, 23 patients underwent transplant, with a median time to transplant of 7 months. There were no ≥Grade 3 nonhematologic toxicities. Thirteen percent of patients experienced an increase in hematologic/hepatic dysfunction greater than 1 grade, and 20% experienced progression in CTP class within 3 months of treatment. SBRT is a safe, effective, noninvasive option for patients with HCC ≤6 cm. As such, SBRT should be considered when bridging to transplant or as definitive therapy for those ineligible for transplant.

Tract Seeding Following Radiofrequency Ablation for Hepatocellular Carcinoma: Prevention, Detection, and Management

Radiofrequency ablation (RFA) has become an important tool in the armamentarium of interventional oncology, particularly in the treatment of primary hepatocellular carcinoma and metastatic tumors. This procedure has proven to be an effective adjunct in treating hepatic tumors as a bridge to liver transplantation, and has a low complication profile. Although adverse events are rare and usually minor, a notable negative outcome is dissemination and implantation of viable tumor cells into the route of applicator entry, or tract seeding. Counter to the goal of treating a patient's cancer, this results in metastatic disease. In this report, the authors present 2 cases of tract seeding after RFA, methods of detection, and means of reducing the incidence of this relatively rare, but significant, complication.

Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells.

There is increasing evidence that the physical environment is a critical mediator of tumor behavior. Hepatocellular carcinoma (HCC) develops within an altered biomechanical environment, and increasing matrix stiffness is a strong predictor of HCC development. The aim of this study was to establish whether changes in matrix stiffness, which are characteristic of inflammation and fibrosis, regulate HCC cell proliferation and chemotherapeutic response. Using an in vitro system of "mechanically tunable" matrix-coated polyacrylamide gels, matrix stiffness was modeled across a pathophysiologically relevant range, corresponding to values encountered in normal and fibrotic livers. Increasing matrix stiffness was found to promote HCC cell proliferation. The proliferative index (assessed by Ki67 staining) of Huh7 and HepG2 cells was 2.7-fold and 12.2-fold higher, respectively, when the cells were cultured on stiff (12 kPa) versus soft (1 kPa) supports. This was associated with stiffness-dependent regulation of basal and hepatocyte growth factor-stimulated mitogenic signaling through extracellular signal-regulated kinase, protein kinase B (PKB/Akt), and signal transducer and activator of transcription 3. β1-Integrin and focal adhesion kinase were found to modulate stiffness-dependent HCC cell proliferation. Following treatment with cisplatin, we observed reduced apoptosis in HCC cells cultured on stiff versus soft (physiological) supports. Interestingly, however, surviving cells from soft supports had significantly higher clonogenic capacity than surviving cells from a stiff microenvironment. This was associated with enhanced expression of cancer stem cell markers, including clusters of differentiation 44 (CD44), CD133, c-kit, cysteine-X-cysteine receptor 4, octamer-4 (CXCR4), and NANOG. Increasing matrix stiffness promotes proliferation and chemotherapeutic resistance, whereas a soft environment induces reversible cellular dormancy and stem cell characteristics in HCC. This has implications for both the treatment of primary HCC and the prevention of tumor outgrowth from disseminated tumor cells. (HEPATOLOGY 2011;).

Treatment of primary hepatocellular carcinoma

Primary hepatocellular cancer is the fifth most common solid tumor worldwide. Its incidence is the highest in the Third World, however, a risen incidence has been observed recently also in developed countries, due to increasing migration. In Asia and Africa the main etiological factor for HCC is chronic HBV infection, whereas in the Western world HCV etiology predominates. Additional increase in HCC incidence is expected as a consequence of climate change, since risk of aflatoxin contamination in agricultural products increases with hot and dry growing conditions. Aflatoxins are the most potent hepatocarcinogens in nature; therefore minimization of aflatoxin exposition will be a main task of food security in the future. The majority of HCC patients are diagnosed in advanced stages, and treatment possibilities are limited for this patient population. Follow-up of risk populations by means of tumor surveillance is therefore essential. Experience with systemic chemotherapy has been disappointing with low response rates and high toxicity. Recently, novel treatment options have emerged, including the use of specific targeted agents, blockers of signaling pathways involved in hepatocarcinogenesis. Sorafenib, an oral multikinase-inhibitor is the first systemic agent to demonstrate survival benefit in advanced hepatocellular cancer. Several new, promising therapeutic options are being tested in clinical trials.

The efficacy and safety of transcatheter arterial chemoembolization combined with Endostar for primary hepatocellar carcinoma

Objective:To investigate the efficacy and safety of combined therapy of transcatheter arterial chemoembolization with Endostar for primary hepatocellular carcinoma.Methods:Fifty patients with hepatocellar carcinoma were given the combined therapy of transcatheter arterial chemoembolization with Endostar.The adverse reaction and short-term efficacy were evaluated after the combined therapy to evaluate the safety and efficacy of the combined therapy.Results:After the 50 patients with hepatocellar carcinoma received the combined therapy of transcatheter arterial chemoembolization with Endostar,the mainly observed adverse effects were Ⅰ to Ⅱ degree neutropenia and elevation in hepatic enzymes.No severe adverse effects were observed in our study.The results of short-term efficacy showed that among the 50 patients with hepatocellular carcinoma 3 had partial response(PR),40 had stable disease(SD),and 7 had progressive disease(PD).Disease control rate(DCR) was 86.0%.Conclusion:Transcatheter arterial chemoembolization combined with Endostar was safe and effective in the treatment of primary hepatocellular carcinoma.

Clinical application of virtual hepatectomy in treatment of primary hepatocellular carcinoma

Objective To assess the feasibility of virtual hepatectomy in the treatment of primary hepatocellular carcinom(PHCC).Methods From September 2007 to September 2008,three-dimensional(3D)models from MR images were constructed by 3D-Doctor software in 13 patients with PHCC scheduled for liver resection.From these 3D models,the images of vena cava,portal vein,hepatic vein and short hepatic vein were reconstructed and total liver volume,tumor volume,functional liver volume and SFLVR(ratio of functional liver volume to standard liver volume)were calculated.Results Of the 13 patients with PHCC,7 received right hemihepatectomy and 6 bisegmentectomy.The anatomic detail of liver veins and its relation to the tumor could be displayed clearly in liver 3D models.By the 3D models,tumor volume was calculated as(348±214)ml,total liver volume(676±375)ml,functional liver volume(714 ± 261)ml and SFLVR(62±19)%.Postoperative complications included pulmonary infection in 1,moderate ascites in 6 and massive ascites in 2.Conclusion Virtual hepatectomy provides an accurate picture of liver vein anatomy and its relationship with the tumor.It can predict the liver volume to be removed and functional liver volume,and may be used for the preoperative planning of safe hepatectomy. Key words: Carcinoma hepatocellular; Virtual hepatectomy; Magnetic resonance image

Insulin resistance raises the risk for recurrence of stage I hepatocellular carcinoma after curative radiofrequency ablation in hepatitis C virus‐positive patients: A prospective, case series study

Several studies have reported that insulin resistance raises the risk of primary hepatocellular carcinoma (HCC). We conducted a prospective, case series study to test the impact of insulin resistance on the recurrence after curative radiofrequency ablation (RFA) of stage I HCC in HCV-positive patients. From January 2006 to December 2007, 226 consecutive patients underwent treatment for primary HCC at our institutions, including 37 stage I cases. Among them, 33 were HCV-positive, and three, six and 24 received curative surgery, transarterial chemoembolization or RFA, respectively. In the 24 patients treated with RFA, recurrence-free survival was analyzed using the Kaplan-Meier method. The factors contributing to recurrence of HCC were subjected to univariate and multivariate analyses using the Cox proportional hazards model. Insulin resistance was estimated by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Kaplan-Meier analysis showed that the recurrence-free survival was lower in patients with higher HOMA-IR (>2.3, P = 0.0252) or with lower serum albumin level (<3.3 g/dL, P = 0.0004). In the univariate analysis, HOMA-IR (P = 0.0420) and albumin (P = 0.0036) were significantly associated with recurrence of HCC. Multivariate analysis revealed albumin (odds ratio = 0.01, 95% confidence interval = 0.0002-0.015, P = 0.0001) and HOMA-IR (odds ratio = 3.85, 95% confidence interval = 1.57-14.2, P = 0.0015) to be independent predictors for recurrence of HCC. Serum albumin level and HOMA-IR were independent risk factors for recurrence of stage I HCC after curative RFA in HCV-positive patients. Patients with these factors require closer surveillance.

Outcome of Hepatic Resection for Hepatocellular Carcinoma within the Milan Criteria in Child-Pugh Class A Patients

Purpose: Hepatic resection and liver transplantation are considered a curative treatment for hepatocellular carcinoma (HCC) within the Milan criteria. In this study, we examine the outcome of hepatic resection for HCC within the Milan criteria, and determine the effectiveness of hepatic resection as the primary treatment for HCC within the Milan criteria in Child-Pugh class A. Methods: 110 patients underwent curative surgical resection for HCC in Child-Pugh class A between August 1991 and June 2008. Fifty-six patients met Milan criteria (Group M) and the remaining 54 did not (Group N). Results: Overall survival rates at 1, 3, and 5 years were 92.6%, 72.5% and 54.6% versus 70.4%, 43.1%, and 28.7 % in Group M and Group N, respectively (P=0.0043). The corresponding disease-free survival rates were 81.5%, 69.7%, and 38.2% versus 46.0%, 32.9%, and 26.9% in Group M and Group N (P=0.0012). HCC recurred in 25 patients in Group M (44.6%) and 35 patients in Group N (64.8%)(P=0.034). Outcomes of hepatic resection in Group M were significantly better compared to Group N. Conclusion: Hepatic resection can achieve a comparable 5-year overall survival & disease-free survival to that reported for liver transplantation. Hepatic resection should be considered as the standard therapy for HCC within the Milan criteria in Child-Pugh class A patients. (J Korean Surg Soc 2010;79:49-57)

Clinical study of recombinant adenovirus-p53 combined with fractionated stereotactic radiotherapy for hepatocellular carcinoma

The purpose of our study was to evaluate the feasibility and treatment outcomes of recombinant adenovirus-p53 (rAd-p53, trademarked as Gendicine) combined with fractionated stereotactic radiotherapy (fSRT) in treatment of primary hepatocellular carcinoma (HCC). We randomly enrolled 40 patients with HCC treated by fSRT alone (fSRT group) or rAd-p53 combined with fSRT (combined group). Tumor size was 2-5.2 cm (average 3.2 cm). We prescribed 50 Gy in 10 fractions at the 50%-80% isodose line of the planning target volume for 2 weeks in two groups. The combined group was treated with two intratumoral injections of rAd-p53 on day 1 and 8 while fSRT started on day 3. Tumor response was assessed after treatment using modified WHO criteria. The follow-up period was 11-44 months (median 35 months). The overall response rate of fSRT group was 70%, with 4 patients showing complete response (20%), 10 partial response (50%) and 6 stable disease (30%). Correspondingly the overall response rate of combined group was 85%, with 7 patients showing complete response (35%), 10 partial response (50%) and 3 stable disease (15%). The 1-year survival rates of fSRT group and combined group were 70.0% and 90.0%, respectively. The 1-year disease-free survival rates of fSRT group and combined group were 65% and 85%, respectively. These treatments were well tolerated, because grade 3 or 4 toxicity was not observed. These results suggest that rAd-p53 combined with fSRT is a relatively safe and effective method for treating primary hepatocellular carcinoma compared with only fSRT. Thus, rAd-p53 combined with fractionated SRT may be preferred as a choice of local treatment for primary HCC when the patients are inoperable or when the patients refuse operation.

Advancement in comprehensive treatment of primary hepatocellular carcinoma

Advancement in comprehensive treatment of primary hepatocellular carcinoma