Sequential transcatheter arterial chemoembolization and portal vein embolization before right hemihepatectomy in patients with hepatocellular carcinoma.

BACKGROUND: Recent studies showed that sequential selective transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE) provided better future liver remnant (FLR) regeneration rate and disease-free survival following surgery compared with PVE alone. The present study aimed to clarify whether preoperative sequential TACE and PVE before right hemihepatectomy can reduce postoperative hepatocellular carcinoma (HCC) recurrence and improve long-term disease-free and overall survival. METHODS: Recurrence and survival outcomes were retrospectively evaluated in 205 patients with HCC who underwent right hemihepatectomy by a single surgeon from November 1993 to November 2017. Patients were divided into four groups according to the procedure performed before the surgery: sequential TACE and PVE (TACE-PVE), PVE-only, TACE-only, or naïve control groups. The baseline patient and tumor characteristics, postoperative outcomes, recurrence-free survival and overall survival were analyzed. RESULTS: Baseline patient and tumor characteristics upon diagnosis were similar in all four groups, while sequential TACE and PVE were well tolerated. The TACE-PVE group had a higher mean increase in percentage FLR volume compared with that of the PVE-only group (17.46% ± 6.63% vs. 12.14% ± 5.93%; P = 0.001). The TACE-PVE group had significantly better overall and disease-free survival rates compared with the other groups (both P < 0.001). CONCLUSIONS: Sequential TACE and PVE prior to surgery can be an effective therapeutic strategy for patients with HCC scheduled for major hepatic resection. The active application of preoperative sequential TACE and PVE for HCC would allow more patients with marginal FLR volume to become candidates for major hepatic resection by promoting compensatory FLR hypertrophy without the deterioration of basal hepatic functional reserve or tumor progression.

Treatment of hepatocellular carcinoma with portal venous tumor thrombosis: A comprehensive review.

The natural history of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal (approximately 2-4 mo), and PVTT is reportedly found in 10%-40% of HCC patients at diagnosis. According to the Barcelona Clinic Liver Cancer (BCLC) Staging System (which is the most widely adopted HCC management guideline), sorafenib is the standard of care for advanced HCC (i.e., BCLC stage C) and the presence of PVTT is included in this category. However, sorafenib treatment only marginally prolongs patient survival and, notably, its therapeutic efficacy is reduced in patients with PVTT. In this context, there have been diverse efforts to develop alternatives to current standard systemic chemotherapies or combination treatment options. To date, many studies on transarterial chemoembolization, 3-dimensional conformal radiotherapy, hepatic arterial chemotherapy, and transarterial radioembolization report better overall survival than sorafenib therapy alone, but their outcomes need to be verified in future prospective, randomized controlled studies in order to be incorporated into current treatment guidelines. Additionally, combination strategies have been applied to treat HCC patients with PVTT, with the hope that the possible synergistic actions among different treatment modalities would provide promising results. This narrative review describes the current status of the management options for HCC with PVTT, with a focus on overall survival.

Transarterial chemoembolization vs. radiofrequency ablation for the treatment of single hepatocellular carcinoma 2 cm or smaller.

OBJECTIVES: To compare the effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for treating small (≤2 cm) hepatocellular carcinomas (HCCs). METHODS: This retrospective study consisted of 287 patients (mean age, 57.1 years; age range, 29-84 years; 221 men, 66 women; 73.5% with HBV; 100% with liver cirrhosis) with Barcelona Clinic Liver Cancer very early-stage HCC (≤2 cm single HCC) who were initially treated with TACE (n=122) or RFA (n=165). The primary study end point was overall patient survival. Secondary study end points were time to progression and tumor response. RESULTS: The RFA and TACE groups were well balanced in terms of baseline variables. The two groups did not differ significantly in overall survival (P=0.079) or major complication (P>0.999) rates. The respective cumulative survival rates at 1, 3, 5, and 8 years were 97.6, 86.7, 74.5, and 60.0% for RFA and 93.4, 75.4, 63.1, and 51.1% for TACE. Their objective tumor regression (complete or partial response) rates were 100% (165/165) and 95.9% (117/122), respectively (P=0.013). The median times to progression for RFA and TACE were 27.0±3.8 (95% confidence intervals (CIs): 19.6-34.4) and 18.0±2.9 (95% CIs: 12.2-23.8) months, respectively. RFA yielded a significantly longer time to progression (P=0.034). CONCLUSIONS: TACE may be a viable alternative treatment for ≤2 cm HCCs when RFA is not feasible.

Predisposing factors of hepatocellular carcinoma recurrence following complete remission in response to transarterial chemoembolization.

BACKGROUND AND AIM: The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE). METHODS: A total of 220 consecutive HCC patients who had achieved CR by TACE were followed for a median 72 months. CR was defined as complete lipiodol uptake based on the results of lipiodol-computed tomography 4 weeks after TACE and no additional tumor staining on the follow-up angiography. Recurrence patterns were classified as local recurrence and secondary tumor, respectively, in relation to the location of recurrence; early and late recurrence were classified in relation to recurrence time. RESULTS: Recurrence of HCC was observed in 169 patients (77 %), of whom 91 (54 %) had local recurrences, 61 (36 %) had secondary tumor, and 17 (10 %) had both. There were 45 (27 %) early and 124 (73 %) late recurrences. Local recurrence developed more frequently in patients with early recurrence than in those with late recurrence (62 vs. 51 %, respectively), while secondary tumor was detected more commonly in patients with late recurrence than in those with early recurrence (39 vs. 29 %, respectively; P < 0.001). In multivariate analyses, multinodularity [hazard ratio (HR) 2.351, P = 0.023] and a persistently high serum alpha-fetoprotein level following CR (HR 3.173, P < 0.001) were significant predictors of early recurrence. Older age (≥ 60 years; HR 1.531, P = 0.043), advanced Child-Pugh class (HR 1.983, P = 0.002), and the association with cirrhosis (HR 1.756, P = 0.028) were predictors of late recurrence following CR. CONCLUSIONS: Early recurrences following CR by TACE may be due mainly to undetectable remaining tumors, whereas late recurrences may be caused by newly appearing tumors in patients with a background of advanced cirrhotic liver.

Transarterial chemoembolization for hepatocellular carcinoma after transjugular intrahepatic portosystemic shunt.

BACKGROUND: The decreased portal blood flow and the potential decrease in arterial nutrient hepatic blood flow after creation of a transjugular intrahepatic portosystemic shunt (TIPS) makes the treatment of hepatocellular carcinoma (HCC) challenging. PURPOSE: To evaluate the safety and efficacy of transarterial chemoembolization (TACE) after TIPS in patients with HCC. MATERIAL AND METHODS: From 1998 to 2009, 20 patients underwent selective (segmental or subsegmental) TACE for HCC after TIPS. Among 20 patients, seven patients had undergone one to three sessions of TACE for HCC before TIPS creation. TACE was performed using a mixture of iodized oil and cisplatin, and absorbable gelatin sponge particles. Tumor response, complications, and patient survival were evaluated after TACE. RESULTS: After TACE, 14 of the 20 (70%) patients showed a tumor response, with only one (5%) experiencing a TACE-related major complication, spontaneous bacterial peritonitis. None of the patients who underwent TACE after TIPS died within 30 days. During the follow-up period (range 2.2-107 months; mean 32.6 months), 18 patients died and two remained alive. The median survival period after TACE was 23 months. Multivariate Cox regression analysis showed that tumor stage was the only independent prognostic factor for patient survival (P = 0.049). CONCLUSION: Selective TACE may be safe and effective for the palliative treatment of HCC in patients with TIPS. Late tumor stage ( ≥III) was poor prognostic factor for determining the patient survival period after post-TIPS TACE.

Transcatheter renal artery embolization with N-butyl cyanoacrylate.

BACKGROUND: Despite its long history, the application of N-butyl cyanoacrylate (NBCA) has been limited compared to other materials such as particulate agents and coils. This possibly owes to a widespread misconception that NBCA is difficult to handle and carries a high risk of complications due to its liquid nature and rapid polymerization time. However, recent reports have shown that, with knowledge and experience, NBCA is safe and effective to use in visceral arteries. PURPOSE: To review the outcome of transcatheter embolization of the renal artery using NBCA for varied etiologies in the kidney. MATERIAL AND METHODS: Fourteen patients with varied etiologies in the kidney underwent renal artery embolization using NBCA as the sole embolic agent (64%) or in combination with an additional embolic material (36%). A review of medical charts and images were performed to gather information regarding underlying etiologies, clinical presentation, and outcome of embolization. RESULTS: Technical success was achieved in all patients (100%) while clinical success was achieved in 12 (85.7%). One failed case was managed by repeat embolization using microcoils, while the other underwent partial nephrectomy after failed reattempt at embolization. Three patients with recurrent bleeding after previously having undergone embolization using microcoils or gelatin sponge particles were successfully managed the second time using NBCA. NBCA embolization was also effective in three patients with hemostatic abnormality. Complications attributable to NBCA embolization were renal atrophy in one patient and microcatheter tip fracture in another. CONCLUSION: The application of NBCA for transcatheter embolization of varied etiologies involving the renal artery is feasible and safe in the hands of an experienced interventional radiologist. It offers immediate and effective occlusion of the pathologic vessel and, while it can be used exclusively on its own, it can also be used to complement other embolic materials.

Clinical outcome of 251 patients with extrahepatic metastasis at initial diagnosis of hepatocellular carcinoma: does transarterial chemoembolization improve survival in these patients?

BACKGROUND AND AIMS: The therapeutic efficacy of transarterial chemoembolization (TACE) has not been evaluated in hepatocellular carcinoma (HCC) patients with extrahepatic metastasis. We investigated the efficacy of TACE with/without systemic chemotherapy (s-chemo) in these patients. METHODS: We performed a survival analysis of consecutive HCC patients with extrahepatic metastasis, diagnosed at initial presentation according to treatment modality after stratification, using the Child-Pugh classification and intrahepatic HCC T stage, retrospectively. RESULTS: Between 2005 and 2007, 251 patients were newly diagnosed with HCC involving extrahepatic metastasis at our institution. Among those, 226 were classified as Child-Pugh A-B and the other 25, Child-Pugh C. Within the Child-Pugh A-B group, repeated TACE or transarterial chemoinfusion (TACI) was performed with/without s-chemo in 171 patients. Eight of 226 received s-chemo alone, and 47, conservative management (CM) alone. The median survival time of patients treated with TACE/TACI with s-chemo, TACE/TACI alone, and CM was 10, 5, and 2.9 months in patients classified as Child-Pugh A and T3-stage HCC (TACE/TACI with s-chemo vs CM, P=0.0354; TACE/TACI alone vs CM, P=0.0553) and 7.1, 2.6, and 1.6 months in Child-Pugh B and T3-stage patients, respectively (TACE/TACI with s-chemo vs CM, P=0.0097; TACE/TACI alone vs CM, P<0.0001). Individual treatment with TACE/TACI or sorafenib showed independent prognostic significance in the multivariate analysis. CONCLUSION: Repeated TACE could show significant survival benefits in metastatic HCC patients with conserved liver function and intrahepatic HCC T3 stage. The survival data of our study could be used as a historical control for TACE monotherapy in future clinical trials evaluating combination treatments containing TACE in these patients.

Nonresectable combined hepatocellular carcinoma and cholangiocarcinoma: analysis of the response and prognostic factors after transcatheter arterial chemoembolization.

PURPOSE: To evaluate the clinical effectiveness of transcatheter arterial chemoembolization (TACE) performed in patients with nonresectable combined hepatocellular carcinoma (HCC) and cholangiocarcinoma and analyze the prognostic factors of patient survival after TACE. MATERIALS AND METHODS: Each patient provided informed consent for TACE. The institutional review board approved the current study and waived the requirement for patient consent for this retrospective review. From 1997 to 2009, 50 patients underwent TACE for nonresectable combined HCC-cholangiocarcinoma. Tumor response was evaluated on the basis of findings on computed tomographic (CT) scans obtained a mean of 30.7 days after TACE. The survival rate and the prognostic factors of patient survival were evaluated. RESULTS: After TACE, 35 (70%) of the 50 patients were classified as responders--having either a partial response or stable disease with successful (>50%) tumor necrosis--and 15 (30%) were classified as nonresponders. Tumor response was significantly related to tumor vascularity: One (10%) of the 10 patients with hypovascular tumors and 34 (85%) of the 40 patients with hypervascular tumors were responders (P < .001). The median patient survival period was 12.3 months. Results of multivariable Cox regression analyses confirmed that tumor size (hazard ratio [HR], 2.49; P = .028), tumor vascularity (HR, 4.19; P = .001), Child-Pugh class (HR, 4.3; P = .001), and portal vein invasion (HR, 6.45; P < .001) were the independent factors associated with patient survival duration after TACE. CONCLUSION: TACE is safe and may be effective for prolonging the survival of patients with nonresectable combined HCC-cholangiocarcinoma, as compared with the historically reported survivals of these patients. Tumor vascularity is highly associated with tumor response. The patient survival period after TACE for combined HCC-cholangiocarcinoma is significantly dependent on tumor size, tumor vascularity, Child-Pugh class, and presence or absence of portal vein invasion.

Transcatheter arterial chemoembolization for hepatocellular carcinoma after attempted portal vein embolization in 25 patients.

OBJECTIVE: Portal vein embolization (PVE) has been widely used to facilitate major liver resection; however, curative surgery even after PVE may not be possible mainly because of inadequate hypertrophy of remnant liver or disease progression. For these patients, transcatheter arterial chemoembolization (TACE) is the next therapeutic option. We evaluated the safety and efficacy of TACE after PVE in 25 patients with hepatocellular carcinoma (HCC). CONCLUSION: TACE using a single chemotherapeutic agent can be performed safely and effectively in HCC patients who previously underwent PVE. TACE after PVE allowed two of the patients to be downstaged so they could undergo surgical resection.

Tumor response to transcatheter arterial chemoembolization in recurrent hepatocellular carcinoma after living donor liver transplantation.

OBJECTIVE: To evaluate the tumor response and patient survival rate following transcatheter arterial chemoembolization (TACE) in recurrent hepatocellular carcinoma (r-HCC) after living donor liver transplantation (LDLT). MATERIALS AND METHODS: Twenty-eight patients with r-HCC underwent one or more cycles of TACE after LDLT (mean, 2.5 cycles). After a mixture of iodized oil and anti-cancer drugs was injected via the arteries feeding the tumors, these vessels were embolized with a gelatin sponge. Tumor response was determined by follow-up CT imaging on all patients four weeks after each TACE procedure. Patient survival was calculated using the Kaplan-Meier survival curve. RESULTS: After TACE, targeted tumor reduced in size by 25% or more in 19 of the 28 study patients (67.9%). However, intrahepatic recurrence or extrahepatic metastasis occurred in 21 of the 28 patients (75.0%) during the 3-month follow-up period and in 26 of the 28 patients (92.9%) during the 6-month period following TACE. Extrahepatic metastasis was noted in 18 of the 28 patients (64.3%). The 1-, 3- and 5-year survival rates following TACE were 47.9, 6.0 and 0%, respectively, with a mean survival of nine months in all patients. There were no significant complications related to TACE. CONCLUSION: TACE produces an effective tumor response for targeted r-HCC after LDLT. However, the survival rate of patients with r-HCC after LDLT is poor due to extrahepatic metastasis and intrahepatic recurrence.