Local Treatments For Hepatocellular Carcinoma Research Articles

Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis

Iodine-125 (I-125) radioactive seed implantation is used for the local treatment of hepatocellular carcinoma (HCC), but the molecular mechanisms regulating its anticancer effects remain incompletely understood. In this study, we report that hsa_circ_0000647 (circSEC11A) is highly expressed after I-125 treatment in HCC cell lines and tissues and is a key regulator of I-125-induced anticancer effects. CircSEC11A acts as a competing endogenous RNA (ceRNA) to sponge miR-3529-3p, promoting the expression of zinc fingers and homeoboxes 2 (ZHX2) and enhancing I-125-induced anticancer effects. Dual-luciferase reporter assay, RNA pull-down, RNA immunoprecipitation, and fluorescence in situ hybridization were thereafter performed to verify the interaction among the molecules. Anticancer effects were detected using CCK-8, flow cytometry, TUNEL, EdU, transwell, and wound healing assays. Furthermore, ZHX2 transcriptionally inhibits GADD34, a negative regulator of endoplasmic reticulum stress (ERS), to enhance I-125- induced anticancer effects in vivo and in vitro. In conclusion, we characterized circSEC11A as a novel regulator of I-125-induced anticancer effects in HCC via miR-3529-3p/ZHX2/GADD34 axis-mediated ERS. Thus, circSEC11A may act as a potential therapeutic target for I-125 implantation in the clinic.

Comparison of Open versus Laparoscopic Approaches in Salvage Hepatectomy for Recurrent Hepatocellular Carcinoma after Radiofrequency Ablation.

Background and Objectives: Although radiofrequency ablation (RFA) is widely used as an effective local treatment for hepatocellular carcinoma (HCC), evidence on salvage hepatectomy for local recurrence after RFA is limited. This study aims to compare open and laparoscopic approaches in salvage hepatectomy for recurrent HCC after RFA. Materials and Methods: Among patients who underwent hepatectomy between January 2004 and August 2022 at a single tertiary referral center, 55 patients who underwent salvage hepatectomy for marginal recurrence after RFA were selected. An open approach was used in 23 (41.8%) patients, while 32 (58.2%) patients underwent laparoscopic surgery. Short-term and long-term outcomes were compared between the two groups. Results: Major hepatectomy was more often performed in the open group (9 [39.1%] vs. 4 [12.5%], p = 0.022). Intraoperative blood loss was also greater in the open group (450 (325-750) vs. 300 (200-600), p = 0.034). Operation time (p = 0.144) and postoperative morbidity rates (p = 0.639) were similar, and there was no postoperative mortality in either group. Postoperative hospital stay was significantly longer in the open group compared to the laparoscopy group (8 (6-11) days vs. 5 (4-7) days, p = 0.028). The 1-, 3-, and 5-year disease-free survival rates showed no difference between the two groups (44.6% vs. 62.5%, 16.5% vs. 13.5%, and 8.3% vs. 13.5%, respectively; p = 0.154). The 1-, 3-, and 5-year overall survival rates between the two groups were also similar (85.7% vs. 96.8%, 79.6% vs. 86.0%, and 79.6% vs. 79.4%, respectively; p = 0.480). Conclusions: Laparoscopic salvage hepatectomy shows oncologic outcomes comparable to the open approach with faster postoperative recovery rates. Considering that recurrence rates are high after RFA, the laparoscopic approach should be considered as a first-line option in selected patients.

Local Treatment of Hepatocellular Carcinoma with Oligometastases: A Systematic Review and Meta-Analysis

Although recent studies have shown favorable results after local treatment for oligometastases, the clinical decision of applying local treatment for oligometastatic hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aimed to investigate the benefits of local treatment for HCC oligometastases. Pubmed, Embase, Medline, and the Cochrane library were searched for studies until 1 May 2022. Clinical studies involving at least five cases of HCC oligometsatases treated with local modalities were included. The primary endpoint was overall survival (OS). The benefit of local treatment was assessed as the pooled odds ratio (OR) among comparative series, and the pooled OS percentile was calculated from all studies including patients treated with local treatment. Complications of grade ≥ 3 were assessed subjectively. A total of 10 studies involving 527 patients were included. Radiotherapy and radiofrequency ablation (RFA) were mainly performed (six and five studies) as local modalities treating oligometastases. Pooled OR of comparative series favored the use of local treatment (4.664, 95% confidence interval [CI]: 2.595–8.380, p < 0.001, I2: ~0.0%). Including all cohorts with patients who underwent local treatment, pooled rates of 1-year OS were 71.8% (95% CI: 59.0–81.9; I2 = 81.5%), and pooled 2-year OS were 43.3% (95% CI: 29.1–59.6; I2 = 85.4%). Except for temporal or pre-existing toxicities, grade ≤ 3 complications were reported less than 10% in most studies, although common toxicities include pneumothorax and hematologic deficiency after RFA and radiotherapy, respectively. Grade 5 toxicity has not yet been reported. This systematic review supports the application of local treatment for treating HCC oligometastases.

Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab.

Radiotherapy (RT) is an effective local treatment for hepatocellular carcinoma (HCC). However, whether additional RT is safe and effective in patients with advanced HCC receiving atezolizumab plus bevacizumab remains unclear. This retrospective cohort study aimed to evaluate the feasibility of additional RT in these patients. Between March and October 2021, we retrospectively analyzed seven patients with advanced HCC who received RT during treatment with atezolizumab plus bevacizumab. The median prescribed RT dose was 35 Gy (range, 33-66). Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) after RT were analyzed. The median follow-up duration after RT was 14.2 months (range, 10.0-18.6). Of the seven patients, disease progression was noted in six (85.7%), the sites of disease progression were local in two (28.6%), intrahepatic in four (57.1%), and extrahepatic in four (57.1%). The median time of FFLP was not reached, and PFS and OS times were 4.0 (95% confidence interval [CI], 3.6-4.5) and 14.8% (95% CI, 12.5-17.2) months, respectively. The 1-year FFLP, PFS, and OS rates were 60% (95% CI, 43.8-76.2), 0%, and 85.7% (95% CI, 75.9-95.5), respectively. Grade 3 or higher hematologic adverse events (AEs) were not observed, but grade 3 nonhematologic AEs unrelated to RT were observed in one patient. The addition of RT may be feasible in patients with advanced HCC treated with atezolizumab plus bevacizumab. However, further studies are required to validate these findings.

Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1highCD11b+ cells elimination in hepatocellular carcinoma.

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1highCD11b+ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8+ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1highCD11b+ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1highCD11b+ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

Progression of hepatocellular carcinoma after radiofrequency ablation: Current status of research.

Hepatocellular carcinoma (HCC) remains an important disease for health care systems in view of its high morbidity, mortality, and increasing incidence worldwide. Radiofrequency ablation (RFA) is preferred to surgery as a local treatment for HCC because it is safer, less traumatic, less painful, better tolerated, causes fewer adverse reactions, and allows more rapid postoperative recovery. The biggest shortcoming of RFA when used to treat HCC is the high incidence of residual tumor, which is often attributed to the vascular thermal deposition effect, the wide infiltration zone of peripheral venules, and the distance between satellite foci and the main focus of the cancer. Recurrence and progression of the residual tumor is the most important determinant of the prognosis. Therefore, it is important to be aware of the risk of recurrence and to improve the efficacy of RFA. This review summarizes the relevant literature and the possible mechanisms involved in progression of HCC after RFA. Current studies have demonstrated that multimodal treatments which RFA combined with other anti-cancer approaches can prevent progression of HCC after RFA.

Outcomes after Stereotactic Body Radiation for Hepatocellular Carcinoma in Patients with Childs Pugh A vs. Childs Pugh B/C Cirrhosis

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) has been shown to be a safe and effective local treatment for hepatocellular carcinoma (HCC). However, limited data exist in patients with CP B and C cirrhosis. The purpose of our study was to compare local control (LC), overall survival (OS), and toxicity outcomes for patients with CP A versus CP B and C cirrhosis. We hypothesized that CP B and C patients would have poorer overall survival, increased toxicity, and similar local control. <h3>Materials/Methods</h3> Patients with HCC who were treated with SBRT were prospectively enrolled into our institutional database from 2012-2021. Patients were separated into cohorts based on their liver function to generate a CP A and CP B/C cohort. LC and OS were evaluated using the Kaplan-Meier method. Local control was evaluated using both radiographic and pathologic data when available. <h3>Results</h3> 78 patients with a total of 94 tumors were included in our analysis with a median follow up of 23.6 months. Median tumor size was 3.6 cm. Median dose delivered was 47.5 Gy in a median of 5 fractions. There were 50 (64%) CP A and 28 (36%) CP B/C patients. The cohorts were comparable in terms of tumor size and baseline AFP. The mean EQD2 was significantly greater in the CP A cohort 85.47 Gy compared to the CP B/C cohort 57.14 Gy (<i>p</i> < .01) Furthermore, a greater proportion of CP B/C patients (64% 18/28) were listed for orthotopic liver transplant compared to CP A patients (30% 15/50) (<i>p</i> =0.004). The estimated 1-year LC rate were similar between the two cohorts with 92.5% LC in the CP A group and 90.9% LC in the CP B/C group (<i>p</i> =0.554). OS was not statistically different between cohorts with an estimated 1-year OS of 85.4% in the CP A group and 60% in the CP B/C group (<i>p</i> =0.225). Radiographic complete response (rCR) was comparable for CP A and CP B/C cohorts at 74% (42/57) and 63% (17/27) respectively. Of the tumors that were pathologically analyzed (CP A n=19; CP B/C n=13), the CP A and CP B/C cohorts had similar pathologic complete response rates of 63% and 62% respectively. 24 (41%) CP A patients and 14 (40%) CP B/C patients developed elsewhere liver tumor recurrence. 9 (15%) CP A patients and 3 (9%) CP B/C patients developed distant metastatic disease. Toxicity rates were low with only 3 patients (6%) in the CP A cohort and 6 patients (21%) in the CP B/C cohort that had grade 3+ adverse events. CP progression occurred in 16% of the CP A group and 29% of the CP B/C group. <h3>Conclusion</h3> Despite receiving lower radiation doses, CP B/C patients had similar LC and pCR rates when compared to CP A patients. OS was not statistically different between the cohorts but analysis was limited due to small numbers and higher number of liver transplant patients in the CP B/C group could also be confounding this result. Although the toxicity rate was reasonable, grade 3+ adverse events and CP progression were higher in CP B/C patients compared to CP A patients.

99m Tc-Macroaggregated Albumin Liver Lung Shunt Study With Uptake Indicative of Patent Falciform Artery.

Intra-arterial injection of radioactive isotope 90-yttrium 90 Y has been used for elective internal radiation therapy for the treatment of localized hepatocellular carcinoma deemed surgically unresectable. It has also been used to treat intrahepatic cholangiocarcinoma and colorectal cancer that has metastasized to the liver. To prepare for 90 Y treatment, preprocedural mapping via hepatic angiography and 99m Tc-macroaggregated albumin liver lung shunt study followed by postprocedural 90 Y SPECT/CT is essential to ensure a targeted therapy. Therapy is contraindicated if lung shunt fraction is greater than 20% for SIR-Spheres. Anatomic variation in hepatic angiography may be present that can lead to complications if unaccounted for.

Percutaneous Thermal Ablation Therapy of Hepatocellular Carcinoma (HCC): Microwave Ablation (MWA) versus Laser-Induced Thermotherapy (LITT).

The purpose of this study is to compare the efficacy and safety of microwave ablation (MWA) versus laser-induced thermotherapy (LITT) as a local treatment for hepatocellular carcinoma (HCC,) with regard to therapy response, survival rates, and complication rates as measurable outcomes. This retrospective study included 250 patients (52 females and 198 males; mean age: 66 ± 10 years) with 435 tumors that were treated by MWA and 53 patients (12 females and 41 males; mean age: 67.5 ± 8 years) with 75 tumors that were treated by LITT. Tumor response was evaluated using CEMRI (contrast-enhanced magnetic resonance imaging). Overall, 445 MWA sessions and 76 LITT sessions were performed. The rate of local tumor progression (LTP) and the rate of intrahepatic distant recurrence (IDR) were 6% (15/250) and 46% (115/250) in the MWA-group and 3.8% (2/53) and 64.2% (34/53) in the LITT-group, respectively. The 1-, 3-, and 5-year overall survival (OS) rates calculated from the date of diagnosis were 94.3%, 65.4%, and 49.1% in the MWA-group and 96.2%, 54.7%, and 30.2% in the LITT-group, respectively (p-value: 0.002). The 1-, 2-, and 3-year disease-free survival (DFS) rates were 45.9%, 30.6%, and 24.8% in the MWA-group and 54.7%, 30.2%, and 17% in the LITT-group, respectively (p-value: 0.719). Initial complete ablation rate was 97.7% (425/435) in the MWA-group and 98.7% (74/75) in the LITT-group (p-value > 0.99). The overall complication rate was 2.9% (13/445) in the MWA-group and 7.9% (6/76) in the LITT-group (p-value: 0.045). Based on the results, MWA and LITT thermal ablation techniques are well-tolerated, effective, and safe for the local treatment of HCC. However, MWA is recommended over LITT for the treatment of HCC, since the patients in the MWA-group had higher survival rates.

Treatment Outcomes of Hepatocellular Carcinoma Patients who underwent Stereotactic Body Radiotherapy

Objective: To evaluate the prognosis of patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).Material and Methods: A retrospective review was performed of the institutional medical records of patients treated with SBRT. The selection criteria were as follows: unresectable HCC confirmed via pathologically, or through imaging, a Karnofsky Performance Status score &gt;60, any Barcelona Clinic Liver Cancer stage, a Child-Pugh score ≤8, and an uninvolved liver volume &gt;700 cm3 . The primary outcomes were local tumor control, overall survival, and progressionfree survival rates. The secondary outcomes were acute adverse events; including general, gastrointestinal, or hepatic disorders; decreased complete blood count; and increased liver function test results.Results: We included 27 HCC patients treated with SBRT; from August 2013 to October 2019. Moreover, 55.6% of patients had received previous treatments for their SBRT-treated lesions. Additionally, the median volume of internal target volume was 40 cm3 , the median uninvolved liver volume was 1,162 cm3 , and the median radiation dose was 40 Gray: given in five fractions. The 1- and 2-year local tumor control rates were both 79.5%. The 1- and 2-year overall survival rates were 58.8% and 27.6%, respectively, and the median survival was 13 months. There were no grade 4 or 5 acute adverse events observed at initiation of treatment or during the follow-up period. Thirteen percent of patients experienced grade 3 acute adverse events. Three patients experienced radiation-induced liver disease.Conclusion: SBRT can be an effective local treatment for hepatocellular carcinoma in carefully selected patients.

Feeding artery ablation before radiofrequency ablation for hepatocellular carcinoma may reduce critical recurrence.

Background and AimPercutaneous radiofrequency ablation (RFA) is a minimally invasive and curative local treatment for hepatocellular carcinoma (HCC). However, serious concerns remain regarding critical recurrences such as metastasis, dissemination, and/or seeding due to RFA. In August 2006, we introduced selective feeding artery ablation before tumor ablation to reduce the risk of critical recurrence by blocking tumor blood flow. The aim of the present study was to clarify whether feeding artery ablation before tumor ablation can reduce the risk of critical recurrence after RFA.MethodsThis study retrospectively analyzed 279 patients with primary, solitary, and hypervascular HCC ≤5 cm in diameter who were treated with RFA alone between April 2001 and August 2013. Critical recurrence was defined as intra‐ or extrahepatic metastasis, dissemination, or seeding that was difficult to treat radically.ResultsOf the 279 HCC patients, 157 patients were treated with conventional RFA alone, and 122 patients underwent RFA with prior feeding artery ablation. Although no significant differences were seen in the rates of local tumor progression‐free survival, overall recurrence‐free survival, or overall survival between a conventional RFA group and a prior feeding artery ablation group, significant differences were seen in rates of critical recurrence‐free survival and cancer‐specific survival (5‐year, 69 vs 81%, P = 0.01 and 76 vs 88%, P = 0.03, respectively). On multivariate analysis, prior feeding artery ablation, tumor diameter, and alpha‐fetoprotein were independent factors related to critical recurrence.ConclusionsFeeding artery ablation before tumor ablation may reduce the risk of critical recurrence.

Efficacy of Local Treatments for Hepatocellular Carcinoma Involving the Inferior Vena Cava and/or Right Atrium.

Major vessel invasion is frequently observed in locally advanced hepatocellular carcinoma (HCC). The most commonly involved major vessel is the portal vein; however, approximately 4% of patients with HCC have inferior vena cava (IVC) and/or right atrium (RA) invasion. Although these conditions have dismal prognoses, local treatments have not been regularly administered because they may affect systemic circulation. Owing to recent technological advances, various local treatments including surgery and external radiotherapy have increasingly been performed in these patients. Since irradiating tumorous lesions in the liver while preserving normal tissues is possible and major vessels are relatively resistant to radiation, external radiotherapy has been a feasible palliative modality for treating vessel-invasive HCC. In addition, systemic fatal complications that were initially a cause of concern have become rare after radiotherapy. While invasive procedures such as extracorporeal circulation or hepatic vascular exclusion may be required, pioneering surgeons have performed surgical resections in selected patients and have obtained promising results. Surgery has shown the best survival outcomes compared to other treatment options including radiotherapy, but the possibility of perioperative morbidity should be considered. In addition, a combination of local treatment and novel systemic agents, which demonstrated better survival and response rates than sorafenib, is expected to maximize therapeutic effects. In this review, we have discussed the most recent treatments for HCC with IVC and/or RA involvement and have provided information intended to guide therapeutic decisions and facilitate future research.

An injectable hydrogel with pH-sensitive and self-healing properties based on 4armPEGDA and N-carboxyethyl chitosan for local treatment of hepatocellular carcinoma

Injectable hydrogels with pH-sensitive and self-healing properties have great application potential in the field of anti-cancer drug carriers. In this work, an injectable hydrogel is prepared using 4armPEG-benzaldehyde (4armPEGDA) and N-carboxyethyl chitosan (CEC) as a new drug carrier. The gelation time, equilibrium swelling rate, degradation time, and dynamic modulus of the injectable hydrogels can be adjusted by merely changing the concentration of 4armPEGDA. The volume of the hydrogel shrinks at pH 5.6 and expands at pH 7.4, which helps to control the release of anti-cancer drug. At pH 5.6, the hydrogels show a fast and substantial Dox release effect, which is five times higher than that at pH 7.4. In vitro cumulative drug release of all the hydrogels reached equilibrium on about the fourth day, and the hydrogel is completely degraded within five days, which contributes to the Dox-loaded hydrogel to further release the remaining Dox. Moreover, the Dox-loaded hydrogel shows a strong inhibitory effect on the growth of human hepatocellular carcinoma cells (HepG2). Finally, the anti-tumor model experiment in vivo demonstrated that the Dox-loaded hydrogel can significantly inhibit tumor growth within five days. Therefore, such injectable hydrogels are excellent carriers for the potential treatment of hepatocellular carcinoma.

Liver resection for recurrent hepatocellular carcinoma after radiofrequency ablation therapy.

Although radiofrequency ablation (RFA) is an effective local treatment of hepatocellular carcinoma (HCC), local recurrence is relatively frequent. We aimed to elucidate the validity of salvage liver resection for recurrent HCC after RFA. Patients who underwent liver resection for recurrent HCC after RFA (LR after RFA) and those who underwent second liver resection for recurrent HCC (second LR) were included. The short-term outcomes were compared between the two groups. The survival rates between the two groups were compared after propensity-score matching to adjust for the variables, including patient background, liver function, and tumor status. Major resection was frequently carried out in the LR after RFA group, but there was no significant difference both in operative data and complication rate between LR after RFA (n = 54) and second LR (n = 266) groups. After a median follow-up period of 1.8years (range, 0.2-10.5), the median overall survival was 4.4years (95% confidence interval [CI], 2.2 - not applicable) and 5.6years (95% CI, 4.5-7.3; P = 0.023) in the LR after RFA group (n = 54) and second LR group (n = 54), respectively, and recurrence-free survival was 1.3years (0.4-2.2) and 1.2years (0.5-1.8, P = 0.469), respectively. The only independent factor for overall survival of the LR after RFA group was local recurrence (hazard ratio, 2.73; 1.06-9.00). Salvage liver resection of recurrent HCC after RFA could be recommended due to the safety of the procedure, especially in patients without local tumor progression after RFA.

Needle track seeding in hepatocellular carcinoma after local ablation by high-dose-rate brachytherapy: a retrospective study of 588 catheter placements.

PurposeNeedle track seeding in the local treatment of hepatocellular carcinoma (HCC) is not yet evaluated for catheter-based high-dose-rate brachytherapy (HDR-BT), a novel local ablative technique.Material and methodsWe report a retrospective analysis of 100 patients treated on 233 HCC lesions by HDR-BT (using 588 catheters in total). No needle or catheter track irradiation was used. Minimum required follow-up with imaging was 6 months. In case of suspected needle track seeding (intra- and/or extrahepatic) in follow-up, image fusion of follow-up CT/MRI with 3D irradiation plan was used to verify the location of a new tumor deposit within the path of a brachytherapy catheter at the time of treatment.ResultsWe identified 9 needle track metastases, corresponding to a catheter-based risk of 1.5% for any location of occurrence. A total of 7 metastases were located within the liver (catheter-based risk, 1.2%), and 2 metastases were located extrahepatic (catheter-based risk, 0.3%). Eight out of 9 needle track metastases were successfully treated by further HDR-BT.ConclusionsThe risk for needle track seeding after interstitial HDR-BT of HCC is comparable to previous reports of percutaneous biopsies and radiofrequency ablation (RFA), especially in case of extrahepatic needle track metastases. To compensate for the risk of seeding, a track irradiation technique similar to track ablation in RFA should be implemented in clinical routine.

Early complications after percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1,843 ablations in 1,211 patients in a single centre: experience over 10 years

To evaluate the incidence of adverse events and associated factors after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma within 30 days. The early complications that occurred within 30 days after RFA at a single institution from January 2000 to July 2010 were reviewed in order to evaluate the morbidity, mortality, and risk factors associated with the complications. In total, 1,211 patients (845 men, 70.5%) with a mean age of 68 years (range, 27-88 years) underwent 1,843 RFA procedures. The overall incidence rate of complications was 6.8% (125 cases). Major complications (n=36, 2%) included liver abscess (n=15, 0.8%), intraperitoneal bleeding (n=8, 0.4%), liver failure (n=5, 0.3%), variceal bleeding (n=3, 0.2%), haemothorax (n=2, 0.1%), cholecystitis (n=2, 0.1%), and bowel perforation (n=1, 0.1%). Among the minor complications (n=89, 4.8%), the most common was the post RFA syndrome accompanied by pain and fever (n=75, 4.1%). Other minor complications included significant pleural effusion (n=7, 0.4%), skin wound infection (n=4, 0.2%), and thermal injuries to the skin (n=3, 0.2%). Procedural infections significantly increased with tumour size (OR=1.379; 95% confidence interval [CI], 1.191-1.579; p<0.001), and multiple overlapping ablations (OR=1.118; 95% CI, 1.019-1.227, p=0.018). Thrombocytopenia (<50,000/μl), prothrombin time, and serum albumin level were significantly associated with post-RFA bleeding episodes (p=0.041, p=0.021, and p=0.003, respectively). The overall mortality rate was 0.3% (three cases of hepatic failure, two case of sepsis, and one case of renal failure). RFA is a safe and effective local treatment for hepatocellular carcinoma. Careful selection of patients and appropriate RFA planning could decrease procedural mortality and morbidity.

Short-Term Results of Laparoscopic Radiofrequency Ablation Using a Multipolar System for Localized Hepatocellular Carcinoma

Background and Aim: Multipolar radiofrequency ablation (RFA) is feasible for the treatment of hepatocellular carcinoma (HCC) for which a large ablative area is planned, and it imposes a light physical burden on patients. Multipolar RFA via the percutaneous approach is performed in the majority of cases, but the efficacy of multipolar RFA with a laparoscopic approach has rarely been studied. This study aimed to evaluate the efficacy and safety of multipolar laparoscopic RFA (LRA) for localized HCC over the short term. Methods: From January 2014 to January 2016, 77 consecutive patients with 130 HCCs treated by multipolar LRA were assessed. One to three bipolar needle applicators were inserted under laparoscopic ultrasonography guidance, regardless of tumor location. We intended to achieve parallel insertions and no-touch ablation as much as possible. Results: The median size of the main tumor was 22 mm (range, 10-42 mm). The median follow-up time was 13.6 months (range, 3.1-24.8 months). In all cases, a sufficient ablative area was obtained as planned, without thermal injury of adjacent organs. During the follow-up period, all patients were alive with no local tumor progression, while intrahepatic recurrence distant from the primary site occurred in 7 patients. The 2-year local tumor progression-free survival rate and overall cancer-free survival rate were 100 and 81.6%, respectively. There were no procedural major complications caused prolonging the hospitalization, and all patients were discharged without subjective symptoms 4-7 days after LRA. Conclusions: Multipolar LRA was efficacious in the treatment of localized HCCs by safely achieving a good ablative area.

Evaluation of contrast-enhanced ultrasonography for hepatocellular carcinoma prior to and following stereotactic body radiation therapy using the CyberKnife® system: A preliminary report.

The CyberKnife® is expected to be a novel local treatment for hepatocellular carcinoma (HCC), however, a long-term follow-up using dynamic computed tomography and magnetic resonance imaging is required to determine the effect of treatment in a number of the affected patients. Therefore, there is a requirement to evaluate procedures for early determination of the effect of CyberKnife treatment. The present study aimed to evaluate the changes in the hemodynamics of the tumors and the hepatic parenchyma surrounding the tumor prior to and following CyberKnife treatment for HCC. A total of 4 HCC patients were enrolled in this study. These patients underwent CyberKnife treatment and were evaluated by image analysis prior to and following treatment using contrast-enhanced ultrasonography (CEUS) with Sonazoid. CEUS was performed prior to treatment, at 2 and 4 weeks post-treatment, and every 4 weeks thereafter for as long as possible. The dynamics of the enhancement of the tumor and the hepatic parenchyma surrounding the tumor in the vascular phase, and the presence or absence of a hypoechoic area in the hepatic parenchyma surrounding the tumor in the post-vascular phase were assessed. Results showed that: i) In the patient with earlier changes, hemodynamic changes were evident in the tumor at 4 weeks and in the hepatic parenchyma surrounding the tumor at 2 weeks post-treatment, respectively; ii) the tumor showed hypoenhancement in all patients; and iii) with regard to findings in the hepatic parenchyma surrounding the tumor, strong hyperenhancement appeared in the vascular phase initially, followed by a hypoechoic area in the post-vascular phase. Evaluation of the hemodynamics of tumors and hepatic parenchyma surrounding the tumor using CEUS with Sonazoid may be therapeutically applicable, as it is less invasive than dynamic computed tomography (CT) and provides an early evaluation of the effectiveness of CyberKnife treatment.

Radiofrequency Ablation for the Local Treatment of Hepatocellular Carcinoma

Radiofrequency Ablation for the Local Treatment of Hepatocellular Carcinoma

Identifying Predictors of Survival in Patients With a Single, Very Small Hepatocellular Carcinoma Who Do Not Undergo Liver Transplantation.

OBJECTIVE/BACKGROUND: Liver transplantation (LT) is the most effective treatment for localized hepatocellular carcinoma (HCC). Unfortunately, donor livers are a scarce resource and can only be offered to a small proportion of HCC patients. Additionally, certain patients with very small HCC and compensated cirrhosis have favorable outcomes with treatment modalities other than LT. Identifying predictors of long-term survival in individuals who undergo non-transplant therapies would allow clinicians to better stratify the utilization of LT. METHODS: From a prospectively collected database of 900 HCC patients, 71 patients were identified with a single HCC ≤2.0 cm. Of these, 11 patients underwent LT (5 were incidentally found to have HCC on explant), 50 patients had non-transplant therapies and 10 had no therapy. This is a retrospective analysis of 37 patients (of the 50 with non-transplant therapies) who received liver resection or radiofrequency ablation (RFA) as their initial treatment and have at least 3 years of follow-up. An analysis of patient characteristics was performed and the odds ratios for achieving overall survival (OS) >3 years were calculated. RESULTS: In this cohort of patients, individuals who underwent LT had a 3-yr OS of 100% (n=10) and 5-yr OS of 100% (n=7). Patients who did not undergo LT had a 3-yr OS 56.76% (n= 37) and 5-yr OS of 41.38% (n=29). Predictors of 3-year survival in non-LT patients included MELD score ≤9 (OR 16.50, 95% CI 3.09-88.04), Child-Pugh score ≤ 6 (OR 7.08, 95% CI 1.6-31.3), BMI ≤ 25 (OR 7.2, 95% CI 1.53-33.85) and platelet count ≥ 100 K (OR 5.5, 95% CI 1.33-22.73). Age, gender, cirrhosis, hepatitis B & C, HCC size ≤1.5 cm, BMI ≥30, hyperlipidemia, normal AFP levels and ethnicity were not predictive of 3 yr survival. Patients who had a MELD score ≤9, platelet count ≥100 and BMI ≤25 were found to have a 3-year OS of 100% (n=11) and 5-year OS of 100% (n=7). CONCLUSION: Patients with a solitary, very small HCC who have a MELD score ≤ 9, BMI ≤25 and platelet count ≥100 K can be treated with RFA or liver resection with excellent 3 and 5-year survival. While these results need to be validated by larger studies, this analysis suggests that patients with these characteristics should not be offered LT in order to optimize utilization of donor organs. DISCLOSURES:Wong, L.: Speaker's Bureau, Bayer Healthcare.