Doxorubicin-loaded Drug-eluting beads Versus Conventional Transarterial Chemoembolization for Nonresectable Hepatocellular Carcinoma

Background/Aims:To compare the efficacy and safety profile of doxorubicin-loaded drug-eluting beads (DEB) to the conventional TACE (C-TACE) in the management of nonresectable hepatocellular carcinoma (HCC).Results:Thirty-five patients (51 procedures) in the DEB-TACE group and 19 patients (25 procedures) in the c-TACE group were included in the analysis. The median follow up time was 61 days (range 24–538 days) in the DEB-TACE group and 86 days (range 3–152 days) for the c-TACE group patients. Complete response (CR), objective response (OR), disease control (DC), and progressive disease (PD) rates were 11%, 24%, 53%, and 47%, respectively, in the DEB = TACE group compared with 4%, 32%, 64%, and 36%, respectively, in the c-TACE group. Mean ALT change from baseline was minimal in the DEB-TACE patients compared with c-TACE group (7.2 vs 79.4 units, P = 0.001). Hospital stay was significantly shorter in the DEB-TACE group (7.8 days vs 11.4 days; P = 0.038). The 2-year survival rate was 60% for the c-TACE patients and 58% for the DEB-TACE (P = 0.4).Conclusions:DEB-TACE compared with c-TACE is associated with lesser liver toxicity benefit, better tolerance, and shorter hospital stay. The two modalities however had similar survival and efficacy benefits.     

Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma

Resection of hepatocellular carcinoma (HCC) offers the only hope for cure. However, in patients undergoing resection, recurrences, in particular, intrahepatic recurrence are common. The effectiveness of transarterial chemoembolization (TACE) as a neoadjuvant therapy for unresectable HCC was exploited by numerous liver units and employed preoperatively in the setting of resectable HCC with an aim to prevent recurrence and prolong survival. A systematic literature search of databases (Medline and PubMed) to identify published studies of TACE administered preoperatively as a neoadjuvant treatment for resectable HCC was undertaken. A systematic review by tabulation of the results was performed with disease‐free survival (DFS) as the primary endpoint. Overall survival (OS), rate of pathological response, impact on surgical morbidity and mortality and pattern of recurrences were secondary endpoints of this review. Eighteen studies; three randomized trials and 15 observational studies were evaluated. This comprised of 3927 patients, of which, 1293 underwent neoadjuvant TACE. The median DFS in the TACE and non‐TACE group ranged from 10 to 46 and 8 to 52 months, respectively, with 67% of studies reporting similar DFS between groups despite higher extent of tumour necrosis from the resected specimens indicating a higher rate of pathological response (partial TACE 27–72% vs. non‐TACE 23–52%; complete TACE 0–28% vs. non‐TACE zero), with no difference in surgical morbidity and mortality outcome. No conclusion could be drawn with respect to OS. Both randomized and non‐randomized trials suggest the use of TACE preoperatively as a neoadjuvant treatment in resectable HCC is a safe and efficacious procedure with high rates of pathological responses. However, it does not appear to improve DFS.     

Hepatocellular cancer: Resection or transplantation

Surgery remains the treatment of choice for hepatocellular carcinoma (HCC). For HCC without underlying cirrhosis resection remains the mainstay treatment option. Prognosis depends on the stage of the tumor. Survival appears to be better for small (less than 5 cm) solitary tumors with negative resection margins and absence of vascular invasion. At present, liver transplantation does not have an established role in the treatment of HCC in a non-cirrhotic liver. Because of the high recurrence rate, it should not be considered for more advanced disease which is not amenable to resection. The surgical approach in cirrhotics depends not only on the stage of the tumor but also on the liver functional reserve. Tumor size, presence of multifocal disease, and vascular invasion determine the risk of HCC recurrence after resection, and the functional stability of the liver determines both resectability and outcome. In societies in which transplantation is not available, small tumors will be treated with liver resection. The outcome in patients with well preserved liver function is relatively good, at least in the medium term. However, recurrent tumor and progressive hepatic decompensation have significant adverse effects on long-term survival. Poor functional reserve may be associated with significant perioperative mortality and lower survival due to progressive liver failure. In our opinion, for small cirrhosis-related HCCs, liver transplantation offers better long-term prospects than resection. Therefore, if liver transplantation is available as an option it should be considered as the treatment of choice, particularly for younger patients with otherwise good life expectancy.     

Transarterial Therapy: An Evolving Treatment Modality of Hepatocellular Carcinoma

Liver cancer is the fifth most common cancer in men, the seventh most common in women, and the third most common cause of death from cancer worldwide. Only 30-40% of liver cancer patients present early enough to undergo curative treatments such as surgery or liver transplantation. Local treatment with radiofrequency ablation or ethanol injection is often reserved for non-surgical candidates with early stages of disease. Transarterial embolization has become a widely accepted treatment for asymptomatic patients with unresectable lesions. This review discusses in details the three major forms of transarterial therapies: Bland embolization, chemoembolization, and radioembolization.     

Hypofractionated stereotactic radiotherapy with and without transarterial chemoembolization for small hepatocellular carcinoma not eligible for other ablation therapies: Preliminary results for efficacy and toxicity

Aim: To investigate the efficacy and toxicity of hypofractionated stereotactic radiotherapy for the treatment of patients presenting with hepatocellular carcinoma (HCC) in a single institutional setting. Methods: Sixteen patients who presented with solitary HCC, including two patients with a tumor thrombus of the portal veins, were treated with stereotactic radiotherapy with or without transarterial chemoembolization. The criteria for stereotactic radiotherapy were existence of technical difficulties for other ablation therapies, inoperable disease or refusal to undergo surgery, tumor staged as Grade A or B according to the Child-Pugh classification, and solitary tumor distant from the gastrointestinal tract and kidney with a tumor volume <100 cm(3). In 14 of 16 patients, a total dose of 35- 50 Gy was delivered in 5-7 fractions over 5-9 days. Results: At the end of a mean follow-up of 612 days (median 611 days; range 244-994 days), all patients were alive. Eight of 16 patients had complete responses and seven others were judged as stable with lipiodol accumulation. In one patient, local recurrence developed after 489 days. Intrahepatic recurrences developed outside the treated volume in six patients and no extrahepatic metastases developed during follow-up. No serious treatment-related toxic manifestations developed. Conclusions: Stereotactic radiotherapy for HCC with or without transarterial chemoembolization is feasible therapy and provides good local control with a short treatment period. Stereotactic radiotherapy may be of clinical benefit in patients who are inoperable or for whom there are difficulties in other ablation therapies.     

Interventional treatments for hepatocellular carcinoma

Introduction Hepatocellular carcinoma (HCC) ranks thefifth in overall frequency (the fifth in men and the eighth in women) and fourth inannual mortality. About 372 000 new cases of HCC are diagnosed each year, constituting 4.6% of all new human cancers (6.3% in men and 2.7% in women).[1] Surgical treatments including hepatic resection and liver transplantation are considered the most effective treatments of HCC. However, less than 20% of HCC can be treated surgically because of multi- foc…     

Hepatocellular Carcinoma in a Patient with Tetralogy of Fallot: A Case Report and Literature Review

We herein report a 34-year-old woman born with tetralogy of Fallot who had undergone 5 cardiac repair procedures. She developed liver nodules with congestive cirrhosis secondary to severe mitral regurgitation and an atrial septal defect. A percutaneous liver biopsy showed hepatocellular carcinoma with liver fibrosis, which was treated using transarterial chemoembolization.     

Efficacy and Safety of Ramucirumab in Patients with Unresectable Hepatocellular Carcinoma with Progression after Treatment with Lenvatinib

Objective A survival benefit was demonstrated for ramucirumab (RAM) in patients with unresectable hepatocellular carcinoma (uHCC) and α-fetoprotein (AFP) concentrations ≥400 ng/mL who had previously received sorafenib (SOR). However, it is unclear whether RAM has a similar efficacy in patients with uHCC that progresses after lenvatinib (LEN) treatment. This study aimed to evaluate the early anti-tumor response to RAM as a second-line treatment for advanced uHCC after LEN treatment. Methods We retrospectively assessed the efficacy and safety of RAM at 6 weeks after initiation. The therapeutic effects were evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients We evaluated 7 patients with uHCC who received RAM as a second- or third-line treatment after LEN failure. Results The disease control rate (DCR) was 28.6% (2 of 7 patients). After the initiation of RAM, a rapid disease progression resulted in 1 patient death after 19 days. The median progression-free survival (PFS) was 41 days. There were no grade 3 or 4 treatment-related adverse events. At 6 weeks, there was no deterioration in the modified albumin-bilirubin (mALBI) grade. In patients with an imaging response of stable disease (SD), the rate of AFP production decreased from the baseline. Conclusion RAM may have a therapeutic potential for the suppression of uHCC progression in patients previously treated with LEN, as well as for maintaining the liver function during treatment. Evaluating the AFP trends may therefore be useful for predicting RAM effectiveness.     

Surgical treatment of hepatocellular carcinoma in cirrhosis

Hepatocellular carcinoma is one of the most frequent forms of cancer worldwide and its diagnosis and treatment have changed substantially during the last few years. Recent advances in ultrasonography, spiral computed tomography scan and nuclear magnetic resonance have further simplified the diagnostic approach to hepatocellular carcinoma. Ultrasonography is the reference examination, giving a wide variety of information on tumour size, location, relationship with portal and hepatic veins and splanchnic haemodynamics. Surgical resection and liver transplantation can both be defined as curative treatment while other techniques such as percutaneous ethanol injection and chemoembolization must be considered as palliative. Therapeutic strategies for hepatocellular carcinoma are based upon data concerning the characteristics of the tumour the functional status of non-tumoural liver parenchyma and patients' general conditions. Surgery of hepatocellular carcinoma in cirrhotic liver is mainly restricted by lack of functional hepatic reserve and by the limited capacity of hepatic regeneration. The best surgical results are obtained in early tumoural stages which generally need limited resection. Nevertheless, major liver resections have a specific role in selected cases. Recurrence rate after surgical resection is high and is related to a large number of factors. For this reason, liver transplantation, removing at the same time, the tumour and the underlying disease, is considered, theoretically, the best treatment for hepatocellular carcinoma, but its role is still debated and limited by difficult organ sharing. Integration of present therapeutic schemes are under evaluation with promising preliminary results.     

Ectopic Hepatocellular Carcinoma of the Diaphragm

Ectopic hepatocellular carcinoma (HCC) is very rarely reported. It may occur at various sites. To the best of our knowledge, only one case of ectopic HCC of the diaphragm has been reported. We present another such case with invasion to the lung. Subtotal resection of the left hemidiaphragm, wedge resection of the lung (left lower lobe), and splenectomy were undertaken. Postoperative course was unremarkable; the patient received two courses of adjuvant chemotherapy with cisplatin, VP-16, and bleomycin 1 month later. Follow-up computed tomography and ultrasound were performed 8 months later; there was no local recurrence or distal metastasis.     

Adjuvant transarterial chemoembolization for patients after curative resection of hepatocellular carcinoma: a meta-analysis

Objective: To evaluate the efficacy and safety of adjuvant transarterial chemoembolization (TACE) after curative hepatectomy in improving the survival of patients with primary hepatocellular carcinoma (HCC).

Methods: MEDLINE, Embase and the Cochrane Library were searched for randomized or nonrandomized studies comparing postoperative adjuvant TACE with curative resection alone. Meta-analysis was performed after converting time-event data into a hazard ratio (HR), using an inverse diversity model.

Results: Eight randomized controlled trials (RCTs) and 12 retrospective studies matched the selection criteria, thereby including 3191 patients (779 in RCT, 2412 in observational studies) for the meta-analysis. The meta-analysis showed that receiving adjuvant TACE was associated with improved overall survival (OS, ln[HR]?=?0.70, 95%CI: 0.63–0.78, p?<?.001) and recurrence-free survival (RFS, ln[HR]?=?0.69, 95%CI: 0.63–0.76, p?<?.001) after curative hepatectomies. The results of observational studies were consistent with those of RCTs. Furthermore, meta-regression was utilized to detect study-level factors associated with treatment outcome. It revealed that overall survival was similar among patients treated with various combinations of chemotherapeutic drugs. Subgroup analyses demonstrated that repeated TACE interventions do not provide a higher survival benefit compared with a single course, and patients with a single tumor or tumor size?≥5cm might stand to benefit the most from adjuvant TACE therapy.

Conclusions: This meta-analysis demonstrated that postoperative adjuvant TACE could achieve higher OS and RFS than surgical resection alone. However, these results need to be validated through further high-quality clinical studies.     

Juvenile Hepatocellular Carcinoma in a Healthy Liver

Primary hepatocellular carcinoma (HCC) in patients ＜30 years old is extremely rare. In younger patients, HCC develops against a background of persistent hepatitis B virus infection. We herein report a 23-year-old woman with HCC with all-negative hepatitis virus markers developing in an apparently healthy liver. Imaging studies showed a 50-mm hypervascular mass in segment 4 of the left liver lobe, compatible with HCC. The patient underwent surgical resection. A histological examination showed the presence of poorly differentiated HCC. The patient was diagnosed with HCC developing in a healthy liver. This is an extremely rare case of non-B non-C HCC.