Oligonodular Hepatocellular Carcinoma Research Articles

Liver resection versus radiofrequency ablation or trans-arterial chemoembolization for early-stage (BCLC A) oligo-nodular hepatocellular carcinoma: meta-analysis.

The 2022 Barcelona Clinic Liver Cancer (BCLC) algorithm does not recommend liver resection (LR) in BCLC A patients with oligo-nodular (two or three nodules ≤3 cm) hepatocellular carcinoma (HCC). This sharply contrasts with the therapeutic hierarchy concept, implying a precise treatment order exists within each BCLC stage. This study aimed to compare the outcomes of LR versus radiofrequency ablation (RFA) or trans-arterial chemoembolization (TACE) in BCLC A patients. A meta-analysis adhering to PRISMA guidelines and the Cochrane Handbook was performed. All RCT, cohort and case-control studies that compared LR versus RFA or TACE in oligo-nodular BCLC A HCC published between January 2000 and October 2023 were comprehensively searched on PubMed, Embase, the Cochrane Library and China Biology Medicine databases. Primary outcomes were overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. Risk ratio (RR) was computed as a measure of treatment effect (OS and DFS benefit) to calculate common and random effects estimates for meta-analyses with binary outcome data. 2601 patients from 14 included studies were analysed (LR = 1227, RFA = 686, TACE = 688). There was a significant 3- and 5-year OS benefit of LR over TACE (RR = 0.55, 95% c.i. 0.44 to 0.69, P < 0.001 and RR 0.57, 95% c.i. 0.36 to 0.90, P = 0.030, respectively), while there was no significant 3- and 5-year OS benefit of LR over RFA (RR = 0.78, 95% c.i. 0.37 to 1.62, P = 0.452 and RR 0.74, 95% c.i. 0.50 to 1.09, P = 0.103, respectively). However, a significant 3- and 5-year DFS benefit of LR over RFA was found (RR = 0.70, 95% c.i. 0.54 to 0.93, P = 0.020 and RR 0.82, 95% c.i. 0.72 to 0.95, P = 0.015, respectively). A single study comparing LR and TACE regarding DFS showed a significant superiority of LR. The Newcastle-Ottawa Scale quality of studies was high in eight (57%) and moderate in six (43%). In BCLC A oligo-nodular HCC patients, LR should be preferred to RFA or TACE (therapeutic hierarchy concept). Additional comparative cohort studies are urgently needed to increase the certainty of this evidence.

Outcome of Oligonodular Hepatocellular Carcinoma after Hepatectomy

Introduction: Hepatocellular carcinoma (HCC) is a common cancer and is the third most common cause of cancer-related death worldwide. Frequent recurrence of HCC after resection is a major surgical limitation. Early recurrence is the most disappointing outcome after surgery for multinodular HCC. Several studies found good results after hepatectomy for oligonodular (2 or 3 nodules) HCC.&#x0D; Objectives: To observe the recurrence rate three months after hepatectomy for oligonodular HCC and study the possible risk factors.&#x0D; Materials and Methods: The study population consisted of 102 patients with oligonodular HCC and received hepatectomy in Combined Military Hospital (CMH) between July 2011 and July 2017 according to the following criteria: (1) numbers of tumour nodules determined by preoperative imaging (computed tomography or magnetic resonance imaging) and intraoperative exploration; (2) diagnosis of HCC confirmed by postoperative histopathology; (3) incision margins negative; (4) complete clinicopathologic data; (5) adjuvant chemotherapy advised one month after operation. Multicentric occurrence (MO) and intrahepatic metastasis (IM) were determined in each patient according to the histopathologic examination.&#x0D; Results: Among 102 patients, 43(42.2%) had small tumor stain three months after surgery, 22(21.6%) and 21(20.6%) were definded as single and multiple recurrence respectively. The recurrence rate of patients with microvascular involvement was higher (64.3%) than those without (33.8%), (p&lt;0.05). IM or MO, complete tumor capsule or not, number of tumors (2 versus 3), liver condition (cirrhosis versus chronic hepatitis) showed no significant difference.&#x0D; Conclusion: There was a high rate of very early recurrence for patients with oligonodular HCC three months ater hepatectomy, and the hepatic resection seems no-account for these patients regardless of very early recurrence or not a curative resection. Microvascular involvement was a risk factor while IM or MO is not.&#x0D; Journal of Armed Forces Medical College Bangladesh Vol.15 (1) 2019: 55-57

Comparison of the outcome of radiofrequency ablation or hepatic resection between solitary hepatocellular carcinoma and oligonodular hepatocellular carcinoma meeting Milan criteria: a systematic review and meta-analysis

There are more literatures on the comparison of the outcome of small HCC between HR and RFA, but rare is about the comparison of the outcome between small solitary HCC and small oligonodular HCC meeting Milan criteria by HR or by RFA. Thus, the aim of the present study is to evaluate the outcome between small solitary HCC and small oligonodular HCC meeting Milan criteria treated by HR or by RFA. Total eighteen studies including 4,823 patients was included in this study. Among them LR group included 2,564 cases, and RFA group included 2,259 cases. We divided them into small solitary HCC sub-group and small oligonodular HCC sub-group and compared the survival difference between them. In the HR group, 1, 3, and 5 years OS of the small solitary HCC sub-group were 93.9%, 81.3%, and 72.0%, and the small oligonodular HCC sub-group were 83.3%, 70.4%, and 45.4%, respectively. For the DFS in the HR group, 1, 3, and 5 years of the small solitary HCC sub-group were 76.4%, 56.0%, and 44.0%, and 65.9%, 40.7%, and 11.1% of the small oligonodular HCC sub-group, respectively. In the RFA group, 1, 3, and 5 years OS of the small solitary HCC sub-group were 91.2%, 74.1%, and 54.5%, and the small oligonodular HCC sub-group were 82.0%, 55.4%, and 38.2%, respectively. For the DFS in the RFA group, 1, 3, and 5years of the small solitary HCC sub-group were 74.1%, 49.8%, and 22.1%, and 62.6% and 37.3%, 8.2% of the small oligonodular HCC sub-group, respectively.

A multicenter randomized controlled trial to evaluate the efficacy of surgery vs. radiofrequency ablation for small hepatocellular carcinoma (SURF trial).

4002 Background: Surgery (SUR) and radiofrequency ablation (RFA) are both known to be effective therapy for treating patients with small oligonodular hepatocellular carcinoma (HCC), however there is only insufficient evidence about which therapy is more preferred approach. This randomized controlled trial was designed to prospectively compare the efficacy of SUR and RFA as the first approach to primary HCC. Methods: In this open-label trial undertaken at 49 hospital in Japan, we recruited patients having primary HCC with tumor foci numbering less than 3, each measuring 3 cm or less, Child-Pugh score of 7 or less, ages between 20 and 79 year. Before randomization, technical and liver functional feasibility for both treatment arms were confirmed by joint chart review by surgeons and hepatologists. Patients were then randomly assigned in a 1:1 ratio to undergo SUR or RFA, stratified by age, infection of hepatitis-C virus, number of tumors, tumor size and institution. The primary endpoint was recurrence free survival (RFS) and overall survival (OS). Results: Between April 2009 and August 2015, total 308 patients were enrolled to this trial. Because of ineligibility 15 patients were excluded, therefore 145 patients underwent SUR and 148 patients underwent RFA finally. There was no perioperative mortality. Under the median follow-up of 5 years, the 3-year RFS of patients underwent SUR and RFA was 49.8%, 47.7%, respectively (hazard ration [HR] 0.96, 95% CI 0.72-1.28; p = 0.793). OS will be analyzed and published after two years. Conclusions: SUR and RFA were both safe therapeutic approaches and provided equally RFS for early stage HCC smaller than 3 cm. Clinical trial information: UMIN000001795.

Microwave Ablation (MWA): Basics, Technique and Results in Primary and Metastatic Liver Neoplasms - Review Article.

Purpose The locoregional interventional oncological treatment approach is an accepted modality for liver neoplasms, especially for hepatocellular carcinoma (HCC) and oligonodular liver metastases. Materials and Methods The main aim of ablation therapies like microwave ablation (MWA) is to eradicate all malignant cells in a minimally invasive technique under imaging guidance while preserving the healthy tissue with a sufficient safety margin (at least 5 mm) surrounding the ablated lesion. Results Ablation therapy can be performed via a percutaneous, laparoscopic or intraoperative approach under ultrasound, MRI or CT guidance for adequate localization and monitoring of the ablation process. Conclusion Ablation is the method of choice for oligonodular HCCs ≤ 3 cm. The technical success rate varies from 88 % to 98 % and progression-free survival (PFS) at 3 years from 27 % to 91.7 %. The same criteria apply to the therapy of liver metastases. Key Points · Careful selection of patients proves to be essential for optimum results of MWA. · Interventionists should be familiar with all aspects of complication and rapid assessment of imaging methods in order to evaluate induced damage by thermal ablation. · MWA seems to have some advantages over radiofrequency ablation, like shorter ablation time, less pain, less heat sink effect; however, scientific proof is needed. Citation Format · Vogl TJ, Nour-Eldin A, Hammerstingl RM et al. Microwave Ablation (MWA): Basics, Technique and Results in Primary and Metastatic Liver Neoplasms - Review Article. Fortschr Röntgenstr 2017; 189: 1055 - 1066.

Is resectable hepatocellular carcinoma a contraindication to liver transplantation? A novel decision model based on “number of patients needed to transplant” as measure of transplant benefit

Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad outcome. Although largely used in medical literature, there are no studies measuring the benefit of liver transplantation (LT) over hepatic resection (HR) for hepatocellular carcinoma (HCC) in terms of "Number of patients needed to transplant (NTT)." Child-Turcotte-Pugh (CTP) Classes B-C, very large (>10 cm) and multi-nodular (>2 nodules) tumours, macroscopic vascular invasion and extra-hepatic metastases. 1028 HCC cirrhotic patients from one Eastern (n=441) and two Western (n=587) surgical units. Patient survival observed after HR by proportional hazard regression model was compared to that predicted after LT by the Metroticket calculator. The benefit obtainable from LT compared to resection was analysed in relationship with number of nodules (modelled as ordinal variable: single vs. oligonodular), size of largest nodule (modelled as a continuous variable), presence of microscopic vascular invasion (MVI), and time horizon from surgery (5-year vs. 10-year). 330 patients were beyond the Milan criteria (32%) and 597 (58%) had MVI. The prevalence of MVI was 52% in patients within Milan criteria and 71% in those beyond (p<0.0001). In the 5-year transplant benefit analysis, nodule size and HCC number were positive predictors of transplant benefit, while MVI had a strong negative impact on NTT. Transplantation performed as an effective therapy (NTT <5) only in oligonodular HCC with largest diameter >3cm (beyond conventional LT criteria) when MVI was absent. The 10-year scenario increased drastically the transplant benefit in all subgroups of resectable patients, and LT became an effective therapy (NTT <5) for all patients without MVI whenever tumor extension and for oligonodular HCC with MVI within conventional LT criteria. Based on NTT analysis, the adopted time horizon (5-year vs. 10-year scenario) is the main factor influencing the benefit of LT in patients with resectable HCC and Child A cirrhosis.

Recent advances in hepatic resection and liver transplantation for hepatocellular carcinoma

문에 재발의 위험도가 낮은 환자가 간이식의 대상이 된다. For single hepatocellular carcinoma(HCC), hepatic resection (HR) is regarded as the treatment of choice regardless of size when hepatic function is preserved. Systematic HR is preferred, but an individual patient-customized treatment plan for HR is essential to ensure patient safety as well as to achieve oncologic curability. HR can offer an acceptable survival outcome for patients with small oligo-nodular HCCs and well-preserved liver function. For HCC patients with portal vein tumor thrombus, HR with thrombus removal can lead to improved outcomes comparing with non-surgical treatments. Liver transplantation (LT) is a treatment that offers a chance of a cure for HCC and the underlying liver cirrhosis simultaneously, but the availability of liver grafts and the aggressi-veness of tumor recurrence are critical limiting factors of LT for patients with HCC. In Korea, the shortage of deceased donors and strong demand for LT has led to the development of living-donor LT. Considering that HCC recurrence is the most common cause of post-transplant patient death, recipient candidates should be prudently selected through objectively established criteria. The eligibility criteria for LT for HCC are likely to be expanded, but this will require further qualified risk-benefit analyses. HR and LT have complementary roles; thus they should be considered associated treatments rather than mutually exclusive alternatives. A multi-modality treatment strategy, especially for patients with advanced HCC, provides new fields of investigation for diverse indications of HR and LT.

Magnetic Resonance-guided Laser-induced Thermotherapy in Patients With Oligonodular Hepatocellular Carcinoma

To prospectively evaluate the therapeutic potential of magnetic resonance (MR)-guided laser-induced thermotherapy (LITT) in patients with oligonodular hepatocellular carcinoma. A total of 113 patients with 175 intrahepatic lesions were treated with MR-guided LITT. The Nd-YAG laser fiber was introduced with a percutaneously positioned irrigated laser application system. Qualitative and quantitative MR parameters and clinical data were evaluated. Survival data were calculated using the Kaplan-Meier method. All patients tolerated the procedure well under local anesthesia. The total procedure time was 90 minutes. All observed complications were minor and no further treatment was necessary. Online MR thermometry allowed exact visualization of the extension of laser-induced changes and their relationship to the neighboring anatomy. Lesions up to 2 cm in diameter could be efficiently treated with a single laser application; larger lesions were treated with a dual, triple, and quadruple simultaneous application. In 98% of the patients we achieved a complete necrosis of the tumor and up to 5 mm of safety margin. The mean survival rate for all patients, with calculation started on the date of diagnosis of the HCC nodules treated with LITT, was 4.9 years (95% confidence interval, 3.6, 5.1). The median survival rate for all patients, with calculation started on the date of diagnosis of the HCC nodules treated with LITT, was 3.5 years (95% confidence interval, 2.7, 4.2). One-year survival was 95%; 2-year survival 72%, 3-year survival 54%; and 5-year survival 30%. In intrahepatic oligonodular involvement of hepatocellular carcinoma LITT appears to be an effective therapeutic procedure.

Early Recurrence after Curative Resection in Oligonodular Hepatocellular Carcinoma

Often patients experience an unexpected early recurrence after hepatectomy for multinodular HCC. We conducted this retrospective study to observe the recurrence rate within 1 year after hepatectomy for oligonodular HCC (2 or 3 nodules) and investigate the risk factors for early recurrence. The study population consisted of 102 patients with 2 or 3 HCCs that received curative resection between January 2009 and December 2009. Clinicopathological data were collected and subjected to univariate and multivariate analysis. Forty-three (42.2%) patients were diagnosed as with recurrence within 1 year after hepatectomy. According to univariate analysis, the risk factors for early recurrence were alpha-fetoprotein (AFP) >200 ng/mL, microvascular involvement and lack of complete tumor capsule; microvascular involvement was an independent predictive factor for early recurrence by multivariate analysis (HR, 4.02; 95% CI, 1.42-11.39, p=0.009). There was a high rate of early recurrence for patients with oligonodular HCC (2 or 3 nodules) after hepatectomy. Microvascular involvement was an independent predictive factor for early recurrence, and adjuvant therapy, such as TACE, may be considered for those patients af

Liver transplantation and conventional surgery for advanced hepatocellular carcinoma

This study intended to discuss the roles of hepatic resection (HR) and liver transplantation (LT) in patients with advanced hepatocellular carcinoma (HCC) through our experience and literature review. For large HCC > 10 cm, HR is regarded as the treatment of choice when hepatic function is preserved. Considering frequent extrahepatic recurrence and acceptable outcome after curative HR, LT has not been recommended. For multiple HCCs, HR has been attempted in different preferences worldwide. HR can offer acceptable survival outcome for patients with small oligo-nodular HCCs and well-preserved liver function. Recurrence pattern lowers the applicability of salvage LT, thus primary LT is suggested. For HCC patients with major portal vein tumor thrombus, HR with thrombus removal can be performed, in contrast LT is contraindicated. For HCC with bile duct tumor thrombus, aggressive en bloc resection can lead to prolongation of survival. There is no consensus on transplantability of HCC with bile duct tumor thrombus, but complete resection may provide survival gain after LT. In conclusion, HR and LT have complementary roles, thus they should be associated to rather than being opposed. Multi-modality treatment strategy especially, for patients with advanced HCC, provides new fields of investigation for diverse indications of HR and LT.

Radiofrequency ablation after transarterial embolization as therapy for patients with unresectable hepatocellular carcinoma

To evaluate the usefulness of transcatheter arterial embolization (TAE) followed by radiofrequency ablation (RFA) as combined treatment for unresectable hepatocellular carcinoma (HCC). Thirty-six consecutive patients (cirrhosis, Child-Pugh class A or B) with solitary or oligonodular HCC were treated (41 lesions; mean size, 58.9 mm; range, 30-120 mm). RFA was performed after one TAE treatment. Local efficacy was evaluated with multiphasic computed tomography (CT) performed an average of two months after RFA and once during later follow-up. The mean follow-up period was 16 months (range, 2-45 months). Technical success (namely, complete tumor devascularization during the arterial phase) was achieved for 59% of lesions at the first CT evaluation and for 46% at the second evaluation. Among prognostic factors included in the analysis, only lesion diameter (< 50 mm versus > or = 50 mm) was statistically significant in terms of predicting local success (Fisher's exact test: 85% versus 43% at first CT, p<0.01; 70% versus 36% during follow-up, p=0.05). There were no major periprocedural complications. Kaplan-Meier analysis showed survival rates of 84% at 12 months and 57% at 24 months. Combined therapy--TAE then RFA--for unresectable HCC lesions in patients with cirrhosis produces a relatively high complete local response rate compared with TAE or RFA alone. Our results, considered with those from other case series, may help design prospective, randomized clinical trials to test combination therapy versus single-modality therapy in terms of risks and benefits.

Radiofrequency thermal ablation (RFA) after transarterial chemoembolization (TACE) as a combined therapy for unresectable non-early hepatocellular carcinoma (HCC)

The treatment of unresectable "non-early" (according to the BCLC classification) hepatocellular carcinoma (HCC) in cirrhotic patients with transcatheter arterial chemoembolization (TACE) followed by radiofrequency ablation (RFA) is retrospectively evaluated and possible prognostic factors of this combined therapy are investigated. Forty-six consecutive cirrhotic patients (Child-Pugh class A or B) with solitary or oligonodular HCC underwent RFA after TACE. The treated lesions were 51 overall (size 30-80 mm, mean 48.9). RFA was performed by a multitined expandable electrodes device after one TACE administration. Local efficacy was evaluated with multiphasic computed tomography (CT) performed an average of 2 months after treatment and then during follow-up. Patient survival rate was also evaluated (follow-up time 1-51 months, mean 15 months). Technical success (defined as complete devascularization during the arterial phase) was achieved in 34/51 lesions (66.7%) at the first CT check and in 29/51 (56.9%) during the succeeding follow-up. Among the considered prognostic factors, only lesion diameter (< or > = 50 mm) was statistically significant in the Fisher's exact test in terms of local control (85.2 vs. 45.8% at first CT, p=.0065; 70.4 vs. 41.7% during follow-up, p=.051). There were two major complications (6.5%): one hepatic failure and one death. A Kaplan-Meier analysis showed survival rates of 89.7% at 12 months and 67.1% at 24 months. Combined therapy for non-early HCC shows a relatively high complete local response (especially in lesions less than 5 cm in diameter) and promising mid-term clinical success. Its overall usefulness has yet to be established by a larger series and risk-benefit analysis.

Oligonoduläres hepatozelluläres Karzinom (HCC): MR-gesteuerte laserinduzierte Thermotherapie (LITT)

To prospectively evaluate the therapeutic potential of MR-guided laser-induced thermotherapy (LITT) in patients with oligonodular hepatocellular carcinoma. 39 patients with 61 intrahepatic lesions were treated with LITT. The Nd:YAG laser fiber was introduced with a percutaneously positioned irrigated laser application system. Qualitative and quantitative MR parameters and clinical data were evaluated. All patients tolerated the procedure well under local anesthesia. All observed complications were minor and no further treatment was necessary. Online MR thermometry allowed exact visualization. Lesions up to 2 cm in diameter could be efficiently treated with a single laser application, larger lesions were treated simultaneous multiapplication. In 97.5% we achieved a complete necrosis of the tumor and a 5 mm safety margin, resulting in a complete destruction of the tumor without local recurrences. Mean survival was 4.4 years (95% CI: 3.6-5.2 years) after the time of diagnoses of the HCC (Kaplan-Meier-method). In intrahepatic oligonodular involvement of hepatocellular carcinoma LITT appears to be an effective therapeutic procedure with a high tumor control rate and better survival data.