Single Hepatocellular Carcinoma Nodule Research Articles

Radiofrequency ablation versus surgical resection for single nodule hepatocellular carcinoma: Long‐term outcomes

BackgroundRadiofrequency ablation (RFA) has been increasingly utilized for treatment of hepatocellular carcinoma (HCC). Long‐term results of RFA, especially in comparison to surgical resection, have not been well described. MethodsEighty‐seven patients with single nodule HCC underwent surgical resection (N=47) or RFA (N=40) during a 9‐year period. RFA was performed for 36 unresectable disease and 4 surgical refusals. Each group was further divided based on tumor size for analysis; Group 1: resection, 5cm (N=18), Group 2: RFA, 5cm (N=26), Group 3: resection, >5cm (N=29) and Group 4: RFA, >5cm (N=14). Follow‐up ranged from 2 to 72 months (median 16 months). Patients' characteristics, local recurrences and overall and disease‐free survivals were compared. ResultsPatients who underwent RFA were older (69 versus 60, p=0.0006), had more advanced Child‐Pugh class and TNM stage (p=0.0002 and p=0.016, respectively), and had smaller tumors (4.6 versus 7.4 cm, p=0.0032). Local recurrence rates were 2% for resection and 10% for RFA (p=0.12). These local and other recurrences were subsequently treated with multimodal therapies as indicated. The median overall and disease‐free survivals were equivalent both between Groups 1 and 2 (49 versus 51 months, p=0.44, 36 versus 22 months, p=0.84), and Groups 3 and 4 (47 versus >63 months, p=0.94, 28 versus 20 months, p=0.67). DiscussionAlthough the groups were not truly comparable, this retrospective study suggests that RFA may offer similar long‐term results to surgical resection for single nodule HCC when combined with multimodal treatments.

Des-γ-carboxy prothrombin in cancer and non-cancer liver tissue of patients with hepatocellular carcinoma

Des-gamma-carboxy prothrombin (DCP), also known as protein induced by vitamin K absence or antagonist II absence (PIVKA-II), has been considered as a useful serum tumor marker for hepatocellular carcinoma (HCC). However, the underlying mechanism causing the elevation of serum DCP levels in HCC patients remains unclear. This study was undertaken to identify the relationship between serum DCP levels and the expression of DCP in cancer and surrounding non-cancer liver tissues of HCC patients. Serum and tissue samples prepared from 92 patients with a single HCC nodule were subjected to clinicopathological study by measuring serum DCP levels and performing immunohistochemical staining for tissue DCP. Serum DCP levels correlated significantly with clinicopathological factors such as hepatitis markers, tumor differentiation, vascular invasion, intrahepatic metastasis, TNM stage, tumor size, tumor recurrence, and patient survival. DCP immunohistochemical staining was positive in cancer tissues for 68 (68/92, 73.9%) patients and in non-cancer tissues surrounding tumors for 24 (24/92, 26.1%) patients. There was no apparent correlation between serum DCP values and the expression of DCP in HCC tissues; however, there was a significant correlation between serum DCP levels and the expression of DCP in non-HCC tissues (p=0.0398). In conclusion, our results suggest that the origin of elevated serum DCP may lie not only in HCC tissue but also in non-cancer tissues. The HCC lesion itself appears to influence the production of DCP in surrounding non-cancer tissues.

Hepatic Resection and Percutaneous Ethanol Injection as Treatments of Small Hepatocellular Carcinoma

Patients with small hepatocellular carcinoma (HCC) are usually treated with hepatic resection or percutaneous ethanol injection (PEI). To compare the effects of hepatic resection versus PEI on survival in a matched case-control study. STUDY Patients with single-nodule HCC (<or=5 cm) who were treated with hepatic resection (cases) or PEI (controls) were eligible. Matching criteria were date of diagnosis, Child-Pugh stage, and age at diagnosis. Kaplan-Meier survival curve of the control group was drawn weighing each stratum by the inverse of its size. Treatments were compared by a stratified Cox's model, adjusted by CLIP score. Of 912 patients, 197 were eligible and 82 (17 cases and 65 controls) were matched, creating 17 strata. Nine (53%) cases and 41 (63%) controls died. Cox model showed no survival difference between the two groups; hazard ratio of PEI versus hepatic resection was 1.04 (95% CI = 0.43-2.52). One- and 3-year survival rates in the hepatic resection and PEI groups were 82% versus 91% and 63% versus 65%, respectively. Patients with small HCC treated with hepatic resection or PEI have similar survival rates. In view of the higher cost and morbidity of hepatic resection, a prospective randomized study is warranted.

Intratumoral genomic heterogeneity in human hepatocellular carcinoma detected by restriction landmark genomic scanning

Background/Aims: One of the unique features of advanced hepatocellular carcinoma (HCC) is the morphological heterogeneity in a single tumor nodule. In order to investigate the intratumoral genomic heterogeneity of HCC, we performed Restriction Landmark Genomic Scanning (RLGS), which allows genomic DNAs to be surveyed at approximately 2000 landmark sites in a single 2-dimensional gel electrophoresis. Methods: RLGS profiles of two regions from a single HCC nodule in six patients were compared with nontumorous liver tissue. Four HCCs consisting of moderately-differentiated cells were separated into several small parts by thin fibrous septa, but not encapsulated. DNA samples were obtained from both parts of these so-called “nodule-in-nodule” HCC. Two HCCs consisting of well-differentiated cells which did not have a definite partition appeared pathologically homogeneous, and two independent regions of the HCC were used for the analysis. Results: All six HCCs demonstrated different RLGS profiles (in total about 160 different spots) from the corresponding non-tumorous liver, and the number of different spots was greater in the 4 moderately-differentiated nodule-in-nodule HCCs (39–68 spots) than in the 2 well-differentiated homogeneous HCCs (6 and 3 spots). RLGS profiles of the two parts were different to each other in all 4 nodule-in-nodule HCCs. On the other hand, two other homogeneous HCCs showed the same RLGS profiles in the two regions. Conclusion: Thus, intratumoral genomic heterogeneity was demonstrated in the advanced HCC samples, and the genomic alterations may relate to the progression of HCC.

Nm23-H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma.

Decreased expression of nm23, a putative metastasis suppressor gene, has been reported to be related to either intrahepatic metastasis or a poor prognosis in hepatocellular carcinoma (HCC). The aim of this study was to elucidate the true role of nm23-H1 expression in both intrahepatic and distant metastases of HCC. Thirteen patients with single-nodule HCC, seven patients with HCC having satellite nodules and seven patients with HCCs having extrahepatic metastases were included in this study. The expression of nm23-H1 protein was immunohistochemically examined in both primary and metastatic nodules. Ten of 13 single-nodule HCCs were found to overexpress nm23-H1 protein. All main tumors, having satellite nodules, were found to overexpress nm23-H protein, except for two HCCs, which only partially expressed nm23-H1 protein. Regarding the nm23-H1 expression in intrahepatic metastases, most nodules overexpressed the protein. The expression of nm23-H1 was found to be low in only one intrahepatic metastasis specimen, while its primary tumor was also found to show a low expression of nm23-H1 protein. Microscopic portal vein invasion was found in three of the five patients studied, and all cancer cells in portal invasion overexpressed nm23-H1 protein. Nm23-H1 protein was expressed in all distant metastatic tumors and the staining intensity of most metastatic nodules was similar to that of the primary tumors. Our study demonstrated that nm23-H1 expression did not always decrease but instead tended to increase at both intrahepatic and extrahepatic metastatic sites. Based on these findings, nm23-H1 expression is not considered to be a reliable indicator of either intrahepatic or distant metastasis in HCC.

Percutaneous Ethanol Injection in the Treatment of Hepatocellular Carcinoma: A Multicenter Survey of Evaluation Practices and Complication Rates

Background: Percutaneous ethanol injection (PEI) has become a widely used procedure in the treatment of hepatocellular carcinoma (HCC). However, the criteria for selecting patients are not standardized, and little information is available about the complications of the procedure. Methods: A questionnaire was sent to 11 experienced Italian centers. It investigated: the size and the number of HCC nodules suitable for treatment and the Child-Pugh risk class of the associated cirrhosis; the performance of the procedure; the number and characteristics of the patients treated; and, finally, any complications. Results: Most of the centers performed PEI in single HCC nodules less than 5 cm in diameter or in multiple nodules if fewer than three, the larger being less than 3 cm. Patients in Child-Pugh's classes A, B, and C with single nodules were generally considered for PEI. A prothrombin time of less than 40% and a platelet count of less than 40, 000/mm3 contraindicated PEI in most of the centers. PEI was generally performed on outpatients, using Chiba or spinal needles. One thousand and sixty-six patients (8118 sessions) were enrolled; 74% had a single HCC nodule and 26% multiple nodules. All except four had cirrhosis; 53% were in Child class A, 38% in class B, and 9% in class C. The mean number of sessions needed to destroy an HCC nodule was 6.7 (range, 2–14), with a mean alcohol injection volume of 5.0 ml per session (range, 2–20 ml). One death (0.09%) and 34 complications (3.2%) were reported. Among the complications we call attention to the hemorrhagic ones (eight cases) and tumoral seeding (seven cases). Severe pain experienced during the maneuver led to discontinuation of the procedure in 3.7% of the patients; 13.5% of the patients required analgesics and 24% had fever after PEI. Conclusions: Some procedural aspects of PEI treatment differ among the various centers: a standardization is advisable. In the present survey PEI is a low-risk technique.