Curative Management of Small HCCs: Time to Reconsider the Rules?

With rising incidence and emergence of effective treatment options, the management of hepatocellular carcinoma (HCC) is a complex multidisciplinary process. There is still little consensus and uniformity about clinicopathological staging systems. Resection and liver transplantation have been the cornerstone of curative surgical treatments with recent emergence of ablative techniques. Improvements in diagnostics, surgical techniques, and postoperative care have lead to dramatically improved results over the years. The most appropriate treatment plan has to be individualised and depends on a variety of patient and tumour-related factors. Very small HCCs discovered on surveillance have the best outcomes. Patients with advanced cirrhosis and tumours within Milan criteria should be offered transplantation. Resection is best for small solitary tumours with preserved liver function. Ablative techniques are suitable for low volume tumours in patients unfit for either resection or transplantation. The role of downstaging and bridging therapy is not clearly established.

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Detection of small hepatocellular carcinomas in cirrhotic livers using iodised oil computed tomography

Gut ◽

10.1136/gut.41.3.404 ◽

1997 ◽

Vol 41 (3) ◽

pp. 404-407 ◽

Cited By ~ 20

Author(s):

J Saada ◽

S Bhattacharya ◽

A P Dhillon ◽

R Dick ◽

A K Burroughs ◽

...

Keyword(s):

Computed Tomography ◽

Histological Evaluation ◽

Preoperative Imaging ◽

Patients With Cancer ◽

Contrast Enhanced Ct ◽

Pathological Evaluation ◽

Small Hccs ◽

Cancerous Lesions ◽

Contrast Ct ◽

End Stage

Background—The detection of hepatocellular cancers (HCC) is a major role of preoperative imaging in patients with end stage liver disease being considered for orthotopic liver transplantation (OLT).Aims—To assess the sensitivity of iodised oil computed tomography (IOCT).Patients and methods—A prospective evaluation in 50 consecutive patients undergoing OLT included ultrasound scan, contrast enhanced CT, angiography (with intra-arterial injection of iodised oil), and a second CT (IOCT) 10 days later. Following transplantation the explant liver was serially sectioned for pathological evaluation. Soft tissue radiographs of the liver slices were used to match histological lesions with CT findings.Results—Eleven patients were excluded due to protocol violations. Of the remaining 39, histological evaluation revealed no cancers in 33 explant livers, in keeping with negative preoperative imaging. Six explant livers contained 55 HCCs, 84% of which were less than 1 cm in diameter. Pretransplant IOCT detected 3/6 patients with cancer (50%) but only 7% of cancerous lesions. Ultrasound, contrast CT, and angiography each detected 2/6 patients with cancer and 4% of cancerous lesions.Conclusion—IOCT is an insensitive method for the detection of small HCCs in livers with advanced cirrhosis but in this study was slightly superior to ultrasound, CT, and angiography.

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Stereotactic body radiation therapy for small (≤5 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial

Clinical and Molecular Hepatology ◽

10.3350/cmh.2020.0038 ◽

2020 ◽

Vol 26 (4) ◽

pp. 506-515 ◽

Cited By ~ 1

Author(s):

Sang Min Yoon ◽

So Yeon Kim ◽

Young-Suk Lim ◽

Kang Mo Kim ◽

Ju Hyun Shim ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Radiation Therapy ◽

Phase Ii ◽

Local Control ◽

Stereotactic Body Radiation Therapy ◽

Tertiary Care ◽

Stereotactic Body Radiation ◽

Small Hccs ◽

Modified Recist

Background/Aims: Stereotactic body radiation therapy (SBRT) is used as an alternative ablative treatment in patients with hepatocellular carcinoma (HCC) not suitable for curative treatments. The purpose of this prospective study was to evaluate the long-term efficacy of SBRT for small (≤5 cm) HCCs.Methods: A phase II, single-arm clinical trial on SBRT for small HCCs was conducted at an academic tertiary care center. The planned SBRT dose was 45 Gy with a fraction size of 15-Gy over 3 consecutive days. The primary endpoint was 2-year local control rate. Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and the modified RECIST criteria.Results: Between 2013 and 2016, 50 patients (53 lesions) were enrolled, with a median follow-up period of 47.8 months (range, 2.9–70.6). Patients’ age ranged from 41 to 74 years, and 80% were male. Median tumor size was 1.3 cm (range, 0.7–3.1). The 2- and 5-year local control rates were 100% and 97.1%, respectively. The 5-year overall survival rate was 77.6%. Six months after SBRT, radiologic responses were evident in 44 lesions (83%) according to the RECIST criteria and 49 (92.4%) according to the modified RECIST criteria. None of the patients showed grade ≥3 adverse events.Conclusions: SBRT showed excellent results as an ablative treatment for patients with small HCCs while showing minimal toxicities. SBRT can be a good alternative for both curative and salvage intents in patients with HCCs that are unsuitable for curative treatments.

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Association between Prothrombin Induced by Vitamin K Absence-II (PIVKA-II) and Barcelona Clinic Liver Cancer (BCLC) Stage, Tumor Size, Portal Venous Thrombosis in Hepatocellular Carcinoma Patients

Sains Malaysiana ◽

10.17576/jsm-2021-5002-18 ◽

2021 ◽

Vol 50 (2) ◽

pp. 475-480

Author(s):

Darmadi Darmadi ◽

Riska Habriel Ruslie

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Venous Thrombosis ◽

Vitamin K ◽

Tumor Size ◽

Treatment Options ◽

Barcelona Clinic Liver Cancer ◽

Early Screening ◽

Small Hccs ◽

Portal Venous Thrombosis

Hepatocellular carcinoma is one of the major cancer problems in the world because of the low early screening awareness in patients. Serum alpha-fetoprotein is not adequate as a single screening tool, especially for small HCCs, thus, prothrombin induced by vitamin K absence-II (PIVKA-II) can help in detecting small HCCs. Barcelona Clinic Liver Cancer (BCLC) stage remains to be the preferred HCC classification because it can predict the outcome and help in choosing available treatment options according to stages. This study aims to investigate the association between PIVKA-II levels with BCLC stage, tumor size, portal venous thrombosis in HCC patients. We enrolled patients with newly diagnosed HCC at the Adam Malik General Hospital, Medan, Indonesia from January to December 2018. Patients with HCC were classified according to BCLC stages, findings of portal venous thrombosis and tumor size from triphasic CT scan were noted, and serum PIVKA-II levels were measured. Sixty patients were included in this study. There were significant differences in serum PIVKA-II levels with different stages of BCLC (p < 0.001). Significantly higher serum PIVKA-II levels were detected in patients with portal venous thrombosis (p < 0.001) and larger size tumors (p < 0.003). Our study shows that serum PIVKA-II levels can help to diagnose, differentiate between stages of BCLC, and determine the prognosis in patients with HCC.

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Identification of two HCC phenotypes based on thrombocytopenia.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14720 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14720-e14720

Author(s):

Brian I. Carr

Keyword(s):

Categorical Variables ◽

Tumor Diameter ◽

Continuous Variables ◽

Chi Square ◽

Platelet Counts ◽

Elevated Bilirubin ◽

Size Groups ◽

Chi Square Test ◽

Small Hccs ◽

Maximum Tumor Diameter

e14720 Background: Clinical phenotypes of small and larger HCCs are not well characterized. Aims. To characterize small HCC phenotypes. Methods: A cohort of 430 small HCCs that were diagnosed through screening, were dichotomized by size of < 3cm or > 3cm maximum tumor diameter and compared for radiologic and blood test parameters and analyzed by Chi-square test for categorical variables and Mann-Whitney test for continuous variables. Results: Significant differences between the tumor size groups included AFP values and platelet counts, with thrombocytopenia and elevated bilirubin levels being associated with smaller tumors. In comparing PVT+ and PVT- patients, AFP levels and platelet counts were also significantly different between the 2 groups. Conclusions: Larger tumors were associated with normal platelets and bilirubin levels, compared to smaller tumors that were more typically found in the presence of thrombocytopenia, suggesting that smaller and larger HCCs might have different developmental pathways.

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Increased Expression of Vascular Endothelial Growth Factor and Angiogenesis in the Early Stage of Multistep Hepatocarcinogenesis

Archives of Pathology & Laboratory Medicine ◽

10.5858/2000-124-1061-ieoveg ◽

2000 ◽

Vol 124 (7) ◽

pp. 1061-1065 ◽

Cited By ~ 8

Author(s):

Young Nyun Park ◽

Young-Bae Kim ◽

Kyung Moo Yang ◽

Chanil Park

Keyword(s):

Nuclear Antigen ◽

Low Grade ◽

Vascular Endothelial ◽

High Grade ◽

Vegf Expression ◽

Cell Proliferation Activity ◽

Proliferation Activity ◽

Small Hccs ◽

Endothelial Growth Factor ◽

Hcc Cells

Abstract Background.—Hepatocellular carcinoma (HCC) is known to receive its blood supply principally from the hepatic arteries. Recent studies have reported differences in the vascular supply, especially arterial supply among low- and high-grade dysplastic nodules (DNs) (also referred to as adenomatous hyperplasia and macroregenerative nodules) and HCCs. Increased expression of vascular endothelial growth factor (VEGF) has been reported in HCC. In addition, VEGF may play an important role in the early phases of hepatocarcinogenesis. Methods.—We immunohistochemically stained 7 low-grade DNs, 8 high-grade DNs, 11 early HCCs, 17 small HCCs, and 21 advanced HCCs with antibodies against VEGF, α-smooth muscle actin (to identify unpaired arteries, ie, arteries not accompanied by bile ducts, indicative of angiogenesis), CD34 (as a marker of sinusoidal capillarization), and proliferation cell nuclear antigen. Results.—Expression of VEGF was found in the hepatocytes and HCC cells. The degree of VEGF expression increased gradually according to the stepwise development of hepatocarcinogenesis. It was higher in high-grade DNs and early HCCs than in low-grade DNs. The hepatocytes and HCC cells adjacent to peliosis and fibrous septa showed stronger VEGF expression. Angiogenesis, unpaired arteries, and sinusoidal capillarization developed from low-grade DNs and gradually increased. It was highest in HCCs. The proliferation cell nuclear antigen labeling indexes of hepatocytes and HCC cells also increased gradually as hepatocarcinogenesis progressed. Small HCCs showed a higher status of neoangiogenesis and cell proliferation activity than advanced HCCs. The degree of VEGF expression was correlated with angiogenesis and cell proliferation activity. Conclusion.—We conclude that VEGF plays a significant role in angiogenesis, growth, and development of HCC.

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Low Alpha-Fetoprotein HCC and the Role of GGTP

The International Journal of Biological Markers ◽

10.5301/jbm.5000092 ◽

2014 ◽

Vol 29 (4) ◽

pp. 395-402 ◽

Cited By ~ 6

Author(s):

Brian I. Carr ◽

Vito Guerra ◽

Edoardo G. Giannini ◽

Fabio Farinati ◽

Francesca Ciccarese ◽

...

Keyword(s):

Survival Rates ◽

Alpha Fetoprotein ◽

Gamma Glutamyl Transpeptidase ◽

Vein Thrombosis ◽

Medical Centers ◽

Tumor Multifocality ◽

Small Hccs ◽

Prognosis Marker ◽

Glutamyl Transpeptidase

Background HCC patients are heterogeneous in terms of both tumor and liver factors. Alpha-fetoprotein (AFP) is an important prognostic tumor marker for those patients with elevated AFP levels. Aims To examine the differences in HCC patients with high or low AFP levels in blood and evaluate the prognostic parameters in low AFP patients. Methods A cohort of 2,440 HCC patients from 11 Italian medical centers was studied. AFP-positive patients were compared to AFP-negative ones, and the blood and tumor parameters of AFP-negative patients were examined. Results Low blood AFP levels were found in 58% of the total cohort, in 64% of patients with small HCCs, and in 51% of patients with large HCCs. In patients with large tumors, platelet and gamma glutamyl transpeptidase (GGTP) levels, tumor multifocality and portal vein thrombosis (PVT) incidence were all greater than in patients with small tumors, regardless of AFP status. Patients with higher AFP levels had worse survival rates than those with low AFP in each tumor size group. In patients with small tumors, the elevated AFP was associated with significantly increased PVT and worse survival. In patients with large tumors, the elevated AFP was associated with significantly higher GGTP, ALKP, and bilirubin levels, as well as with increased PVT and multifocality, and worse survival. Low-AFP patients with high GGTP levels had worse survival than patients with low GGTP levels. Conclusion Patients with low AFP were the majority in this cohort, and patients with elevated GGTP had worse prognosis than those with low GGTP. GGTP may be a useful tumor and prognosis marker in low-AFP patients. AFP-negative patients are important to identify due to their enhanced survival.

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Heterogeneity of Hepatocellular Carcinoma on Imaging

Seminars in Liver Disease ◽

10.1055/s-0039-1693512 ◽

2019 ◽

Vol 40 (01) ◽

pp. 061-069 ◽

Cited By ~ 4

Author(s):

Jordi Rimola

Keyword(s):

Functional Imaging ◽

Tumor Heterogeneity ◽

Imaging Techniques ◽

Tumor Vascularity ◽

Mosaic Pattern ◽

Hepatocellular Carcinomas ◽

Small Hccs ◽

Dynamic Enhancement ◽

Molecular Expression ◽

Different Levels

AbstractTumor heterogeneity in hepatocellular carcinomas (HCC) occurs at different levels. On conventional imaging modalities, the spectrum of tumor heterogeneity is evident in the dynamic enhancement pattern, where the characteristic wash-in and wash-out is present in only 60% of small HCCs. In larger HCCs, heterogeneity within the tumor, known as the mosaic pattern, can reflect the presence of different grades of HCC differentiation. The advent of functional imaging techniques has not improved the diagnostic sensitivity of imaging techniques for the diagnosis of HCC. However, the combination of conventional and functional imaging techniques potentially allows the identification of heterogeneity in tumor vascularity, cellularity, and molecular expression.

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