Liver resection is justified for multinodular hepatocellular carcinoma in selected patients with cirrhosis: A multicenter analysis of 1,066 patients.

BACKGROUND: The role of liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) remains unclear, especially among patients with severe underlying liver disease. We sought to evaluate surgical outcomes among patients with cirrhosis and multinodular HCC undergoing liver resection. METHODS: Using a multicenter database, outcomes among cirrhotic patients who underwent curative-intent resection of HCC were examined stratified according to the presence or absence of multinodular disease. Perioperative mortality and morbidity, as well as overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. RESULTS: Among 1066 cirrhotic patients, 906 (85.0%) had single- or double-nodular HCC (the non-multinodular group), while 160 (15.0%) had multinodular HCC (the multinodular group). There were no differences in postoperative 30-day mortality and morbidity among non-multinodular versus multinodular patients (1.8% vs. 1.9%, P = 0.923, and 36.0% vs. 39.4%, P = 0.411, respectively). In contrast, 5-year OS and RFS of multinodular patients were worse compared with non-multinodular patients (34.6% vs. 58.2%, and 24.7% vs. 44.5%, both P < 0.001). On multivariable analyses, tumor numbers ≥5, total tumor diameter ≥8 cm and microvascular invasion were independent risk factors for decreased OS and RFS after resection of multinodular HCC in cirrhotic patients. CONCLUSIONS: Liver resection can be safely performed for multinodular HCC in the setting of cirrhosis with an overall 5-year survival of 34.6%. Tumor number ≥5, total tumor diameter ≥8 cm and microvascular invasion were independently associated with decreased OS and RFS after resection in cirrhotic patients with multinodular HCC.

Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429.

Long noncoding RNAs (lncRNAs) have been reported to play pivotal roles in a variety of cancers. However, lncRNAs involved in hepatocellular carcinoma (HCC) initiation and progression remain largely unclear. In this study, we identified an lncRNA gradually increased during hepatocarcinogenesis (lncRNA-GIHCG) using publicly available microarray data. Our results further revealed that GIHCG is upregulated in HCC tissues in comparison with adjacent non-tumor tissues. High GIHCG expression is correlated with large tumor size, microvascular invasion, advanced BCLC stage, and poor survival of HCC patients. Functional experiments showed that GIHCG promotes HCC cells proliferation, migration, and invasion in vitro, and promotes xenografts growth and metastasis in vivo. Mechanistically, we demonstrated that GIHCG physically associates with EZH2 and the promoter of miR-200b/a/429, recruits EZH2 and DNMT1 to the miR-200b/a/429 promoter regions, upregulates histone H3K27 trimethylation and DNA methylation levels on the miR-200b/a/429 promoter, and dramatically silences miR-200b/a/429 expression. Furthermore, the biological functions of GIHCG on HCC are dependent on the silencing of miR-200b/a/429. Collectively, our results demonstrated the roles and functional mechanisms of GIHCG in HCC, and indicated GIHCG may act as a prognostic biomarker and potential therapeutic target for HCC. KEY MESSAGE: lncRNA-GIHCG is upregulated in HCC and associated with poor survival of patients. GIHCG significantly promotes tumor growth and metastasis of HCC. GIHCG physically associates with EZH2. GIHCG upregulates H3K27me3 and DNA methylation levels on the miR-200b/a/429 promoter. GIHCG epigenetically silences miR-200b/a/429 expression.

MicroRNA-147 suppresses human hepatocellular carcinoma proliferation migration and chemosensitivity by inhibiting HOXC6.

Patients with hepatocellular carcinoma (HCC) experience poor prognosis and low survival rates. In this study, we explored the molecular mechanism of microRNA-147 (miR-147) in regulating human HCC. We firstly used quantitative RT-PCR (qRT-PCR) to compare the expression levels of miR-147 between 7 HCC and two normal liver cell lines, as well as 10 paired primary HCC tissues and their adjacent non-carcinoma tissues. We found miR-147 was down-regulated in both HCC cell lines and primary HCCs tissues. HCC cell lines HepG2 and HuH7 were transfected with lentiviral vector of miR-147 mimics. We found overexpressing miR-147 significantly inhibited HCC in vitro proliferation and migration, increased 5-FU chemosensitivity, and reduced in vivo tumorigenicity. Luciferase, qRT-PCR and western blot assays showed that HOXC6 was the downstream target of miR-147, and both gene and protein levels of HOXC6 were down-regulated by miR-147 in HCC cells. SiRNA mediated HOXC6 knockdown inhibited in vitro proliferation and migration, and increased 5-FU chemosensitivity in HCC. On the other hand, HOXC6 overexpression reversed the inhibitory effect of miR-147 on HCC in vitro proliferation. Therefore, our results suggest that miR-147 can modulates HCC development through the regulation on HOXC6.

Hepatic resection for multiple hepatocellular carcinoma less than 5 cm: a prospective comparative study.

BACKGROUND/AIMS: Treatment of multiple hepatocellular carcinoma (HCC) remains a critical issue. In addition, the prognosis and prognostic factors of multiple HCC after hepatic resection are rarely prospectively documented. METHODOLOGY: The clinicopathologic and follow-up data of 81 patients who underwent curative resection of HCC between January 2008 and January 2009 were prospectively collected. Patients were categorized according to the size of the largest tumor: group A (n = 40, two or three HCCs with maximum tumor diameter > 3 cm and < or = 5 cm) and group B (n = 41, two or three HCCs with maximum tumor diameter < or = 3 cm). The two groups were compared for clinicopathologic data and survival results. RESULTS: The 1-, 2-, 3-, and 4-year survival rates of group A were 75.0%, 58.0%, 50.0%, and 44.0%, respectively, while the survival rates of group B were 93.0%, 80.0%, 66.0%, and 47.0%, respectively. The 1-, 2-, 3-, and 4-year disease-free survival rates of group A were 43.0%, 30.0%, 23.0%, and 15.0%, respectively, comparing to 71.0%, 54.0%, 44.0%, and 36.0% in group B, respectively. The median overall cumulative survival time of group A and group B were 36.0 and 44.5 months, respectively (P = 0.322). The median disease-free survival time of group A was 10.0 months and was significantly shorter than that of group B (30.0 months, P = 0.011). CONCLUSIONS: Resection may provide comparative survival benefits even for patients with multiple HCCs with maximum tumor diameter > 3 cm and < or = 5 cm.

[Application of total hemihepatic vascular exclusion in liver resection for patients with hepatocellular carcinoma and impaired liver function].

OBJECTIVE: To study the clinical value of total hemihepatic vascular exclusion (THHVE) in liver resection for patients with hepatocellular carcinoma (HCC) and impaired liver function. METHODS: The data of 70 patients who underwent liver resection for HCC with impaired liver function between January 2009 and October 2011 were analyzed retrospectively. THHVE was applied in 38 patients (THHVE group), Pringle maneuver in 25 patients (Pringle group) and no vascular occlusion in 7 patients. In the THHVE group, 36 patients were male, 2 were female, average age was (54 ± 9) years. And in Pringle group, 23 patients were male, 2 were female, average age was (53 ± 10) years. Total intraoperative blood loss, blood transfusion rate, clamping time, postoperative complication rate, postoperative hospital stay and postoperative liver function were compared between the THHVE and Pringle group. RESULTS: Total blood loss ((317 ± 186) ml vs. (506 ± 274) ml, t = -3.025, P = 0.004) and transfusion rate (10.5% vs. 32.0%, χ(2) = 4.509, P = 0.034) were significantly lower in the THHVE group than in the Pringle group. Although the clamping time was longer ((21 ± 5) minutes vs. (17 ± 5) minutes, t = 3.209, P = 0.002), the total bilirubin levels on postoperative day 3 and 7 and ALT levels on postoperative day 1, 3, 7 were significantly lower in the THHVE group than in the Pringle group, and the pre-albumin level on postoperative day 7 was higher in the THHVE group than in the Pringle group. Total complication rate (26.3% vs. 52.0%, χ(2) = 4.291, P = 0.038) and major complication rate (7.9% vs. 28.0%, χ(2) = 4.565, P = 0.033) were lower in the THHVE group than in the Pringle group. And postoperative hospital stay duration was shorter in the THHVE group than in the Pringle group ((14.0 ± 2.6) d vs. (16.4 ± 4.0) d, t = -2.625, P = 0.012). CONCLUSIONS: THHVE is a safe and effective technique in liver resection for patients with HCC and impaired liver function. It is associated with less blood loss, lower transfusion requirements, better postoperative liver function recovery, lower postoperative complication rate and shorter postoperative hospital stay.

Solitary necrotic nodule of the liver: MR findings in 33 pathologically proved lesions.

PURPOSE: To determine characteristic magnetic resonance (MR) imaging features of solitary necrotic nodule of the liver. MATERIALS AND METHODS: MR images features of thirty-two patients (17 men, 15 women; mean age, 43 years; range, 24-76 years) with pathologically proved solitary necrotic nodule of the liver were retrospectively analyzed for number, size, signal intensity features and enhancement patterns. RESULTS: A total of 33 lesions were identified. The mean diameter was 2.3cm (range 1.0-4.5cm). Thirty lesions (90.9%) were 1.0-3.0cm in diameter and only 3 lesions (9.1%) were larger than 3.0cm. On T1-weighted images, solitary necrotic nodule of the liver appeared hypointense in 31 lesions (93.9%) and isointense in 2 lesions (6.1%). On T2-weighted images, 12 (36.4%) lesions were hyperintense, 15 (45.4%) were isointense or invisible and 6 (18.2%) were hypointense. After injection of gadopentetate dimeglumine, all lesions were hypointense and none of them showed enhancement. CONCLUSION: Solitary necrotic nodule of the liver is usually small with the size not exceed 3.0cm in diameter. Absence of enhancement on all dynamic phase after gadopentetate dimeglumine administration may be most characteristic feature of solitary necrotic nodule of the liver on MR images, which may help discriminate this entity from metastatic liver tumors and intrahepatic cholangiocarcinoma.

A let-7/Fas double-negative feedback loop regulates human colon carcinoma cells sensitivity to Fas-related apoptosis.

Interferon-γ (IFN-γ) is considered essential for the regulation of anti-tumor reactions as it sensitizes Fas-related apoptosis in HT29 cells, but the mechanism is unclear. In the current study, our data demonstrated that IFN-γ stimulation and Fas activation suppressed Dicer processing and let-7 microRNA biogenesis, while let-7 microRNA strongly inhibited Fas expression by directly targeting Fas mRNA. Accordingly, our results indicate that Fas and let-7 microRNAs form a double-negative feedback loop in IFN-γ and Fas induced apoptosis in colon carcinoma cell line HT29, which may be an important synergistic mechanism in anti-tumor immune response. We also found that a let-7 microRNA inhibitor increased Fas expression and sensitized cells to Fas-related apoptosis, which may have future implications in colon carcinoma therapy.

Primary hepatic malignant fibrous histiocytoma mimicking cystadenocarcinoma: a case report.

BACKGROUND: Malignant fibrous histiocytoma is the most common sarcoma of soft tissue, which occurs usually in the extremities, but less common in the retroperitoneal space, abdominal cavity or other sites. Primary malignant fibrous histiocytoma of the liver is extremely rare; only 28 cases have been reported to date in the English literature. METHODS: In this report, a case of primary malignant fibrous histiocytoma of the liver was described in terms of clinical presentations, diagnosis and treatment and outcome. RESULTS: A 50-year-old man had a large multicystic-mass lesion in the left lobe of the liver, which was inoperable by laparotomy. Pathological examination of biopsy specimen after operation confirmed a malignant fibrous histiocytoma of storiform-pleomorphic type. The tumor developed rapidly, and the patient died of hepatic failure 2 months after the surgery. CONCLUSIONS: Primary malignant fibrous histiocytoma of the liver is diagnosed in late stage because of its rarity and non-specific presentations. Surgical resection, if feasible, is the first step treatment. The prognosis of primary malignant fibrous histiocytoma of the liver is grim with a median survival of 3 months as reported. Surgeons should be alert to the existence of this type of soft tissue tumor in the liver.