BACKGROUND: Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. METHODS: Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. RESULTS: The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. CONCLUSIONS Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.
Antiviral Agents/therapeutic use* ; Carcinoma, Hepatocellular/surgery* ; Guanine/analogs & derivatives* ; Hepatectomy ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy* ; Humans ; Liver Neoplasms/surgery* ; Retrospective Studies ; Tenofovir/therapeutic use*

BACKGROUND: The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH). METHODS: All subjects were randomized to treatment with either vehicle or GSK923295. Antitumor activity of GSK923295 was assessed by xenograft growth assays. The C57BL/6 mice were subjected to 70% PH and the proliferation was calculated by liver coefficient, further confirmed by immunohistochemistry. The proliferation and cell cycle analysis of liver cell AML12 and HCC cells LM3, HUH7, and HepG2 were investigated using the cell counting kit-8 assay and Flow Cytometry. The chromosome misalignment and segregation in AML12 cells were visualized by immunofluorescence. RESULTS: Treatment with GSK923295 induced antiproliferation in HCC cell lines. It also caused delay on HCC tumor growth instead of regression both in a HCC cell line xenograft model and patient-derived tumor xenograft model. With microarray analysis, CENtromere Protein E was gradually increased in mouse liver after PH. Exposure of liver cells to GSK923295 resulted in delay on a cell cycle in mitosis with a phenotype of misaligned chromosomes and chromosomes clustered. In 70% PH mouse model, GSK923295 treatment also remarkably reduced liver regeneration in later stage, in parallel with the mitotic marker phospho-histone H3 elevation. CONCLUSION The anticancer drug GSK923295 causes a significant delay on HCC tumor growth and liver regeneration after PH in later stage.
Animals ; Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Bridged Bicyclo Compounds, Heterocyclic ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; surgery ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Chromosomal Proteins, Non-Histone ; antagonists & inhibitors ; Electrophoresis, Polyacrylamide Gel ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Liver Neoplasms ; drug therapy ; surgery ; Liver Regeneration ; physiology ; Mice ; Mice, Inbred C57BL ; Real-Time Polymerase Chain Reaction ; Sarcosine ; analogs & derivatives ; therapeutic use ; Xenograft Model Antitumor Assays

Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis.
Adult ; Carcinoma, Hepatocellular/complications/drug therapy/surgery/*therapy ; *Chemoradiotherapy ; Cisplatin/therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil/therapeutic use ; Humans ; Liver Neoplasms/complications/drug therapy/surgery/*therapy ; *Liver Transplantation ; *Living Donors ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; *Portal Vein ; Venous Thrombosis/*complications

Hepatocellular carcinoma (HCC) is well known malignancy with poor prognosis, even after resection of the primary tumor. Sorafenib is the first-line treatment in advanced HCC, but the disease control rate of sorafenib is only 43%. Pulmonary metastasectomy in patients with pulmonary metastasis from HCC has been reported to increase long-term survival compared with systemic chemotherapy. Video-assisted thoracic surgery is considered a reliable approach to the diagnosis and treatment of pulmonary diseases with low complication rate. Pulmonary metastasectomy is not universally accepted because of frequent local recurrence, an uncontrollable primary tumor, and frequent multiple pulmonary metastases in HCC, but outcome of pulmonary metastasectomy and adjuvant sorafenib therapy has not been studied. We experienced a patient who had advanced HCC with pulmonary oligometastasis and received surgical resection of the metastatic pulmonary nodule and sorafenib chemotherapy. In advanced HCC with pulmonary oligometastasis, surgical resection of pulmonary metastasis and sorafenib chemotherapy should be considered.
Carcinoma, Hepatocellular* ; Diagnosis ; Drug Therapy ; Humans ; Lung Diseases ; Metastasectomy ; Neoplasm Metastasis* ; Prognosis ; Recurrence ; Thoracic Surgery, Video-Assisted

OBJECTIVETo investigate the effects of Chinese medicine (CM) herbal treatment based on syndrome differentiation on patients with unresectable hepatocellular carcinoma (HCC).

METHODSA total of 94 patients with unresectable HCC were reviewed between June 2008 and June 2011. Survival analysis was performed between patients who received CM with/without non-curative antitumor treatments of Western medicine (WM) (CM group, 30 cases) and patients who were not treated with CM but with non-curative antitumor treatments of WM or supportive treatment alone (non-CM group, 64 cases). Then, survival analysis was performed between patients treated with CM combined with non-curative antitumor treatments of WM (combination therapy group, 25 cases) and patients with non-curative antitumor treatments of WM alone (non-curative antitumor treatments group of WM, 52 cases). The survival analysis was performed by Kaplan-Meier method and prognostic factors for overall survival (OS) were assessed by the Cox proportional hazards regression model.

RESULTSThe median survival time (MST), 1- and 2-year survival rates of the CM group and the non-CM group were 36 months, 76.7%, 56.1% and 12 months, 48.4%, 26.6%, respectively. The Log-rank test revealed significant difference between the two groups in OS (P<0.01). Cox proportional multivariate analysis revealed that CM was an independent favorable prognostic factor for OS. The MST, 1- and 2-year survival rates of combination therapy group and non-curative antitumor treatments group of WM were 36 months, 76.0%, 55.5% and 13 months, 55.8%, 30.8%, respectively. There was significant difference in OS between the two groups (P=0.004).

CONCLUSIONSCM herbs based on syndrome differentiation have positive effects on survival of patients with unresectable HCC. Furthermore, combination therapy of CM and WM are recommended in HCC treatment.

Adult ; Aged ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; surgery ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms ; drug therapy ; mortality ; surgery ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Survival Analysis ; Syndrome

OBJECTIVETo evaluate the influence of sirolimus on the long-term survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC).

METHODSClinic data of 165 consecutive patients who underwent OLT for HCC from February 2005 to March 2012 was analyzed retrospectively. Among them, 94 patients were treated with a sirolimus-based immunosuppressive protocol after OLT, while the other 71 patients with a FK506-based protocol. Postoperative survival time, survival, disease-free survival (DFS) and tumor recurrence rates between the two groups were compared.

RESULTSThe 2 groups were comparable in all clinicopathologic parameters. The sirolimus-based group had higher patient survival rates than the control group at 1-year (87% vs. 97%, P = 0.03), 2-year (80% vs. 88%), 3-year (76% vs. 85%) and 5-year (63% vs. 75%). The 1-year, 2-year, 3-year and 5-year recurrence rates were 12% vs. 3%, 17% vs. 9%, 21% vs. 9% (P = 0.04) and 31% vs. 16% (P = 0.03). Early and mid-HCC (I - II stage) of 131 cases (control group 61 cases, sirolimus-based group of 70 patients). The 1-year, 2-year, 3-year and 5-year survival rates were 90% vs. 97% , 80% vs. 90%, 78% vs. 86% and 65% vs. 82% (P = 0.04) and recurrence rates were 10% vs. 3%, 16% vs. 8%, 18% vs. 8% and 29% vs. 11% (P = 0.01).

CONCLUSIONThe sirolimus-based immunosuppressive protocol reduce long-term postoperative recurrence rate and improve the survival rate of patients after OLT for HCC significantly (especially early-mid HCC).

Adult ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; surgery ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Liver Neoplasms ; drug therapy ; mortality ; surgery ; Liver Transplantation ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; Sirolimus ; therapeutic use ; Survival Rate ; Tacrolimus ; therapeutic use

BACKGROUNDThe aim of this research was to investigate the impact of post-transplantation adjuvant chemotherapy in the prevention of tumor recurrence and metastasis for hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation.

METHODSA total of 117 patients with HCC exceeding the Milan criteria who had undergone orthotopic liver transplantation (OLT) from August 2002 to February 2009 were enrolled and retrospectively analyzed. The patients were divided into four groups according to chemotherapy regimens and the impact of different chemotherapy regimens on survival, disease-free survival, and adverse effects were compared.

RESULTSOne year survival rates for the gemicitabine, conventional chemotherapy, oxaliplatin plus capecitabine and the best supportive care (BSC) group were 87.5%, 84.2%, 81.6%, and 67.5%. The 3-year survival rates were 48.1%, 25.9%, 31.6%, and 33.7%, respectively for the four groups. One year disease free survival rates for the four groups were 69.8%, 47.4%, 53.8%, and 45.7% respectively. And 3-year disease free survival rates were 43.2%, 23.7%, 23.6%, and 25.1% for the four groups. Stratification analysis showed that the gemcitabine regimen and conventional chemotherapy could significantly improve the survival rate and disease free survival rate for HCC patients who had major vascular invasion and/or microvascular invasion after liver transplantation compared with BSC group.

CONCLUSIONSFor HCC patients beyond Milan criteria, especially who had vascular invasion and/or micorvascular invasion, post-transplantation adjuvant chemotherapy can significantly improve survival. Gemcitabine is a proper regimen for postoperative adjuvant chemotherapy. Conventional chemotherapy can also benefit patients, but the adverse effects are not satisfactory.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; surgery ; Chemotherapy, Adjuvant ; methods ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Doxorubicin ; adverse effects ; therapeutic use ; Female ; Humans ; Liver Neoplasms ; drug therapy ; surgery ; Liver Transplantation ; Male

Transarterial chemoembolization (TACE) is one of the most effective therapies for unresectable hepatocelluar carcinoma or metastatic hypervascular tumors. Abscess occurring in the other organs beside the liver after TACE is a complication that often occurs, sometimes potentially fatal. We report a case of spinal epidural abscess occurred after liver abscess complicated by TACE in a patient with metastatic neuroendocrine tumors to the liver. A 67-year-old female underwent TACE first for the metastatic lesions to liver, with a history of pancreatoduodenectomy for the primary pancreatic neuroendocrine tumor. Four days after TACE, sudden high fever occurred, and liver abscess was found on abdominal CT. Two days later, back pain and radiating pain to the right leg occurred, and lumbar spine MRI showed spinal epidural abscess. After intravenous antibiotics for 8 weeks and partial laminectomy, the patient recovered and was discharged without complications.
Aged ; Anti-Bacterial Agents/therapeutic use ; Carcinoma, Hepatocellular/secondary/*therapy ; Chemoembolization, Therapeutic/*adverse effects ; Epidural Abscess/*etiology/microbiology/surgery ; Escherichia coli/isolation & purification ; Escherichia coli Infections/drug therapy ; Female ; Humans ; Laminectomy ; Liver Abscess/*etiology ; Liver Neoplasms/secondary/*therapy ; Lumbar Vertebrae/microbiology/radiography ; Magnetic Resonance Imaging ; Neuroendocrine Tumors/pathology/surgery ; Pancreaticoduodenectomy ; Tomography, X-Ray Computed

BACKGROUNDDisease recurrence is a main challenge in treatment of hepatocellular carcinoma (HCC). There is no generally accepted method for preventing recurrence of HCC after resection.

OBJECTIVETo compare the efficacy of a traditional herbal medicine (THM) regimen and transarterial chemoembolization (TACE) in preventing recurrence in post-resection patients with small HCC.

DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONSThis is a multicenter, open-label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE.

MAIN OUTCOME MEASURESPrimary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure.

RESULTSAmong the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 (P = 0.048). Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively (P = 0.026). Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar.

CONCLUSIONIn comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-07000033.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; prevention & control ; surgery ; Chemoembolization, Therapeutic ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; prevention & control ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Survival Rate ; Young Adult

Hepatoid adenocarcinoma (HAC) is a rare type of extrahepatic carcinoma whose morphology is similar to that of hepatocellular carcinoma (HCC). Metachronous HCC and HAC in the same patient is extremely rare. The case of a 68-year-old man with chronic hepatitis B infection who had both HCC and HAC of the stomach is reported herein. Nine years previously this patient had been diagnosed with HCC and received a right lobectomy. HCC that recurred at the caudate lobe at 6 months after the operation was successfully treated with transarterial chemoembolization. The patient was followed up regularly thereafter without evidence of tumor recurrence for 9 years. In July 2010 his serum alpha-fetoprotein (AFP) level elevated from 6.5 ng/mL to 625.4 ng/mL, and he developed a probable single metastatic lymph node around the hepatic artery without intrahepatic lesions. Subsequent evaluation with upper endoscopy revealed a 4-cm ulcerative lesion on the antrum of the stomach. Subtotal gastrectomy was performed with lymph-node dissection. Histologic examination revealed a special type of extrahepatic AFP-producing adenocarcinoma-HAC with lymph-node metastasis-which indicates that HAC can be a cause of elevated AFP even in patients with HCC. HAC should be considered if a patient with stable HCC exhibits unusual elevation of AFP.
Adenocarcinoma/*diagnosis/drug therapy/secondary ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Camptothecin/analogs & derivatives/therapeutic use ; Carcinoma, Hepatocellular/*diagnosis/drug therapy/pathology ; Chemoembolization, Therapeutic ; Chemotherapy, Adjuvant ; Fluorouracil/therapeutic use ; Gastroscopy ; Humans ; Leucovorin/therapeutic use ; Liver Neoplasms/*diagnosis/drug therapy/pathology ; Lymph Nodes/surgery ; Lymphatic Metastasis ; Male ; Recurrence ; Silicates/therapeutic use ; Stomach Neoplasms/*diagnosis/drug therapy/secondary ; Titanium/therapeutic use ; Tomography, X-Ray Computed ; alpha-Fetoproteins/*analysis