Antineoplastic Combined Chemotherapy Protocols ; Arsenicals ; administration & dosage ; Carcinoma, Hepatocellular ; drug therapy ; secondary ; Chemoembolization, Therapeutic ; methods ; Humans ; Liver Neoplasms ; Lung Neoplasms ; drug therapy ; secondary ; Niacinamide ; administration & dosage ; analogs & derivatives ; Oxides ; administration & dosage ; Phenylurea Compounds ; administration & dosage

BACKGROUND: Thalidomide has been reported to have antitumor activity for treating metastatic hepatocellular carcinoma (HCC). We evaluated the safety and efficacy of using thalidomide for treating selected patients with unresectable or metastatic HCC, and their disease was refractory to systemic chemotherapy. METHODS: Eight patients with measurable and metastatic HCC that had progressed with prior systemic chemotherapy and who desired further active therapy were enrolled in this study. Thalidomide was given orally at bedtime and it was started at 200 mg/day with no further dose escalation. The response was measured at 2-month intervals. RESULTS: The median age was 44 years (range: 34-52 years) and all the patients had received doxorubicin-based systemic chemotherapy prior to their enrollment. Each patient received thalidomide for a median of 152 days (range: 5-422 days). One partial response was observed (12.5%, 95% CI; 0-42%) along with 4 cases of stable diseases. The most commonly encountered toxicity was somnolence; grade 3 somnolence was noted for one patient, which led to treatment discontinuation. Skin rash was observed in one responding patient. CONCLUSIONS: The results indicate that thalidomide may feasibly offer disease stabilization to metastatic HCC patients. Further dose escalation of thalidomide, or its combination with other chemotherapeutic agents, may be of interest and this should be investigated for treating patients with metastatic HCC.
Treatment Outcome ; Thalidomide/*therapeutic use ; Retrospective Studies ; Pilot Projects ; Middle Aged ; Male ; Lymphatic Metastasis ; Lung Neoplasms/drug therapy/*secondary ; Liver Neoplasms/*drug therapy/pathology ; Immunosuppressive Agents/*therapeutic use ; Humans ; Follow-Up Studies ; Female ; Carcinoma, Hepatocellular/*drug therapy/secondary ; Bone Neoplasms/drug therapy/*secondary ; Adult

INTRODUCTIONPatients with peritoneal metastases (PM) from hepatocellular carcinoma (HCC) often experience a rapid demise even after a complete removal of intrahepatic tumour. Localised PM may now be adequately controlled and managed with cytoreductive surgery (CRS).

TREATMENTThree patients underwent CRS for HCC PM.

OUTCOMEThe first patient survived 21 months from the time of CRS and is alive with the disease. The second patient died 4 months after CRS. The third patient survived 10 months since CRS and is also alive with the disease. Collectively, the survival of 24 patients with HCC PM extracted through a collective literature review who were treated with cytoreductive surgery had 1- and 2-year survival percentages of 83% and 71%, respectively.

CONCLUSIONCareful selection of patients with localised disease to the peritoneal cavity for CRS, taking into consideration the performance status, liver function and tumour biology may lead to a successful outcome in patients with HCC PM.

Carcinoma, Hepatocellular ; drug therapy ; pathology ; surgery ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; surgery ; Male ; Middle Aged ; Peritoneal Neoplasms ; drug therapy ; secondary ; surgery ; Peritoneum ; pathology ; Young Adult

OBJECTIVETo evaluate the safety and efficacy of the combination of transcatheter arterial chemoembolization (TACE) and sorafenib in treatment of hepatocellular carcinoma (HCC) with lung metastasis.

METHODSThirty HCC patients with lung metastasis were treated by the combination of TACE and sorafenib between Oct 2006 and May 2008, including 27 men and 3 women. The age of the patients ranged 32 to 73 years old. Sorafenib was administrated orally at 400 mg, twice daily (the less tolerant patients received 200 mg, bid.), if there was no counterindication, at 3 - 4 weeks after TACE, with every 4 weeks as a course of treatment. The efficacy was evaluated at the end of every course of treatment.

RESULTSThe metastatic lesions in the lung were diminished in 6 cases and stable diseases achieved in 8 cases. The primary liver tumors were stable in 22 cases, including 10 cases achieved by TACE before sorafenib treatment. Eight cases had slightly progressed liver tumors and were treated with 1 - 3 times of TACE in combination with sorafenib. Side effects included skin lesions in 7 cases, hair loss in 6 cases, fatigue in 18 cases, diarrhea in 6 cases, anemia and bone marrow suppression in 5 cases, high blood pressure in 2 cases, and gastrointestinal bleeding in 1 case.

CONCLUSIONThe combination of TACE and sorafenib can be used as an effective treatment for hepatocellular carcinoma patients with lung metastasis, which may stabilize the disease in some patients.

Adult ; Aged ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Benzenesulfonates ; adverse effects ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; secondary ; therapy ; Chemoembolization, Therapeutic ; methods ; Combined Modality Therapy ; Diarrhea ; chemically induced ; Fatigue ; chemically induced ; Female ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; therapy ; Lung Neoplasms ; drug therapy ; secondary ; therapy ; Male ; Middle Aged ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; adverse effects ; therapeutic use

Chronic hepatitis C infection is an important cause of cirrhosis and hepatocellular carcinoma (HCC). Antiviral therapy (AVT) for patients with cirrhosis due to hepatitis C may retard the progression of cirrhosis and prevent both the development of HCC as well as the recurrence of hepatitis C following liver transplantation. This review highlights the issues associated with AVT for patients with compensated and decompensated cirrhosis due to hepatitis C virus.
Antiviral Agents ; therapeutic use ; Carcinoma, Hepatocellular ; prevention & control ; virology ; Disease Progression ; Hepacivirus ; Hepatitis C, Chronic ; complications ; drug therapy ; Humans ; Liver Cirrhosis ; drug therapy ; virology ; Liver Neoplasms ; prevention & control ; virology ; Liver Transplantation ; Secondary Prevention

OBJECTIVETo explore the changes of metastatic potential of residual hepatocellular carcinoma (HCC) after in vivo chemotherapy and its mechanism.

METHODSNude mouse models of orthotopic HCC in the nude mouse livers was established using human hepatocellular carcinoma cell line MHCC97L cells. Oxaliplatin (10 mg/kg, once per week) was administered intraperitoneally (i.p.) to mice in the trial group. Mice in the control group received 0.2 ml of 0.9% sodium chloride on the same days. On day 7 after the third injection, all mice were sacrificed and tumor fragments of equal volume (2 mm×2 mm×2 mm) from each mouse of the oxaliplatin-treated and untreated groups were reinoculated into the livers of each new recipient mouse correspondingly. The growth, metastasis and molecular phenotype of the reinoculated tumors in both groups were determined.

RESULTSIn the new recipient mice, compared with untreated tumors, oxaliplatin pre-treated tumors grew significantly slower [(2624.59 ± 491.60) mm(3) vs. (3849.72 ± 827.09) mm(3), P < 0.001], but gave more spontaneous metastasis to the lung (10/12 vs. 3/12, P = 0.012). A decreased expression of E-cadherin and increased expression of N-cadherin, vimentin and transcription factor Snail were detected in the oxaliplatin pre-treated tumors by immunohistochemistry, which provided the evidence of epithelial mesenchymal transition (EMT) in these tumors.

CONCLUSIONResidual hepatocellular carcinomas after in vivo chemotherapy grow slower but gain enhanced metastatic potential to the lung, associated with epithelial mesenchymal transition.

Animals ; Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Cadherins ; metabolism ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; secondary ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms ; drug therapy ; metabolism ; pathology ; Lung Neoplasms ; drug therapy ; secondary ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Transplantation ; Neoplasm, Residual ; drug therapy ; metabolism ; secondary ; Organoplatinum Compounds ; therapeutic use ; Snail Family Transcription Factors ; Transcription Factors ; metabolism ; Tumor Burden ; Vimentin ; metabolism ; Xenograft Model Antitumor Assays

BACKGROUND/AIMS: Advanced hepatocellular carcinoma (HCC) with multiple lung metastases has a poor prognosis with no effective treatment having been established. This study evaluated the outcomes of systemic chemotherapy for advanced HCC with multiple lung metastases. METHODS: Between January 2000 and December 2006, 68 patients were diagnosed with HCC presenting with multiple lung metastases. Sixteen patients in the terminal stage, such as Child-Pugh grade `C' or an Eastern Cooperative Oncology Group performance status exceeding grade 2, were excluded from the analysis. The following treatment modalities were applied: 26 patients received primary tumor treatment (transarterial chemoembolization or intra-arterial chemotherapy) with systemic chemotherapy, 10 patients received primary treatment only, 8 patients received systemic chemotherapy only, and 8 patients received highly supportive care. The treatment responses and median survival times for the modalities were analyzed and compared. RESULTS: The median age of the 52 analyzed patients (45 males) was 52.4 years. The most common etiology of HCC was chronic hepatitis B virus infection (n=44, 84.6%) followed by hepatitis C virus infection (n=2, 3.8%), with the etiology being unknown in 6 cases (11.5%). The treatment modality had no significant effect on the treatment response rate (P=0.432) or median survival time (133, 66, 74, and 96 days for primary tumor treatment with systemic chemotherapy, primary tumor treatment only, systemic chemotherapy only, and highly supportive care, respectively; P=0.067). CONCLUSIONS: We found that systemic chemotherapy was not effective in treating HCC presenting with multiple lung metastases. Improving the effectiveness of systemic treatment and selecting patients who would benefit from such treatment remains a major challenge.
Adult ; Carcinoma, Hepatocellular/*drug therapy/radiography/*secondary ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Data Interpretation, Statistical ; Female ; Humans ; Liver Neoplasms/*drug therapy/pathology/radiography ; Lung Neoplasms/radiography/*secondary ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Severity of Illness Index ; Survival Analysis ; Treatment Outcome

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.
Acetaminophen ; therapeutic use ; Adult ; Carcinoma, Hepatocellular ; Disease Progression ; Drug Therapy, Combination ; Enzyme Inhibitors ; Glutathione ; Glycolysis ; Hexokinase ; Humans ; L-Lactate Dehydrogenase ; Lactic Acid ; Lung Neoplasms ; secondary ; Male ; Melanoma ; drug therapy ; Necrosis ; Neovascularization, Pathologic ; Pleural Neoplasms ; secondary ; Prognosis ; Pyruvates ; adverse effects ; therapeutic use ; Treatment Outcome

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

Transcatheter arterial chemoembolization (TACE) has been used widely to treat patients with unresectable hepatocellular carcinoma. However, this method can induce various adverse events caused by necrosis of the tumor itself or damage to nontumor tissues. In particular, neurologic side effects such as cerebral infarction and paraplegia, although rare, may cause severe sequelae and permanent disability. Detailed information regarding the treatment process and prognosis associated with this procedure is not yet available. We experienced a case of paraplegia that occurred after conducting TACE through the intercostal artery to treat hepatocellular carcinoma that had metastasized to the rib. In this case, TACE was attempted to relieve severe bone pain, which had persisted even after palliative radiotherapy. A sudden impairment of sensory and motor functions after TACE developed in the trunk below the level of the sternum and in both lower extremities. The patient subsequently received steroid pulse therapy along with supportive care and continuous rehabilitation. At the time of discharge the patient had recovered sufficiently to enable him to walk by himself, although some paresthesia and spasticity remained.
Antiviral Agents/therapeutic use ; Bone Neoplasms/radiography/secondary ; Carcinoma, Hepatocellular/diagnosis/pathology/*therapy ; Catheter Ablation ; Chemoembolization, Therapeutic/*adverse effects ; Hepatitis B/complications/drug therapy ; Humans ; Liver Cirrhosis/etiology ; Liver Neoplasms/diagnosis/pathology/*therapy ; Male ; Middle Aged ; Positron-Emission Tomography ; Soft Tissue Neoplasms/secondary ; Spinal Cord Injuries/*etiology ; Tomography, X-Ray Computed