Patients with hepatocellular carcinoma (HCC) and bone metastasis (BM) suffer from greatly reduced life quality and a dismal prognosis. However, BM in HCC has long been overlooked possibly due to its relatively low prevalence in previous decades. To date, no consensus or guidelines have been reached or formulated for the prevention and management of HCC BM. Our narrative review manifests the increasing incidence of HCC BM to sound the alarm for additional attention. The risk factors, diagnosis, prognosis, and therapeutic approaches of HCC BM are detailed to provide a panoramic view of this disease to clinicians and specialists. We further delineate an informative cancer bone metastatic cascade based on evidence from recent studies and point out the main factors responsible for the tumor-associated disruption of bone homeostasis and the formation of skeletal cancer lesions. We also present the advances in the pathological and molecular mechanisms of HCC BM to shed light on translational opportunities. Dilemmas and challenges in the treatment and investigation of HCC BM are outlined and discussed to encourage further endeavors in the exploration of underlying pathogenic and molecular mechanisms, as well as the development of novel effective therapies for HCC patients with BM.
Bone Neoplasms/secondary* ; Carcinoma, Hepatocellular/therapy* ; Humans ; Liver Neoplasms/therapy* ; Prognosis

A 66-year-old female patient was diagnosed with hepatocellular carcinoma accompanied by neuropathic pain induced by a metastatic tumor that compromised root and spinal canal. Although her pain was relieved following medical treatment, breakthrough pain occurring 1-2 times a day was still distressing. Neuropathic pain in her right lower limb caused discomfort and irritability and decreased her quality of life. We had limited options to adjust her prescription drug regime, due to the side effect of these drugs. Although acupuncture therapy was only performed at her home once a week, the efficacy was outstanding. The patient did not report any further instances of breakthrough pain, and she did not require additional bolus morphine. She could comfortably live in her familiar surroundings with her family and did not require any emergency room visits or admission into the hospital during the last month of her life. She had excellent quality of life in the terminal period of her life, and could even participate in a family function during this time. The present case report suggests that acupuncture may have a role in treating neuropathic pain induced by bone metastasis in patients with advanced cancer across clinical and in-home settings.
Acupuncture Therapy ; Aged ; Bone Neoplasms ; complications ; secondary ; Carcinoma, Hepatocellular ; pathology ; Female ; Home Care Services ; Humans ; Liver Neoplasms ; pathology ; Neoplasms ; pathology ; Neuralgia ; etiology ; therapy ; Quality of Life

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

The occurrence of hepatocellular carcinoma (HCC) is closely associated with viral hepatitis or alcoholic hepatitis. Although active surveillance is ongoing in Korea, advanced or metastatic HCC is found at initial presentation in many patients. Metastatic HCC presents with a hypervascular intrahepatic tumor and extrahepatic lesions such as lung or lymph node metastases. Cases of HCC presenting as carcinoma of unknown primary have been rarely reported. The authors experienced a case of metastatic HCC in a patient who presented with a metastatic bone lesion but no primary intrahepatic tumor. This case suggests that HCC should be considered as a differential diagnosis when evaluating the primary origin of metastatic carcinoma.
Antineoplastic Agents/therapeutic use ; Bone Neoplasms/*diagnosis/diagnostic imaging/secondary ; Carcinoma, Hepatocellular/*diagnosis/drug therapy ; Cervical Cord/pathology ; Chemoembolization, Therapeutic ; Gamma Rays ; Humans ; Liver Neoplasms/*diagnosis/drug therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasms, Unknown Primary/pathology ; Niacinamide/analogs & derivatives/therapeutic use ; Pelvic Bones/pathology ; Phenylurea Compounds/therapeutic use ; Tomography, X-Ray Computed

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

Invasion of the bile duct by hepatocellular carcinoma (HCC), which is called intrahepatic bile duct HCC, is rare and has a poor prognosis. Early diagnosis and surgical resection is important for treatment. A 58-year-old man who underwent hepatic resection for HCC 4 years ago and received transarterial chemoembolization (TACE) 2 years after the operation for recurred HCC presented with jaundice. CT scan revealed a tumor in the common bile duct without intrahepatic lesion. Therefore, ERCP was done to perform biopsy and biliary drainage. Histological examination was compatible with hepatocellular carcinoma. However, the tumor could not be visualized at angiography and thus, only transarterial chemoinfusion was performed without embolization. The tumor had disappeared on follow-up CT scan, and the patient has been disease free for 23 months without evidence of recurrence. Herein, we report a case of intrahepatic bile duct HCC which disappeared after ERCP.
Antibiotics, Antineoplastic/therapeutic use ; Bile Duct Neoplasms/diagnosis/pathology/secondary/*therapy ; Bile Ducts, Intrahepatic ; Carcinoma, Hepatocellular/*diagnosis/pathology ; Cholangiopancreatography, Endoscopic Retrograde ; Doxorubicin/therapeutic use ; Embolization, Therapeutic ; Ethiodized Oil/therapeutic use ; Humans ; Jaundice/etiology ; Liver Neoplasms/*diagnosis/pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Stents ; Tomography, X-Ray Computed ; Treatment Outcome

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

OBJECTIVETo investigate the effects of a Chinese herbal extract Songyou Yin on residual hepatocellular carcinoma after chemotherapy in nude mice and the relevant mechanisms.

METHODSOrthotopic nude mouse models bearing residual hepatocellular carcinoma after chemotherapy was established using human liver carcinoma MHCC97L cells. Three different doses of Songyon Yin (2.1 g/kg, 4.2 g/kg and 8.4 g/kg) were administered to the mice in the trial groups by intragastric gavage, respectively. The mice in the control group were administered physiological saline. The tumor growth, metastasis and survival in the mice of each group were recorded. The corresponding mechanisms were studied.

RESULTSThe pulmonary metastasis rates of the control group and 2.1g/kg, 4.2g/kg, 8.4g/kg Songyou Yin treatment group were 86.7%, 73.3%, 40.0%, and 20.0%, respectively, and the survivals of these groups were 53.83 ± 4.71, 56.50 ± 6.09, 66.67 ± 5.61, 81.17 ± 7.36 days, respectively. Compared with the mice in the control group, mice in the 4.2 g/kg, 8.4 g/kg Songyou Yin treatment groups had a lower pulmonary metastasis rate (P = 0.021 and P = 0.001, respectively) and longer survival (P = 0.002 and P = 0.001, respectively). A restoration of E-cadherin expression and a concomitant reduction of N-cadherin expression were detected in the tumors of the 4.2 g/kg and 8.4 g/kg Songyou Yin treatment groups.

CONCLUSIONSSongyou Yin effectively inhibits the invasion and metastasis of the residual hepatocellular carcinoma after chemotherapy in nude mice through attenuating the epithelia-mesenchymal transition and prolongs the survival. Songyon Yin may have potential to promote the efficacy of chemotherapy in hepatocellular carcinoma.

Animals ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Cadherins ; metabolism ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; pathology ; Cell Line, Tumor ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Epithelial-Mesenchymal Transition ; drug effects ; Humans ; Liver Neoplasms ; drug therapy ; metabolism ; pathology ; Lung Neoplasms ; secondary ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neoplasm, Residual ; metabolism ; pathology ; Organoplatinum Compounds ; therapeutic use ; Plants, Medicinal ; chemistry ; Random Allocation ; Survival Rate ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate clinicopathological features of combined hepatocellular-cholangiocarcinoma (C-HCC-CC) with neuroendocrine carcinoma (NEC) differentiation and to review the literature.

METHODSThe clinical data, histological manifestations and immunohistochemical staining results of two cases of C-HCC-CC were analyzed along with a review of the current literature.

RESULTSBoth patients were male with an average age of 57.5 years. Both patients were positive for hepatitis B virus antigen. The tumors of both cases demonstrated the following 3 unequivocal mixed elements: (1) polygonal epithelial tumor cells growing in nests or trabeculae with positive staining for Hepatocyte and AFP, diagnostic of hepatocellular carcinoma (HCC). Cytoplasmic bile production was present in the tumor cells in one case; (2) elliptic or short spindle-shape small blue tumor cells growing in nests or organoid pattern with Syn/CgA/CD56 positivity confirming the presence of neuroendocrine carcinoma (NEC) component; (3) oval tumor cells growing in nests or glandular forms with positivity of CK19 and CK7 confirming differentiation of cholangiocarcinoma (CC). In both cases, the tumors contained at least 20% of each of HCC, NEC and CC components.

CONCLUSIONC-HCC-CC with NEC is a rare form of primary malignancy of the liver with a poor prognosis.

Bile Duct Neoplasms ; Bile Ducts, Intrahepatic ; Bone Neoplasms ; secondary ; CD56 Antigen ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; therapy ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; therapy ; Chemoembolization, Therapeutic ; Cholangiocarcinoma ; metabolism ; pathology ; therapy ; Chromogranin A ; metabolism ; Humans ; Immunohistochemistry ; Keratin-19 ; metabolism ; Keratin-7 ; metabolism ; Ki-67 Antigen ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; therapy ; Male ; Middle Aged ; Mixed Tumor, Malignant ; metabolism ; pathology ; therapy ; Synaptophysin ; metabolism ; alpha-Fetoproteins ; metabolism

No abstract available.
Carcinoma, Hepatocellular/*complications/*secondary/therapy ; Embolization, Therapeutic ; Fatal Outcome ; Hemothorax/diagnosis/*etiology/therapy ; Humans ; Liver Neoplasms/*complications/*pathology/therapy ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Male ; Mediastinum ; Middle Aged ; Paracentesis ; Rupture, Spontaneous ; Tomography, X-Ray Computed ; Treatment Outcome