Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review.

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma

Histochemical and immunohistochemical analyses of primary carcinoma of the liver.

Hematoxylin and eosin (H-E) stained liver sections of 47 autopsy cases of hepatic malignancies were examined. There were 43 cases of hepatocellular carcinoma (subtypes of 30 trabecular, 7 solid, 5 pseudoglandular, and one scirrhous carcinoma), 3 of cholangiocellular carcinoma and one of mixed carcinoma. After immunohistochemical staining, benign hepatocytes reacted positively with anti-epithelial membrane antigen (EMA). Hepatocellular carcinoma cells reacted more weakly than benign hepatocytes. It was noted that the microtubular structure, which could not be demonstrated even by alcian blue or cationic ferric hydroxide colloid stabilized with cacodylate (Fe-CaC), was clearly detected with anti-EMA. The EMA-positive microtubular structures may indicate terminal cholangiolar differentiation. Based on EMA, seven more cases formerly classified as hepatocellular carcinoma by H-E were reclassified as mixed carcinoma, totaling eight (17.0%). The histologic classification of &#34;mixed carcinoma&#34; has been 1.5 to 2.0% of primary liver cancers in Japan, but we suggest there may be more cases of &#34;mixed carcinoma&#34; identified in the future. In conclusion, we emphasize that EMA staining is useful for more accurate classification of hepatic tumors.</p

Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma

AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-like1 receptor. It is involved in modulation of pain and cognition. High blood level was reported in patients with acute and chronic pain, and in Wilson disease. An accidental observation led us to investigate nociceptin in hepatocellular carcinoma. METHODS: Plasma nociceptin level was measured by radioimmunoassay, aprotinin was used as protease inhibitor. Hepatocellular carcinoma was diagnosed by laboratory, ultrasound, other imaging, and confirmed by fine needle biopsy. Results were compared to healthy controls and patients with other chronic liver diseases. RESULTS: Although nociceptin levels were elevated in patients with Wilson disease (14.0 +/- 2.7 pg/mL, n = 26), primary biliary cirrhosis (12.1 +/- 3.2 pg/mL, n = 21) and liver cirrhosis (12.8 +/- 4.0 pg/mL, n = 15) compared to the healthy controls (9.2 +/- 1.8 pg/mL, n = 29, P < 0.001 for each), in patients with hepatocellular carcinoma a ten-fold increase was found (105.9 &PLUSMN; 14.4 pg/mL, n = 29, P < 0.0001). High plasma levels were found in each hepatocellular carcinoma patient including those with normal alpha fetoprotein and those with pain (104.9 +/- 14.9 pg/mL, n = 12) and without (107.7 +/- 14.5 pg/mL, n = 6). CONCLUSION: A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding

Hepatocarcinoma with tumor thrombus occupying the right atrium and portal vein in a patient with hereditary hemochromatosis and liver cirrhosis

We present the case of a 46-year old patient with Child-Pugh class C cirrhosis with MEDL-Score 16, and hepatocellular carcinoma invading the inferior vena cava and the right atrium. The etiology of cirrhosis is type 1 hereditary hemochromatosis with positive HFE C282Y/C282Y and H63D/H63D mutations. A systematic review of the literature was performed and only 30 cases of hepatocellular carcinoma with tumor thrombosis extending into the right atrium have been described. To our knowledge, this is the first case that evidences the presence in hereditary hemochromatosis of hepatocellular carcinoma with atypical invasion into the right atrium. Screening of patients with a family history of hereditary hemochromatosis allows detection of the disease in the asymptomatic phase, allowing initiation of early therapy and improved prognosis

Sarcoidosis-associated hepatocellular carcinoma

Sarcoidosis is a systemic granulomatous inflammation of unknown etiology, and seems to involve the liver parenchyma in most cases. However, sarcoidosis-associated hepatocellular carcinoma is rare. We report here a case in which a hepatocellular carcinoma occurred within the liver, which was probably involved as a result of systemic sarcoidosis. A 57-year-old Japanese man had been followed up for 2 years because of diabetic nephropathy and sarcoidosis. On admission for pneumonia, imaging studies revealed an unexpected hepatic tumor. Histology revealed a hepatocellular carcinoma accompanied by T-lymphocytic infiltration and marked granulomatous inflammation, which was surrounding some tumor nodules. The background liver parenchyma exhibited a moderate degree of fibrosis with granulomatous inflammation. The patient had no other apparent liver disease such as viral hepatitis, steatohepatitis, or primary biliary cirrhosis. Therefore, in the present case, sarcoidosis may be considered the probable background etiology for hepatocarcinogenesis

Promotion of proliferation and metastasis of hepatocellular carcinoma by LncRNA00673 based on the targeted-regulation of notch signaling pathway

we read with great interest the paper by Dr. Chen et al1, recently published in European Review for Medical and Pharmacological Sciences and titled ‘‘Promotion of proliferation and metastasis of hepatocellular carcinoma by LncRNA00673 based on the targeted-regulation of notch signaling pathway’’. Authors concluded that lncRNA00673 is highly expressed and may be a potential target for the treatment of Hepatocellular Carcinoma (HCC). Moreover, according to authors, it can promote the proliferation and metastasis of HCC by the regulation of Notch signaling pathway. We congratulate the authors for their interesting work

A case of hepatocellular carcinoma recurring during pregnancy

The hepatocellular carcinoma is more common in African and Asian countries with an incidence in women at around 5.5/10,000. Hepatocellular carcinoma is an aggressive tumour, with high recurrence rates, reaching around 50%. Hepatocellular carcinoma is rare in pregnant women. In the English literature, we have found only one case of hepatocellular carcinoma recurrence during pregnancy that was described in a 39 years old patient with the recurrence occurring during her second pregnancy. In our work, we describe the second case of pregnancy complicated by recurrent, advanced and inoperable hepatocellular carcinoma. We also present a literature review about management challenges and the importance of multi-disciplinary care in pregnant women with hepatocellular carcinoma

The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes

Clinical and pathological evaluation of fibrolamellar hepatocellular carcinoma: a single center study of 21 cases

OBJECTIVES: Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor that differs from conventional hepatocellular carcinoma in several aspects. The aim of this study was to describe the clinical, surgical and histopathological features of fibrolamellar hepatocellular carcinoma and to analyze the factors associated with survival. METHODS: We identified 21 patients with histopathologically diagnosed fibrolamellar hepatocellular carcinoma over a 22-year period. Clinical information was collected from medical records and biopsies, and surgical specimens were reviewed. RESULTS: The median age at diagnosis was 20 years. Most patients were female (67%) and did not have associated chronic liver disease. Most patients had a single nodule, and the median tumor size was 120 mm. Vascular invasion was present in 31% of patients, and extra-hepatic metastases were present in 53%. Fourteen patients underwent surgery as the first-line therapy, three received chemotherapy, and four received palliative care. Eighteen patients had “pure fibrolamellar hepatocellular carcinoma,” whereas three had a distinct area of conventional hepatocellular carcinoma and were classified as having “mixed fibrolamellar hepatocellular carcinoma.” The median overall survival was 36 months. The presence of “mixed fibrolamellar hepatocellular carcinoma” and macrovascular invasion were predictors of poor survival. Vascular invasion was associated with an increased risk of recurrence in patients who underwent surgery. CONCLUSION: Fibrolamellar hepatocellular carcinoma was more common in young female patients without chronic liver disease. Surgery was the first therapeutic option to achieve disease control, even in advanced cases. Vascular invasion was a risk factor for tumor recurrence. The presence of macrovascular invasion and areas of conventional hepatocellular carcinoma were directly related to poor survival