Distant metastasis of hepatocellular carcinoma to Meckel's cave and cranial nerves: A case report and review of literature.

BACKGROUND: Metastasis occurs as a late event in the natural history of hepatocellular carcinoma (HCC), and most patients die of liver failure attributed to the tumor supplanting the liver. Conversely, the brain is a less common metastatic site. CASE SUMMARY: We describe a rare case of hepatitis C virus-related multiple HCC metastasizing to the cavernous sinus, Meckel's cave, and the petrous bone involving multiple cranial nerves in an 82-year-old woman. At admission imaging studies including Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (MRI) revealed multiple HCC nodules in both right and left lobes. Ultrasound guided biopsy of the left lobe revealed moderately differentiated HCC. Molecular targeted therapy with Lenvatinib (8 mg/d for 94 d, per os) and Ramucirumab (340 mg/d and 320 mg/d, two times by intravenous injection) were administered for 4 mo, resulting in progression of the disease. Three months after the start of molecular target therapy, the patient presented with symptoms of hyperalgesia of the right face and limited abduction of the right eye, indicating disturbances in the right trigeminal and abducens nerves. Brain MRI disclosed a mass involving the cavernous sinus, Meckel's cave and the petrous bone. Contrast-enhanced MRI with gadolinium-chelated contrast medium revealed a well-defined mass with abnormal enhancement around the right cavernous sinus and the right Meckel's cave. CONCLUSION: The diagnosis of metastatic HCC to the cavernous sinus, Meckel's cave, and the petrous bone was made based on neurological findings and imaging studies including MRI, but not on histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Distinct morphology of serotonin-containing enterochromaffin (EC) cells in the rat distal colon.

The present study was performed to examine the distribution and distinct morphology of the serotonin-containing enterochromaffin (EC) cells in the rat distal colon by immunohistochemical and electron microscopic methods. Serotonin-immunohistochemistry revealed that most of the serotonin-immunoreactive EC cells possessed extended cytoplasmic processes. In particular, the immunoreactive EC cells with long processes located along the body of the crypt were characterized by their bipolar processes comprising one with the terminal swellings extending vertically down to the basal crypt and the other running up along the luminal side - in many cases, with the apical ends reaching the glandular lumen. Moreover, a few EC cells had long processes which resembled neuronal processes with varicosities. Electron microscopic observations revealed rod-like, tortuous, oval, or round small pleomorphic granules in the long processbearing EC cells. The cell bodies and processes directly faced the crypt epithelial cells - including the enterocytes and goblet cells on one side and the basement membrane on the opposite side. The accumulation of the granules sometimes appeared within the cytoplasm on the side of the epithelial cells. These findings suggest that serotonin is released from the long processes of the EC cells and directly acts in a paracrine fashion on the crypt epithelial cells to secrete electrolytes and fluids into the colonic lumen. The long cytoplasmic processes of the EC cells may be a major contributor to the serotonininduced secretory events in the rat distal colon.

Morpholino antisense oligomer targeting human midkine: its application for cancer therapy.

Overexpression of a heparin-binding growth factor, midkine (MK), has been observed in many malignancies, making it an attractive therapeutic target. We used morpholino antisense oligomers to downregulate human MK expression in human prostate (PC-3) and colon carcinoma (SW620) cells, and determined the practical advantages of this anticancer therapeutic. Morpholino antisense oligomers directed against MK caused a dramatic and sequence-specific decrease of the target protein level, resulting in the inhibition of growth and anchorage-independent growth of the transfected cells. Furthermore, MK morpholino antisense oligomers exhibited a significant anticancer effect in the PC-3- and SW620-xenograft models. In comparison with phosphorothioate-modified oligodeoxynucleotide, morpholino oligomers showed 2 major advantages, stability and non-toxicity. MALDI-TOF mass spectrometric analysis showed that morpholino antisense oligomers were completely stable in the presence of serum nuclease(s). Serological examinations demonstrated no toxicity of MK morpholino antisense oligomers. Our study indicates that inhibition of MK expression by morpholino antisense oligomer is a promising novel and safe therapeutic strategy for cancers.