Ikuhiro Yamada

Mao (Ephedra sinica Stapf) protects against D-galactosamine and lipopolysaccharide-induced hepatic failure.

Mao is one component of various traditional herbal medicines. We examined the effects of Mao on an acute liver failure model treated with d-galactosamine (GalN) and lipopolysaccharide (LPS). The lethality of mice administrated Mao with GalN/LPS was significantly decreased compared with that in mice without Mao. Hepatic apoptosis and inflammatory cell infiltration were slight in Mao-treated mice. Serum alanine aminotransferase (ALT) and total bilirubin (T.Bil) activity, tumor necrosis factor alpha (TNF-alpha) levels and caspase 8, 9, and 3 activity in the liver were significantly lower in mice administrated Mao. But, Serum interleukin-6 (IL-6), IL-10 levels and signal transducers and activators of transcription 3 (STAT3) activity in the liver were significantly higher in mice administrated Mao. To investigate the effect of STAT3, we used AG490, which selectively inhibits the activation of Janus kinase (JAK) family tyrosine kinase and inhibits the constitutive activation of STAT3. There was significant aggravation in hepatic apoptosis treated with Mao and AG490 compared with Mao alone. In conclusions, Mao significantly suppressed hepatic apoptosis by inhibition of TNF-alpha production and caspase activity. Furthermore, it is also suggested that Mao, which activates STAT3 induced by IL-6, may be a useful therapeutic tool for fulminant hepatic failure.

Skull metastasis from hepatocellular carcinoma with chronic hepatitis B

A 56-year-old male visited our hospital for evaluation of an occipital mass. Contrast computed tomography showed hypervascular enhancement with osteolytic change in the skull and a huge enhanced mass in the liver. Magnetic resonance imaging showed bone metastasis in the thoracic vertebrae. Assays for hepatitis B surface antigen and hepatitis B core antibody were positive and his liver condition was Child-Pugh grade A. Our diagnosis was hepatocellular carcinoma (HCC) with skull and vertebrae metastases on chronic hepatitis B. He was treated with radiation therapy for bone metastases and transcatheter arterial chemoembolization for HCC. But he developed acute respiratory failure because of aspiration pneumonia, congestion and oedema with haemorrhage of the lungs and died. Dissection showed HCC with multiple bone metastases. The liver tumor was categorized as well-differentiated HCC, Edmondson classification I, trabecular type and pseudoglandular type. In the liver mild infiltration of lymphocytes was seen in Glissons capsules which were significantly enlarged with well preserved limiting plates. Piecemeal necrosis was not obvious. No fibrosis was noted. An 8 cm × 7 cm × 3 cm metastatic lesion had formed in the left occipitotemporal part of the cranial bone. The lesion was osteolytic and showed invasion into the dura mater. Neither the subdural cavity nor the brain showed involvement from the metastatic tumor. However, skull metastasis from HCC is very rare and it affects the patients prognosis and the quality of life. Therefore, it is very important to make an early diagnosis and carry out proper management of skull metastasis from HCC.

Enteral stent placement for malignant afferent loop obstruction by the through-the-scope technique using a short-type single-balloon enteroscope

Background and study aims  A short-type single-balloon enteroscope with a 3.2-mm working channel makes it possible to insert an enteral stent by the through-the-scope technique in patients with malignant afferent loop obstruction. Here, we report five cases of malignant afferent loop obstruction treated with endoscopic enteral stenting. We also propose a new classification for three types of malignant afferent loop obstruction. Type 1: The obstruction site is located distal to the papilla or the bilioenteric anastomosis. Type 2: The obstruction site is located at the papilla or the bilioenteric anastomosis. Type 3: The obstruction site is located between the bilioenteric and pancreaticoenteric anastomosis. The patients with type 1 and 3 were simply treated by inserting an enteral stent endoscopically. The patient with type 2 was treated with an endoscopic enteral stent for malignant afferent loop obstruction and with percutaneous transhepatic biliary stenting for malignant biliary obstruction. Although double stenting for type 2 remains a difficult endoscopic procedure, the endoscopic approach has become the standard approach for malignant afferent loop obstruction.

The impact of modified Glasgow Prognostic Scale as a predictor of survival advantage by FOLFIRINOX in metastatic pancreatic cancer.

440 Background: The superiority of FOLFIRINOX (FFX) therapy over gemcitabine (Gem) alone in patients with metastatic pancreatic cancer (mPC) has been demonstrated in ACCORD11. However, this combina...

Three Patients with Viral Breakthrough During Pegylated Interferon Alpha-2b and Ribavirin Therapy: A Case Series

Introduction A viral breakthrough occurs when a patient achieves a response while on interferon (IFN) therapy and then loses the response despite continued IFN therapy. The cause of viral breakthroughs is not well understood. We encountered three cases with viral breakthrough during treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). Case presentation The three cases were all late virological responders. They did not express anti-IFN alpha-2b antibodies after PEG-IFN and RBV therapy. We analyzed amino acid substitutions of core 70, core 91, and interferon sensitivity-determining region (ISDR), which significantly influence sustained virological response (SVR). Their amino acid substitutions of core 91 were mutant in two cases. Amino acid substitutions of ISDR were wild pattern in two cases. PEG-IFN adherence was above 80% in three cases, and RBV adherence was below 80% in two cases. Conclusion During PEG-IFN and RBV therapy, we should watch for viral breakthrough in late virological responders with mutant type of amino acid substitutions of core 91, wild pattern of amino acid substitution of ISDR, and decrease of RBV adherence. Viral breakthrough is an important problem in PEG-IFN and RBV therapy for chronic hepatitis C. Therefore, it should be investigated more thoroughly in more cases.