Granulocyte Colony-Stimulating Factor–Producing Cholangiocellular Carcinoma

A 61-year-old female was admitted to our hospital with epigastric pain and fever. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the left hepatic lobe and swelling of lymph nodes. ¹⁸F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, the patient was diagnosed with a granulocyte colony-stimulating factor (G-CSF)-producing tumor (G-CSF, 213 pg/mL). We performed left trisegmentectomy of the liver, bile duct resection, and lymph node dissection. Histologically, the tumor was a poorly differentiated adenocarcinoma with some lymph nodes metastasis. Immunohistochemical staining of the tumor cells was positive for G-CSF. Therefore, the tumor was diagnosed as G-CSF–producing cholangiocellular carcinoma. The inflammatory reactions and serum G-CSF level transiently improved immediately after surgery. However, 1 month later, the leukocyte count and serum G-CSF level increased again, and recurrence was observed in the remnant liver. The patient died 3 months after the operation. G-CSF–producing cholangiocellular carcinoma is rare. This tumor progresses rapidly, and surgical treatment for advanced condition should be carefully selected.Key words: Granulocyte colony-stimulating factor, Cholangiocellular carcinoma, FDG-PET, Immunohistochemistry, LeukocytosisGranulocyte colony-stimulating factor (G-CSF)-producing tumors were first reported in 1977.¹ G-CSF-producing cholangiocellular carcinomas (CCCs) are rare, with only 5 other reported cases. We herein report a surgical case of G-CSF–producing CCC with early recurrence and include bibliographic comments.     

Role of renal γ-glutamyltransferase activity in hepatic utilization of exogenous glutathione

The importance of renal γ-glutamyltransferase activity in the hepatic utilization of exogenous glutathione (GSH) was evaluated by injecting GSH (1.67mmol/kg body wt) i.v. into bilaterally nephrectomized and sham-operated Sprague-Dawley rats in which endogenous hepatic GSH had been decreased (0.20±0.01μmol/g liver vs 5.87±0.26μmol/g liver in normal controls, mean±SD) by diethylmaleate (0.5 ml/kg body wt, i.p.). Hepatic GSH concentration 60 min after GSH administration was lower in the nephrectomized than in the sham-operated rats (0.87 ±0.25μol/g liver vs 3.08±0.81μmol/g liver,P<0.001), while plasma GSH concentration was higher in the former (4.61±1.07 mM vs 0.11±0.06 mM,P<0.001). In rats with intact kidneys which had been given a γ-glutamyltransferase inhibitor (acivicin, 25 (μmol/kg body wt i.v.) prior to GSH administration, the hepatic GSH concentrations (1.11±0.49μmol/g liver) were comparable to those obtained in the nephrectomized rats. When N-acetylcysteine (1.67 mmol/ kg body wt, i.v.) was administered instead of GSH, the hepatic GSH concentrations were similar in nephrectomized and sham-operated rats (1.54±0.23μmol/g liver vs 2.22±0.58μmol/g liver, NS). The γ-glutamyltransferase activity was much higher in the kidney than in the liver (4460±830IU/kg body wt vs 14±7IU/kg body wt). These results indicate that the kidney plays an essential role in the hepatic utilization of exogenous GSH through its high γ-glutamyltransferase activity.     

Age-associated cardiomyopathy in heterozygous carrier mice of a pathological mutation of carnitine transporter gene,OCTN2

The purpose of this study was to test whether heterozygotes of juvenile visceral steatosis mice, a model for systemic carnitine deficiency, may develop age-associated cardiomyopathy. Tissue morphological observations were carried out by light and electron microscopy to compare the heterozygous and age-matched control mice at periods of 1 and 2 years. Possible effects of the pathological mutation on lipid and glucose levels was also evaluated in humans and mice. Except mild increases in serum cholesterol levels in male heterozygous mice and humans, no changes were found in other factors, indicating that none of the confounding factors seems to be profound. Results demonstrated that heterozygous mice had larger left ventriclular myocyte diameters than the control mice. Morphological changes in cardiac muscles by electron microscopy revealed age-associated changes of lipid deposition and abnormal mitochondria in heterozygous mice. Two out of 60 heterozygous cohort and one out of nine heterozygous trim-kill mice had cardiac hypertrophy at ages older than 2 years. The present study and our previous work suggest that the carrier state of OCTN2 pathological mutations might be a risk factor for age-associated cardiomyopathy.     

Reconstruction of hepatic stellate cell‐incorporated liver capillary structures in small hepatocyte tri‐culture using microporous membranes

In liver sinusoids, hepatic stellate cells (HSCs) locate the outer surface of microvessels to form a functional unit with endothelia and hepatocytes. To reconstruct functional liver tissue in vitro, formation of the HSC‐incorporated sinusoidal structure is essential. We previously demonstrated capillary formation of endothelial cells (ECs) in tri‐culture, where a polyethylene terephthalate (PET) microporous membrane was intercalated between the ECs and hepatic organoids composed of small hepatocytes (SHs), i.e. hepatic progenitor cells, and HSCs. However, the high thickness and low porosity of the membranes limited heterotypic cell–cell interactions, which are essential to form HSC–EC hybrid structures. Here, we focused on the effective use of the thin and highly porous poly( d , l ‐lactide‐co‐glycolide) (PLGA) microporous membranes in SH–HSC–EC tri‐culture to reconstruct the HSC‐incorporated liver capillary structures in vitro. First, the formation of EC capillary‐like structures was induced on Matrigel‐coated PLGA microporous membranes. Next, the membranes were stacked on hepatic organoids composed of small SHs and HSCs. When the pore size and porosity of the membranes were optimized, HSCs selectively migrated to the EC capillary‐like structures. This process was mediated in part by platelet‐derived growth factor (PDGF) signalling. In addition, the HSCs were located along the outer surface of the EC capillary‐like structures with their long cytoplasmic processes. In the HSC‐incorporated capillary tissues, SHs acquired high levels of differentiated functions, compared to those without ECs. This model will provide a basis for the construction of functional, thick, vascularized liver tissues in vitro. Copyright © 2012 John Wiley & Sons, Ltd.     

Hepatic subcapsular hematoma after extracorporeal shock wave lithotripsy (ESWL) for pancreatic stones

We present a patient with complication of huge hepatic subcapsular hematoma after extracorporeal shock wave lithotripsy (ESWL) for pancreatic lithotripsy. The hematoma measured 78–110 mm. Angiography showed a subcapsular hematoma, rather than a hematoma in the liver. In the arterial phase, the distal end of the small vessel showed spotty opacification similar to microaneurysma, suggesting that it was an injury caused by separation of the liver and its capsule, caused by the shock waves. The portal vein and hepatic vein were normal. After 8 weeks of conservative therapy, the hematoma was gradually absorbed and the patient was discharged. Eight months after the accident, the hematoma had decreased to 40 mm in size. After 20 months, it was completely absorbed. The reported rate of renal subcapsular hematoma after ESWL for renal or ureter stones is 0.1%–0.7%. To date, however, only five cases of hepatic subcapsular hematoma after right renal stone disintegration have been reported. This is the first report of hepatic subcapsular hematoma after ESWL for pancreatic stones. Received: September 11, 1998 / Accepted: April 16, 1999