Histogram analysis of noncancerous liver parenchyma on gadoxetic acid-enhanced MRI: predictive value for liver function and pathology

Purpose

To clarify whether the heterogeneity of hepatic parenchyma in the hepatobiliary phase on gadoxetic acid-magnetic resonance (MR) imaging is correlated with liver damage.

Materials and methods

We retrospectively examined the cases of 98 patients with or without chronic liver disease who underwent gadoxetic acid-enhanced 3T MR imaging before a hepatectomy between December 2010 and October 2014. For the evaluation of the heterogeneity of the signal intensity in the hepatobiliary phase, we placed the region of interest on the hepatic parenchyma, and the skewness and kurtosis were calculated using ImageJ software. A discriminant analysis was performed to examine the routine preoperative laboratory test results including indocyanine green retention at 15 min (ICG-R15), necro-inflammation grade, and liver fibrosis stage according to the METAVIR system: A0/1 (n = 69) and A2 (n = 29); F0/1 (n = 47), F2/3 (n = 31), and F4 (n = 20).

Results

The combination of skewness and kurtosis could discriminate the high ICG-R15 (>20) and low (<20) groups (lambda; 0.925, p = 0.025), necro-inflammatory grade (lambda; 0.926, p = 0.026), and fibrosis stage (lambda; 0.752, p < 0.0001) with statistical significance. The difference between the patients with normal values and those with an abnormal platelet count or aspartate transaminase level was also detectable (lambda; 0.901, p < 0.007, and lambda; 0.864, p = 0.001, respectively).

Conclusion

Histogram analyses of the hepatobiliary phase of gadoxetic acid-enhanced MR imaging have potential as a biomarker for the assessment of liver function, liver fibrosis, and necro-inflammation.

     

Multifaceted therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for acute liver failure in rats

In acute liver failure (ALF), a poorly controlled innate immune response causes massive hepatic destruction, which elicits a systemic inflammatory response, progressive multiple organ failure and ultimate sudden death. Although the liver has inherent tissue‐repairing activities, its regeneration during ALF fails, and orthotopic liver transplantation is the only curative approach. Here we show that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED‐derived serum‐free conditioned medium (SHED–CM) into the d ‐galactosamine‐induced rat model of ALF markedly improved the condition of the injured liver and the animals’ survival rate. The engraftment of infused SHEDs was very low, and both SHEDs and SHED–CM exerted similar levels of therapeutic effect, suggesting that the SHEDs reversed ALF by paracrine mechanisms. Importantly, SHED–CM attenuated the ALF‐induced pro‐inflammatory response and generated an anti‐inflammatory/tissue‐regenerating environment, which was accompanied by the induction of anti‐inflammatory M2‐like hepatic macrophages. Secretome analysis by cytokine antibody array revealed that the SHED–CM contained multiple tissue‐regenerating factors with known roles in anti‐apoptosis/hepatocyte protection, angiogenesis, macrophage differentiation and the proliferation/differentiation of liver progenitor cells. Taken together, our findings suggest that SHEDs produce factors that provide multifaceted therapeutic benefits for AFL. Copyright © 2015 John Wiley & Sons, Ltd.     

Solitary splenic metastasis from early gastric cancer: Report of a case

Solitary metastasis of a malignancy to the spleen is rare. We herein describe a case of splenic metastasis from early gastric cancer. A 76-year-old man underwent an endoscopic mucosal resection (EMR) for early gastric carcinoma in the cardia. Pathologically, the tumor showed invasion into the submucosal layer, and the stump of the surgical specimen appeared to be positive for malignant cells. He thus underwent a proximal gastrectomy with nodal dissection. One year later, serum carcinoembryonic antigen was elevated, and a splenic mass was detected by computed tomography and ultrasonography. Because the tumor increased in size very gradually and no metastatic lesions were detected at the other sites, we performed a splenectomy. The lesion was pathologically diagnosed as metastasis from the previous gastric carcinoma, and the patient remains healthy to date without recurrence, more than 2 years after the splenectomy. When solitary metastasis to the spleen is suspected during the postoperative follow-up of a patient with gastric cancer, a splenectomy is a potentially effective treatment.     

Impact of early elevation of serum bilirubin during treatment with pegylated interferon and ribavirin in patients with chronic hepatitis C

Aim: Hemolytic anemia is a well‐known adverse effect of interferon and ribavirin combination treatment. Herein, we analyzed the impact of early elevation of serum bilirubin level as a marker for predicting severe anemia during treatment. Methods: We studied 245 chronic hepatitis C patients who received pegylated interferon and ribavirin combination treatment, and divided them using two different threshold levels: (i) elevation of total bilirubin of 0.5 mg/dL or more within 1 week of starting treatment; and (ii) drop of hemoglobin (Hb) by 3 g/dL or more within 4 weeks of starting treatment. We compared the dynamics in each group and then investigated independent factors for predicting a severe Hb drop (≥3 g/dL) at 4 weeks after beginning treatment and dose reduction of ribavirin. Results: Total bilirubin levels at 1 week were significantly higher in patients with a Hb drop of 3 g/dL or more as compared to those with a drop of less than 3 g/dL (P < 0.0001). Hb levels at 4 weeks were significantly lower in the group of 0.5 mg/dL or more increase of total bilirubin levels than in the group with a less than 0.5 mg/dL increase (P < 0.0001). Therefore, elevation of total bilirubin after 1 week of treatment was shown to be an independent factor for predicting severe Hb drop (≥3 g/dL) at 4 weeks (P < 0.0001), and dose reduction of ribavirin during treatment (P = 0.0321). Conclusion: Early elevation of serum bilirubin level was found to be a possible predictive marker of both a severe drop of Hb in the early phase of treatment and dose reduction of ribavirin.     

Absorption and excretion of ascorbic acid alone and in acerola (Malpighia emarginata) juice: comparison in healthy Japanese subjects

It has been suggested that some food components, such as bioflavonoids, affect the bioavailability of ascorbic acid in humans. Since little is known in Japan about the effective intake of this dietary requirement, we tested young Japanese males after the ingestion of commercial ascorbic acid or acerola (Malpighia emarginata DC.) juice to compare the quantities absorbed and excreted. Healthy Japanese subjects received a single oral dose of ascorbic acid solution (50, 100, 200 or 500 mg) and received distilled water as a reference at intervals of 14 d or longer. All subjects were collected blood and urine until 6 h after ingestion and evaluated for time-dependent changes in plasma and urinary ascorbic acid levels. Predictably, the area under the curve (AUC) values in plasma and urine after ingestion increased dose-dependently. Next, each subject received diluted acerola juice containing 50 mg ascorbic acid. Likewise, their plasma and urinary ascorbic acid concentrations were measured. In plasma, the AUC value of ascorbic acid after ingestion of acerola juice tended to be higher than that from ascorbic acid alone. In contrast, the urinary excretion of ascorbic acid at 1, 2 and 5 h after ingestion of acerola juice were significantly less than that of ascorbic acid. These results indicate that some component of acerola juice favorably affected the absorption and excretion of ascorbic acid.     

Uric Acid Levels in Tissues and Plasma of Mice during Aging

Here we quantified the uric acid (UA) levels in 11 tissues and plasma of C57BL/6 male mice to track its turnover during 3 to 30 months of aging. UA levels in the adrenal glands, heart, and spleen increased with aging until 30 months of age. Similarly, UA levels in the liver, kidneys, pancreas, and testes increased until the mice were 24 months old. UA levels also rose in the lungs and skeletal muscles from 3 to 6 months and 6 to 12 months, respectively, and then remained at almost the same levels until 30 months of age. In the skin, UA decreased from 3 to 6 months and then stayed nearly constant until 30 months of age. Moreover, the small intestines and plasma had quite stable UA levels during aging. Thus, our assessment of 11 tissue types from mice showed that the UA levels increased in most tissues during aging.     

Usefulness of serum S100B as a marker for the acute phase of aquaporin-4 autoimmune syndrome

The aquaporin-4 (AQP4) water channel antibody is used in the diagnosis of neuromyelitis optica (NMO) due to its high sensitivity and high specificity. However, some patients are reported to have neither optic neuritis nor myelitis despite being positive for the AQP4-autoantibody (AQP4-Ab). Therefore, recent reports suggest that such patients should be diagnosed as having 'AQP4-autoimmune syndrome'. In this study, we quantified the levels of glial fibrillar acidic protein (GFAP) and S100B by enzyme-linked immunosorbent assay (ELISA) in CSF and serum samples simultaneously obtained in the acute phase of ten AQP4-autoantibody (AQP4Ab)-positive and seven AQP4Ab-negative patients. Serum levels of S100B were significantly higher in the acute phase of the AQP4Ab-positive patients (2.92±1.22pg/ml) than in the AQP4Ab-negative patients (0.559±0.180pg/ml, p=0.0250), while serum levels of GFAP were not different between the two groups (AQP4Ab-positive vs. AQP4Ab-negative: 0.120±0.113ng/ml vs. 0.00609±0.00609ng/ml, p=0.193). Furthermore, the CSF and serum levels of S100B had a significant positive correlation in AQP4Ab-positive patients (n=10, r=0.673, p=0.0390). Our results raise the possibility that serum levels of S100B, but not GFAP, examined in the acute phase of the disease might be a useful biomarker for the relapse of AQP4 autoimmune syndrome.     

Association with 5'-untranslated region and response to interferon in chronic hepatitis C

BACKGROUND/AIMS: The 5'-untranslated region (5'UTR) of hepatitis C virus (HCV) is a useful region for determinations of genotype and viral load. 5'UTR can be used for simultaneous analysis of HCV genotype and viral load, therefore several assays have been described. A method which used direct sequencing of the 5'UTR can also be used to identify mutations in this region. The objective of the present study was to evaluate possible associations of 5'UTR mutations with responsiveness to interferon (IFN) therapy in chronic hepatitis C patients. METHODOLOGY: Seventy patients with chronic hepatitis C were included in this study. The relations between responsiveness to IFN therapy and HCV genotype, viral load, and 5'UTR mutations before IFN treatment were evaluated. RESULTS: We detected HCV genotype 1a (n = 5), 1b (n = 32), 2a (n = 15), 2b (n = 12), and 3a (n = 6). Forty-eight patients were non-sustained responders (NR). Seven of 37 (18.9%) patients with the 1a or 1b genotype were sustained responders (SR), and 14 of 27 (51.9%) patients with genotype 2a or 2b were SR. Responses of patients with genotype 1 were poorer than those of patients with genotype 2. HCV viral loads of all SR patients infected with genotype la or 1b were less than 100 KIU/mL, but more than 50% of SR patients infected with genotype 2a or 2b had viral loads over 100 KIU/mL. Thus, viral load in patients with genotype 1 is strongly associated with IFN sensitivity. 5'UTR were well conserved, and there were no differences in the distribution of genotypes between SR and NR. CONCLUSIONS: The 5'UTR is a suitable region for determining HCV genotype and viral load, which are predictors of responsiveness to IFN therapy, but specific mutations of the 5'UTR do not appear to be associated with responsiveness to IFN.     

Detection of the gonadal veins in the diagnosis of transposed ovaries in patients with cervical carcinoma: a useful sign on MDCT

OBJECTIVE: The purpose of our study was to evaluate the detectability of the gonadal vein of transposed ovaries in patients with uterine cervical cancer on MDCT. CONCLUSION: Gonadal veins and surgical clips of transposed ovaries can be shown with high consistency on MDCT. Tracking the gonadal veins and detecting the surgical clips may prevent the transposed ovaries from being misinterpreted as peritoneal implants.