Vitamin K2 Has No Preventive Effect on Recurrence of Hepatocellular Carcinoma after Effective Treatment

Hepatocellular carcinoma (HCC) has a poor prognosis because of its high recurrence rate. Recently, vitamin K2 has been reported to inhibit the growth of HCC cell lines. To clarify the preventive effect of vitamin K2 on HCC recurrence, we studied 72 HCC patients who had been treated with surgical resection, local ablation or transarterial embolization: their etiologies were hepatitis B virus (n = 21), hepatitis C virus (n = 47), both B and C viruses (n = 2) and non-B or non-C virus (n = 2). We divided them into 2 groups: in one group, patients were treated with 45-mg/day vitamin K2 [K2-treated group (n = 23)], and in another, patients were not given vitamin K2 or a placebo [non-treated control group (n = 49)]. The obtained results between the 2 groups were compared. HCC recurred in 12 (52.2%) of the 23 K2-treated patients, and 22 (44.9%) of the 49 control patients. The differences in cumulative recurrence-free rate and cumulative survival rate between both groups were not significant (P = 0.92 and P = 0.08, respectively). As observed, chemopreventive effects of vitamin K2 at a clinically relevant dose on HCC recurrence were ineffective after effective treatment for HCC. Different regimens such as higher doses of vitamin K2 or combination therapy with other drugs may be worth testing to further explore the preventive effect on HCC recurrence

α-Fetoprotein Messenger RNA in the Blood Predicts Poor Prognosis of the Patients with Hepatocellular Carcinoma

α-Fetoprotein (AFP) messenger RNA (mRNA) in the peripheral blood of patients with hepatocellular carcinoma (HCC) may indicate hematogenous spread of HCC. This study examined the presence of AFP mRNA in the blood of 148 patients, in terms of clinical parameters, tumor metastasis and survival rate. For the prospective study, 109 patients with HCC were followed in the period between March 1996 and March 1999. AFP mRNA in the blood was examined by means of nested reverse transcription polymerase chain reaction. AFP mRNA was detected in the blood in 23 (15.5%) of 148 patients with HCC. AFP mRNA in the blood was significantly correlated with protein induced by vitamin K absence or antagonist II level, higher AFP level (200 IU/mL or more) and extrahepatic metastases, but not with tumor size, number of tumor nodules or tumor-nodule-metastasis stage. This prospective study confirmed that intra- and extra-hepatic metastases developed more frequently in the 22 AFP mRNA-positive patients than in the 87 AFP mRNA-negative patients (P < 0.01). The cumulative survival rate was significantly lower in the former than in the latter (P < 0.01). In conclusion, AFP mRNA in the blood is closely related to hematogenous spread and might be a good predictor of metastasis and poorer survival rate in HCC patients

Effects of Endothelin-1 and Angiotensin-II on Extracellular Matrix Metabolism in a Rat Mesangial Cell Line, CRL-2573

The profibrogenic role of endothelin-1 (ET-1) and angiotensin-II (AT-II) in renal fibrosis remains disputed. We therefore studied the effect of ET-1 and AT-II on rat mesangial cells (CRL-2573), the major source of extracellular matrix proteins in the kidney. ET-1 stimulated DNA synthesis assessed by BrdU uptake in microtiter tetrazolium assay in a dose dependent manner, but AT-II did not. Proliferation of the mesangial cells by ET-1 was suppressed by 15% with BQ123, an endothelin receptor A antagonist, which suggested a significant role of the endothelin receptor A on growth stimulation. In the mesangial cells, ET-1 increased the mRNA expressions of procollagen α1 (I), transforming growth factor-β1, connective tissue growth factor, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-13 in dose dependent manners, whereas AT-II had exerted no effect on the expression of these mRNAs. These data suggested that ET-1 might be involved in renal fibrosis through the mesangial cell proliferation and/or the increase in fibrogenic cytokines

Small Bowel Obstruction Due to Mochi (Rice Cake): A Case Report and Review of the Literature

A 66-year-old man presented at our emergency department with severe intermittent abdominal pain. His history revealed that he had eaten several mochi (rice cakes) without sufficiently chewing them before swallowing. Following computed tomography that showed a high value, he was diagnosed with an obstruction caused by mochi. Although mochi obstruction can sometimes improve with conservative treatment, this case required laparotomy. Medical literature in English on small bowel obstruction due to mochi is rare, but fortunately in this case we were able to collect complete laboratory and imaging data. Furthermore, due to the surgical findings, we could clearly diagnose the pathophysiology of mochi obstruction. Here we describe a case of small bowel obstruction due to mochi, and review the literature to determine the characteristics of intestinal obstruction caused by it

Ipragliflozin Ameliorates Endoplasmic Reticulum Stress and Apoptosis through Preventing Ectopic Lipid Deposition in Renal Tubules

Background: Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health burdens closely related to metabolic syndrome. A link between CKD and NASH has been assumed; however, the underlying mechanism is still unknown. Ectopic lipid deposition (ELD) in the hepatocyte results in endoplasmic reticulum (ER) stress, which plays an important role in the development of steatohepatitis. ELD is also assumed to play a role in the development of kidney injury. We aimed to investigate the role of ELD and ER stress in the development of CKD, and evaluate the efficacy of a sodium glucose cotransporter-2 inhibitor, ipragliflozin. Methods: Male FLS-ob/ob mice that closely imitate the pathophysiology of NASH were treated with vehicle or ipragliflozin. Metabolic characteristics, histology of the kidney, ER stress, and apoptotic signals were evaluated. Results: The serum triglyceride was significantly lower in mice treated with ipragliflozin. Ipragliflozin reduced ELD in renal tubules. Ipragliflozin also reduced the expression levels of GRP78 and CHOP, apoptotic cells, and interstitial fibrosis. Conclusions: ELD induced kidney injury through ER stress. Ipragliflozin improved the pathogenesis of CKD by reducing ELD and ER stress in NASH-model mice. Our results suggest ipragliflozin has therapeutic effect on CKD in NASH

Renal shear wave velocity by acoustic radiation force impulse did not reflect advanced renal impairment

[Aim] Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end‐stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors. [Methods] Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non‐CKD group), and 39 end‐stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared. [Results] Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non‐CKD group and in the ESRD group, and no difference was found between the non‐CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non‐CKD group and the ESRD group, even when ages were matched and depth was adjusted. [Conclusion] Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages