Decreased expression of interferon-stimulated genes in B cells of patients with chronic hepatitis C during interferon-free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study.

AIMS: Hepatitis C virus (HCV) infection is monitored by the host innate immunity that includes the endogenous interferon (IFN), which up-regulates IFN-stimulated genes (ISGs). HCV is both hepatotropic and lymphotropic, but HCV replication in lymphoid cells is a controversial issue. Here, we analyzed the mRNA levels of the ISGs in B cells of HCV-infected patients during antiviral therapy and investigated the effects of viral eradication. METHODS: One hundred and eighty-one patients with chronic hepatitis C and 26 healthy volunteers were enrolled in this study. Levels of HCV RNA and mRNA of ISGs in B cells isolated from the patients were monitored before, during, and after antiviral therapy. RESULTS: HCV RNA was detected in B cells of 133/175 (76.0%) patients who achieved sustained virologic response (SVR) before therapy was started. The positive ratio of HCV RNA in B cells was higher in patients with genotype 1 and the non-major genotype of interleukin 28B. HCV RNA in B cells of most patients disappeared 1 week after antiviral therapy was started. The baseline expression of ISG mRNA was significantly higher in the patients than in the healthy volunteers. Levels of ISG mRNA were increased and remained high throughout the IFN-based therapy. In contrast, levels of ISG mRNA in patients who achieved SVR were significantly decreased 1 week after the IFN-free therapy was started and remained low during the therapy. CONCLUSIONS: These results suggested that IFN-free therapy potentially eradicated HCV in the B cells, leading to the down-regulation of endogenous ISGs. The level of ISG mRNA could be used as a marker for viral eradication in B cells.

Evaluation of the characteristics of the neutron beam of a linac-based neutron source for boron neutron capture therapy.

The linac-base neutron source "iBNCT" developed by the Tsukuba team has begun to generate a large intensity of neutrons. To confirm the applicability of the device to BNCT, several characteristic measurements have been implemented. In a water phantom experiment, when the accelerator was operated with an average current of 1.4 mA, the maximum thermal neutron flux was approximately 7.8 × 108 (n/cm2/s). Results demonstrate the stability of the linac over time, showing its promising potential for future patient treatment.

Three cases of histologically proven hepatic epithelioid hemangioendothelioma evaluated using a second-generation microbubble contrast medium in ultrasonography: case reports.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is rare; it is reported in < 1 person in 1,000,000 individuals. For accurate diagnosis, information regarding multiple graphic modalities in HEH is required. However, there is very little information concerning Sonazoid® contrast enhanced ultrasonography (CEUS) in HEH. CASE PRESENTATION: The present report describes the histologically proven three HEH cases evaluated using Sonazoid® CEUS. Case 1 was a 33-year-old female patient with no relevant past medical history, who experienced right upper quadrant pain. Conventional abdominal US revealed multiple low echoic liver nodules with vague borderlines. In CEUS, the vascularity of the nodules was similar to that seen in the neighboring normal liver. Later in the portal venous and late phases (PVLP) and post vascular phase, washout of Sonazoid® was detected in the nodules. Case 2 was a 93-year-old female patient with a previous medical history including operations for breast cancer and ovary cancer in her 50's. Conventional abdominal US revealed multiple low echoic nodules, some of which contained cystic lesions. In the early vascular phase of CEUS, nodules excluding the central anechoic regions were enhanced from peripheral sites. Although the enhancement inside the nodules persisted in both the PVLP and post vascular phase, anechoic areas in the center of some nodules were not enhanced at all. Case 3 was a 39-year-old male patient presented with right upper-quadrant pain, without any relevant past medical history. Conventional abdominal US revealed multiple low echoic liver nodules. In the early vascular phase of CEUS, nodules were gradually enhanced from the peripheral sites as ringed enhancement. Sonazoid®was washed out from the nodules in the PVLP and post vascular phase. CONCLUSIONS: The most important feature was peripheral enhancement in the early vascular phase. In case 2, the enhancement of the parenchyma of liver nodules persisted even in the PVLP; indicating the lower degree of malignant potential than others. Actually, the tumors did not extend without any treatment in case 2. Since case 2 is the first case report of HEH with cystic lesions, in patients with liver nodules including cystic lesions, HEH is a potential diagnosis.

[A case of rectal villous adenoma with electrolyte depletion syndrome treated with surgical resection].

A 65-year-old man was previously admitted to our university hospital thrice in the last 2 years because of acute kidney failure. This time he was admitted because of frequent diarrhea, anorexia, exacerbation of renal function, and hyponatremia. Rectal wall thickening was detected on computed tomography. Subsequently, a rectal polyp with mucous secretion was found on colonoscopy, which was further diagnosed as a subcutaneous villous adenoma on biopsy. Thus, electrolyte depletion syndrome associated with the rectal polyp was thought to be the cause of his symptoms. Finally, the patient underwent abdominoperineal resection of the rectum. Histopathologically, the rectal lesion was diagnosed as a villous/tubularadenoma without malignancy, and this is such a rare case to be reported.

Development of beryllium-based neutron target system with three-layer structure for accelerator-based neutron source for boron neutron capture therapy.

The iBNCT project team with University of Tsukuba is developing an accelerator-based neutron source. Regarding neutron target material, our project has applied beryllium. To deal with large heat load and blistering of the target system, we developed a three-layer structure for the target system that includes a blistering mitigation material between the beryllium used as the neutron generator and the copper heat sink. The three materials were bonded through diffusion bonding using a hot isostatic pressing method. Based on several verifications, our project chose palladium as the intermediate layer. A prototype of the neutron target system was produced. We will verify that sufficient neutrons for BNCT treatment are generated by the device in the near future.

[Establishing indicators for diagnosis of cholinergic crisis].

Cholinergic crisis is an adverse effect of an anticholinesterase agent, which is one of the cholinergic agents. Cholinergic crisis may induce serious conditions such as breathing difficulties. Cholinergic crisis is often diagnosed by an abnormally low level of serum cholinesterase (ChE). However, ChE value is not an appropriate indicator of cholinergic crisis since it has a high inter-individual variation, even though its intra-individual variation is low. Therefore, an indicator with less inter-individual variation capable of preventing the risk of cholinergic crisis was investigated. The results of correlation test between ChE and serum albumin (Alb) showed a strong positive correlation; r = 0.778 in BCG method(Bromo cresol green method) and r = 0.766 in the BCP-improved method for Alb. In addition, the variations of Alb values are much lower than the drastic depression of ChE values in cholinergic crisis. Thus, it is considered that the ratio of ChE and Alb (ChE/Alb) can be a useful indicator of cholinergic crisis. As a result of ROC (Receiver operating characteristic) analysis, the ratios of ChE and Alb values using the BCG method (ChE/Alb (BCG)) were 20.7, 87.0, 156.8 for the Cutoff value, Likelihood ratio and Odds ratio respectively. When using the BCP-improved method for Alb, the ratios of ChE and Alb (ChE/Alb(BCP improved)) were 25.0, 93.7, 180.1 for the Cutoff value, Likelihood ratio and Odds ratio respectively. The ChE/Alb ratio appears to be an excellent indicator of cholinergic crisis diagnosis since it shows a high likelihood ratio as well as a high odds ratio.

[Case of submucosal esophageal carcinoma with multiple liver metastasis showing high serum levels of CEA and CA19-9].

A 57-year-old man was admitted because of abdominal fullness. An abdominal ultrasonographic study disclosed multiple space-occupying lesions (SOL) in the liver. On blood examinationC the serum levels of CEA and CA19-9 were significantly high while those of AFP and SCC were within normal ranges. Endoscopically biopsied specimens of the lower esophagus histologically revealed poorly differentiated squamous cell carcinoma. Pathohistologically similar findings were obtained from the needle biopsied specimen of the SOL in the liver. Thus the patient was diagnosed as having squamous cell carcinoma of the esophagus with liver metastasis. On the 41st hospital day the patient died and an autopsy was performed. Although multiple metastases were recognized, cancer cells were limited within the submucosa of the esophagus. Immunostaining of CEA and CA19-9 was positive on the carcinoma cells both in the esophagus and the liver. Thus a relation between the biological malignancy of esophageal cancer and serum levels of CEA and CA19-9 was suggested.

Development of hepatocellular carcinoma following treatment with 6-mercaptopurine for ulcerative colitis: investigation of chromosomal aberration by comparative genomic hybridization.

In a 64-year-old man who had been treated with prednisolone (PSL) and 6-mercaptopurine (6MP) for a long period, for ulcerative colitis (UC), hepatocellular carcinoma (HCC) was detected incidentally. The UC was in remission with these medications. After he had been taking these medications for about 8 years, HCC was detected by computed tomography (CT), done for the evaluation of an other disease. Blood chemistry examination results were normal, except that the protein induced by vitamin K antagonist (PIVKA)-II level was 7940 AU/ml. We performed resection of liver segment V. With comparative genomic hybridization, chromosomal aberrations were recognized; these were gains of 1q, 3ptel-21, 8p12, and 22q11.23-22q13.1. Generally, HCC is associated with hepatitis virus infection in most cases, but in this patient, the HCC was not related to hepatitis C virus (HCV) or HBV. It is presumed that this case was related to the immunosuppressive therapy for UC and was associated with the gains of 1q, 3p, and 8p.