Radiofrequency Echographic Multispectrometry (REMS) can Overcome the Effects of Structural Internal Artifacts and Evaluate Bone Fragility Accurately.

PURPOSE: This study measured bone mineral density (BMD) in a Japanese population using the novel non-ionizing system using radiofrequency echographic multispectrometry (REMS) and compared the results with those obtained using traditional dual-energy X-ray absorptiometry (DXA). We aimed to identify any discrepancies between measurements obtained using these instruments and identify the influencing factors. METHODS: This cross-sectional study examined patients with osteoporosis treated at a single center from April to August 2023. We examined BMD assessment by DXA and REMS in lumbar spine and proximal femur. Patients were categorized into two groups: those with discrepancies between lumbar spine BMD measured by DXA and REMS, and those without. Semiquantitative evaluation of vertebral fractures and abdominal aortic calcification scoring were also performed and compared between the two groups, along with various patient characteristics. RESULTS: A total of 70 patients (88.6% female; mean age 78.39 ± 9.50 years) undergoing osteoporosis treatment were included in the study. A significant difference was noted between DXA and REMS measurement of BMD and T-scores, with REMS recording consistently lower values. The discrepancy group exhibited a higher incidence of multiple vertebral fractures and increased vascular calcification than the non-discrepancy group. Multivariate analysis indicated that diabetes mellitus, severe vertebral fractures, and increased abdominal aortic calcification scores were significantly associated with discrepancies in lumbar spine T-scores. CONCLUSION: This study suggests that REMS may offer a more accurate measurement of BMD, overcoming the overestimation of BMD by DXA owing to factors such as vertebral deformities, abdominal aortic calcification, and diabetes mellitus.

Hypomobility in Males and Hypermobility in Females are Risk Factors for Shoulder Pain Among Young Swimmers.

CONTEXT: The range of shoulder rotation is associated with shoulder pain in young male and female swimmers. However, the association between shoulder pain and shoulder complex mobility of the scapulothoracic and acromioclavicular joints has not yet been examined. Moreover, shoulder pain occurs more frequently in females than in males, but only a few studies have examined the relationship between shoulder pain and sex as a risk factor. This study aims to determine the association between shoulder complex mobility and shoulder pain in young male and female swimmers. DESIGN: Prospective cohort design. METHODS: The participants were competitive swimmers (n = 76; 37 males and 39 females) with a mean age of 14 years in Japan. The shoulder rotation width, which was the index of shoulder complex mobility, shoulder internal and external rotation range, and middle finger distance of the back-scratch test were measured. An examiner regularly visited the swimming clubs to evaluate the development of shoulder pain and swimming distance. Logistic regression analysis was used to determine the physical characteristics related to the overall development of shoulder pain in both female and male swimmers. The cutoff value was calculated using receiver operating characteristic curves. RESULTS: Sixteen participants, composed of 8 males and 8 females, developed shoulder pain. The overall swimming distance of the male (odds ratio [OR]: 1.0007, P = .01) and female (OR: 1.0018, P = .02) swimmers and the shoulder rotation width of the male (OR: 1.0952, P = .04) and female (OR: 0.888, P = .03) swimmers were identified as risk factors for shoulder pain. The cutoff value for swimming distance was 6000 m. Shoulder rotation width was more than 88 cm in males and <54 cm in females. CONCLUSIONS: Hypomobility and hypermobility of the shoulder complex were identified as risk factors for shoulder pain in male and female swimmers, respectively.

Interobserver size measurement variability in part-solid lung adenocarcinoma using pre-operative computed tomography.

BACKGROUND: In the current lung cancer tumor-node-metastasis classification, solid tumor size is used for tumor diameter measurement as the dense component. However, measuring solid tumor size is sometimes difficult and inter-observer variability may increase, particularly in part-solid nodules with ground-glass opacity (GGO). This study aimed to investigate inter-observer size measurement variability in lung adenocarcinoma. METHODS: Of 47 patients with part-solid lung adenocarcinoma who had undergone surgery at our department from January to December 2016, five surgeons and one radiologist undertook unidimensional solid and total size tumor measurements using pre-operative axial computed tomography images, and we assessed inter-observer size measurement variability. Variability was then subclassified into five groups, according to computer tomography-identified tumor morphological characteristics, namely: (I) minimally invasive; (II) peribronchovascular; (III) spiculation/atelectasis; (IV) adjacent to cystic lesion, and; (V) diffuse consolidation and GGO. RESULTS: The mean inter-observer variability was 9.7 mm (solid size) and 7.7 mm (total size). Analysis of the maximum and minimum measurement size values for each patient undertaken showed that the most experienced surgeon and the radiologist measured the minimum size more frequently. To correct for differences in mean tumor diameter in each group, a comparison was made using a coefficient of variation (CV) calculated as the ratio of the standard deviation to the mean. Group I characteristics showed the largest coefficient value for variation in solid size measurement. CONCLUSIONS: Inter-observer measurement variability for solid size was larger than for total size in lung adenocarcinoma. Large variability in group I indicated the difficulty of size measurement for low-grade malignant potential nodules such as adenocarcinoma in situ, minimally invasive adenocarcinoma, and early-stage invasive adenocarcinoma. The possibility of unavoidable size measurement variability should be recognized when deciding on surgical procedures for these diseases.

Triterpene Glycosides from the Seeds of Dolichos lablab.

Two new triterpene glycosides (1 and 2), together with nine known triterpene glycosides (3-11), were isolated from the seeds of Dolichos lablab (Leguminosae). The structures of the new compounds were determined by spectroscopic analysis, including two-dimensional NMR spectroscopy, and chromatographic analysis of the hydrolyzed products. The isolated compounds did not show cytotoxicity against HL-60 human leukemia cells and HepG2 human hepatoma cells at sample concentrations of 20 µM.

Mixed HCV Infection of Genotype 1B and Other Genotypes Influences Non-response during Daclatasvir + Asunaprevir Combination Therapy.

Daclatasvir (DCV) + asunaprevir (ASV) combination therapy has become available for patients with hepatitis C virus (HCV) serogroup 1 infection. We studied the efficacy of this therapy by focusing on the factors associated with sustained virological responses (SVR) including resistance-associated variants (RAVs) and mixed infection of different HCV genotypes. We enrolled 951 HCV serogroup 1-positive patients who received this combination therapy at our hospital or affiliated hospitals. The presence of RAVs in non-structural (NS) regions 3 and 5A was analyzed by direct sequencing. HCV genotypes were determined by PCR with genotype-specific primers targeting HCV core and NS5B regions. SVR was achieved in 91.1% of patients. Female sex, age > 70 years, and RAVs were significantly associated with non-SVR (p<0.01 for all). Propensity score-matching results among the patients without RAVs regarding sex, age, and fibrosis revealed that mixed HCV infection determined by HCV NS5B genotyping showed significantly lower SVR rates than 1B-mono infection (p=0.02). Female sex and RAVs were significant factors associated with treatment failure of this combination therapy for patients with HCV serogroup 1 infection. Mixed HCV infection other than 1B-mono infection would be useful for predicting treatment failure.

Entecavir Reduces Hepatocarcinogenesis in Chronic Hepatitis B Patients.

Chronic hepatitis B (CHB) leads to cirrhosis and hepatocellular carcinoma (HCC). With a cohort of 1,206 CHB patients who visited Okayama University Hospital and related hospitals in 2011 and 2012, we compared the incidence rates of HCC among the patients grouped by age, hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), and treatment. HCCs were observed in 115 patients with the median observation period of 1,687 days. Among the HCC patients aged > 35 years, HBV DNA > 4 log copies/mL and positive HBeAg at diagnosis (n＝184), the HCC incidence rate was 8.4% at 5 years in the entecavir (ETV)-treated patients, 21.8% in the lamivudine (LVD)-treated patients, and 26.4% among the patients not treated with drugs. The cumulative HCC incidence was significantly reduced in the ETV-treated patients compared to those treated with LVD or not treated (p＝0.013). Among the patients aged >35 years with HBV DNA > 4 log copies/mL and negative HBeAg (n＝237), the cumulative HCC incidence was 14.6% in 5 years in ETV group and 13.9% among those not treated with a drug (p＞0.05). Only small numbers of HCCs occurred in other patients. In CHB patients aged > 35 years with HBV DNA > 4 log copies/mL and positive HBeAg, ETV treatment is recommended for the suppression of HCC development.

Reactivation of hepatitis B virus during interferon-free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co-infection.

Direct-acting antiviral agents (DAA) for hepatitis C virus (HCV) are not effective for hepatitis B virus (HBV), which may be suggestive of reactivation of anti-HBe hepatitis during interferon (IFN)-free DAA therapy in HBV/HCV co-infected patients with inactive HBV. A 69-year-old male patient was diagnosed with chronic hepatitis due to HBV/HCV co-infection with serum levels of alanine aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log copies/mL. HCV was thought to be responsible for the hepatitis activity because of low level of HBV core-related antigen (3.1 log U/mL). He was treated with combination therapy of daclatasvir and asunaprevir. Serum ALT gradually increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was stopped due to suspicion of drug-induced liver injury and/or HBV reactivation. Administration of entecavir reduced HBV DNA levels, followed by improvement in ALT levels. This report proposes that close monitoring of HBV DNA during the anti-HCV DAA therapy and the commencement of anti-HBV therapy with nucleoside analogs after the increase of HBV DNA should be considered in patients with HBV/HCV co-infection.

Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development.

AIM: To investigate factors that accurately predict hepatocellular carcinoma (HCC) development after antiviral therapy in chronic hepatitis C (CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein (AFP) to predict HCC development after interferon (IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response (SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/mL before therapy and in non-SVR patients showing AFP ≥ 5 ng/mL before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/mL before therapy and no decrease in AFP to < 5 ng/mL 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/mL before therapy and decreased AFP (P = 0.043). AFP ≥ 5 ng/mL before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase (ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/mL before therapy than in those showing AFP ≥ 5 ng/mL. CONCLUSION: The criteria of AFP < 5 ng/mL before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

Prevalence and outcomes of acute hepatitis B in Okayama, Japan, 2006-2010.

Hepatitis B virus (HBV) is one of the major viruses causing acute hepatitis. Recently, the incidence of acute hepatitis with genotype A has been increasing in Japan. The aim of this study was to investigate acute hepatitis B (AHB) in Okayama prefecture, with special attention to HBV genotype A. AHB patients who visited one of 12 general hospitals in Okayama prefecture between 2006 and 2010 were retrospectively analyzed. Over the course of the study period, 128 patients were diagnosed with AHB. Sexual transmission was supposed in the majority of patients (78 patients, 61%), including 59 (76%) having sex with heterosexual partners. The genotypes of HBV were assessed in 90 patients (70%), of whom 27 patients were infected with genotype A, 5 with genotype B, and 58 with genotype C. The prevalence of genotype A was significantly higher among male patients (28.7%), aged 20-29 (35.6%, p＜0.01), among men who had sex with men (100%, p＜0.005), and among patients having sex with unspecified partners (44.8%, p＜0.005). Genotype A was not a significant factor associated with delayed HBsAg disappearance. Caution should be exercised with regard to sexually transmissible diseases in order to slow the pandemic spread of AHB due to genotype A.

[The impact of guidelines for the management of acute cholecystitis in a rural area of Japan].

We monitored the management of acute cholecystitis in a rural area of Japan to determine the effectiveness of new guidelines for the management of acute cholecystitis and cholangitis. Between January 2000 and September 2011, 366 patients were treated for acute cholecystitis. Of these, 59 had common bile duct stones (CBDS) and 307 did not. Patients in both groups were further subdivided into two groups: a before guidelines group (BGG; n=153) and an after guideline group (AGG; n=154). Among the patients without CBDS, early cholecystectomy was more common in the AGG group (n=53) than in the BGG group. Furthermore, the length of hospital stay was four days shorter in the AGG group than in the BGG group (n=23). Among the patients with CBDS, the timing of cholecystectomy after endoscopic retrograde cholangiography was seven days earlier in the AGG group than in the BGG group. Even in a rural area of Japan, early cholecystectomy appears safe and can decrease the length of hospital stay.

The diagnosis of hypovascular hepatic lesions showing hypo-intensity in the hepatobiliary phase of Gd-EOB- DTPA-enhanced MR imaging in high-risk patients for hepatocellular carcinoma.

The aim of this study was to evaluate the histologic diagnosis of hypovascular hepatic lesions showing hypointensity on hepatobiliary phase images of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI (EOB-MRI). In 38 patients with hepatocellular carcinoma (HCC) after curative treatments and 18 patients with liver cirrhosis, 105 hypovascular nodules that were hypointense at the hepatobiliary phase of EOB-MRI were biopsied and the clinical usefulness of these EOB-MRI findings for the diagnosis of HCC was examined. Of the 105 nodules (median diameter = 12mm), 78 (74.3%), 11 (10.5%), and 16 (15.2%) were diagnosed as HCC, dysplastic, and non-neoplastic, respectively. The positive predictive value (PPV) of hypointensity at the hepatobiliary phase of EOB-MRI for the diagnosis of HCC increased to 77-90% when combined with the following factors: washout appearance on the delayed phase of triple-phase CT, hyperintensity in diffusion-weighted image of MRI, or the appearance of a hypoechoic part in ultrasonography. PPV increased to 100% when all 3 factors were positive. A relatively large proportion of hypovascular lesions that showed hypo-intensity in the hepatobiliary phase were confirmed to be HCC, and the accuracy of HCC increased when combined with other imaging findings.

Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein.

BACKGROUND AND AIM: Fucosylated alpha-fetoprotein (AFP-L3) is known to be a marker of poor prognosis in patients with hepatocellular carcinoma (HCC). However, it has been difficult to measure AFP-L3 under low AFP (≤ 20 ng/mL). The aim of this study was to elucidate the role of AFP-L3 in HCC patients with low AFP conditions. METHODS: One hundred and ninety six consecutive newly developed HCC patients with low AFP (≤ 20 ng/mL) were examined for serum AFP-L3 expression by a newly-developed micro-total analysis system that could stably measure AFP-L3 in low AFP circumstances, and its clinical importance was analyzed. RESULTS: Positivity of AFP-L3 in HCC patients was 13.3% at a cut-off level of 10%. Five-year survivals of HCC patients with AFP-L3 (< 10%) and AFP-L3 (≥ 10%) were 69.4% and 41.1%, respectively (P = 0.001). Among 18 clinical parameters, low alanine aminotransferase, large tumor size, presence of portal vein tumor thrombus, high AFP and high des-gamma carboxy prothrombin were observed in the high AFP-L3 (≥ 10%) group. Multivariate analysis revealed that high aspartate aminotransferase (AST) (risk ratio [RR]= 3.24, 95% confidence interval [CI] = 1.27-8.26), the presence of ascites (RR = 3.44, 95% CI = 1.22-9.34), multiple tumor number (RR= 3.06, 95% CI = 1.33-7.17), and high AFP-L3 (RR = 8.36, 95% CI= 2.79-25.5) were risk factors for survival. High AFP-L3 was also a risk factor for survival in HCC patients who received radiofrequency ablation (P = 0.048). CONCLUSIONS: AFP-L3 is a strong prognostic factor for survival even in HCC patients with low AFP (≤ 20 ng/mL).

Hepatocellular carcinoma occurring in hepatobiliary fibropolycystic disease.

Congenital hepatic fibrosis (CHF) and bile duct hamartomas (von Meyenburg complexes) are hepatobiliary fibropolycystic diseases. There have been several reports of liver neoplasias arising in hepatobiliary fibropolycystic diseases. However, most of them were cholangiocarcinomas and cases involving hepatocellular carcinoma (HCC) are rare. A 51-year-old woman was found to have multiple hepatic tumors by ultrasonography and enhanced computed tomography (CT) during a regular work-up for the recurrence of lung cancer and thyroid cancer, which had been surgically removed 4 and 3 years ago, respectively. Nodules were observed at S3, S5, and S6 (2 cm in diameter). All of the nodules were hyperattenuated at the early arterial phase, and the main tumor at S5 showed hypoattenuation at the delayed phase on dynamic CT and magnetic resonance imaging (MRI). HCC was suspected from these findings. She also suffered from multiple small cystic lesions in the liver. The surgically removed liver showed HCC arising in CHF, which is a rare histological finding.

Serum levels of platelet-derived growth factor-BB and vascular endothelial growth factor as prognostic factors for patients with fulminant hepatic failure.

BACKGROUND AND AIMS: In animal models for acute liver injury, the administration of some angiogenic factors such as vascular endothelial growth factor (VEGF) and granulocyte-colony stimulating factor (G-CSF) are shown to reduce liver injury and improve liver proliferative capacity. The aim of the present study was to assess the role of angiogenic factors in fulminant hepatic failure (FHF). METHODS: Serum levels of nine angiogenic factors (angiopoietin-2, follistatin, G-CSF, hepatocyte growth factor [HGF], interleukin-8, leptin, platelet-derived growth factor [PDGF]-BB, platelet endothelial cell adhesion molecule-1 and VEGF) were measured using the Bio-Plex Protein Array System in 30 patients, 17 of whom were diagnosed with FHF, 13 with acute hepatitis (AH), and 20 controls. RESULTS: Serum levels of PDGF-BB and VEGF were lower in FHF patients than AH patients and controls (PDGF-BB; 2050±1572 pg/mL vs 4521±2419 pg/mL vs 8506±5500 pg/mL, VEGF; 39±38 pg/mL vs 144±122 pg/mL vs 205±121 pg/mL). By using univariate logistic regression models, serum levels of PDGF-BB and VEGF were associated with poor outcomes. Serum PDGF-BB levels were strongly correlated with serum VEGF levels (r=0.70). Furthermore, serum PDGF-BB levels were significantly correlated with platelet counts (r=0.79), PT activity (r=0.37) and D.Bil/T.Bil ratio (r=0.50), while serum VEGF levels were significantly correlated with platelet counts (r=0.68) and PT activity (r=0.38). CONCLUSIONS: We consider that serum levels of PDGF-BB and VEGF are worth investigating as biomarkers for predicting outcomes of FHF patients.

Complete atrioventricular block secondary to lithium therapy.

Sinus node dysfunction has been reported most frequently among the adverse cardiovascular effects of lithium. In the present case, complete atrioventricular (AV) block with syncopal attacks developed secondary to lithium therapy, necessitating permanent pacemaker implantation. Serum lithium levels remained under or within the therapeutic range during the syncopal attacks. Lithium should be used with extreme caution, especially in patients with mild disturbance of AV conduction.

Duodenal duplication cyst of the ampulla of Vater.

A 35-year-old man presented with the complaint of epigastric discomfort. Gastrointestinal endoscopy and endoscopic ultrasonography revealed a cystic lesion 20 mm in size at the ampulla of Vater. Endoscopic retrograde cholangiopancreatography (ERCP) revealed that the cystic lesion communicated with both the common bile duct and pancreatic duct via the common channel. Choledochocele was ruled out by close examination of the ERCP findings. The cystic lesion was surgically resected. Since histological findings revealed that the mucosa inside the lesion was duodenum-like and contained a layer of smooth muscle, the lesion was diagnosed as a congenital duplication cyst of the duodenum.

Hepatic steatosis correlates with the postoperative recurrence of hepatitis C virus-associated hepatocellular carcinoma.

BACKGROUND: Hepatic steatosis is a prominent feature of chronic hepatitis C. Hepatic steatosis was reported recently to be a risk factor for hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). AIM: To investigate whether hepatic steatosis influences the postoperative recurrence of HCV-associated HCC. METHODS: A retrospective study was conducted in 88 patients undergoing curative resection of HCV-associated HCC. Cumulative tumour recurrence rates were compared between steatosis-positive and steatosis-negative patients, and the factors affecting intrahepatic recurrence were assessed. RESULTS: The respective tumour recurrence rates at 1, 3, and 5 years were 19%, 76%, and 92% in the steatosis-positive group, and 12%, 52%, and 60% in the steatosis-negative group. The tumour recurrence rate of the steatosis-positive group was significantly higher than that of the steatosis-negative group (P=0.02). Hepatic steatosis [relative risk (RR)=3.31, 95% confidence intervals (CIs)=1.49-7.41, P=0.003], stage of fibrosis (RR=3.17, 95% CI=1.35-7.47, P=0.008), surgical procedure (RR=0.22, 95% CI=0.076-0.64, P=0.005), number of tumours (RR=5.24, 95% CI=1.63-16.80, P=0.005), size of the largest tumour (RR=3.52, 95% CI=1.28-9.69, P=0.02), and vascular invasion (RR=2.72, 95% CI=1.32-5.59, P=0.007) were independent factors for tumour recurrence rate by multivariate analysis. CONCLUSIONS: Hepatic steatosis is a useful predictor of postoperative recurrence of HCV-related HCC.

Gastric ulcer after prophylactic balloon-occluded retrograde transvenous obliteration.

A 74-year-old man with compensated hepatitis C virus-related liver cirrhosis was admitted for the treatment of small hepatocellular carcinoma (HCC) by radiofrequency ablation therapy (RFA). As a routine pretreatment examination, gastrointestinal endoscopy was performed, and large nodular varices were observed in the gastric fornix, with telangiectasia on top of the varices. As soon as the RFA was completed, prophylactic balloon-occluded retrograde transvenous obliteration (B-RTO) was performed. Seven days after the B-RTO, the patient complicated of upper abdominal pain. Gastrointestinal endoscopy was performed, and a deep ulcer, located at the top of the tumor-shaped gastric varices, was found. The ulcer showed rapid healing after 1-week administration of a proton pump inhibitor (PPI). A severe ulcer after a B-RTO procedure, is extremely rare, because sclerosing agents rarely flow into the gastric mucosa. The ulcer in this patient was deep and large, and it may have been due to direct mucosal damage caused by the sclerosing agent, because mucosal telangiectasia on top of the varices was observed before the B-RTO. It is likely that, in this patient, the mucosal vessels communicated with the submucosal large varices, and ethanolamine oleate (EOI) flowed into the gastric mucosa via this communication. Based on our experience, we recommend periodic follow-up endoscopy.