Novel image analysis method using ultrasound elastography for noninvasive evaluation of hepatic fibrosis in patients with chronic hepatitis C.

It has been established that the long-term infection of chronic hepatitis C leads to the increased risk of hepatic fibrosis and hepatocellular carcinoma. Currently, histological diagnosis by invasive and painful liver biopsy is the gold standard for evaluating the hepatic fibrosis stage. Because of a side effect or patient inability to cope with the pain, it is difficult to assess the fibrosis stage frequently using liver biopsy. Recently, instead of liver biopsy, many articles have been published showing the usefulness of ultrasound elastography to evaluate the stage of hepatic fibrosis. We also reported the usefulness of real-time tissue elastography (RTE) for liver fibrosis staging in 2007. However, in our previous report, fibrosis classification was performed manually and the number of patients involved was also small. In the current study, the fibrosis staging is performed automatically using software by characterizing the elastography images. We have also increased the number of patients from 64 to 310. Thus, the aim of this study is to increase objectivity by using a newly developed automatic analysis method. We obtain the Liver Fibrosis Index (LFI), which is calculated from image features of RTE images, using multiple regression analysis performed on clinical data of 310 cases as the training data set. The correlation coefficient obtained between the LFI and the stage of hepatic fibrosis was r = 0.68, and significant differences exist between all stages of fibrosis (p < 0.001). Our new method seems promising since it has the ability to diagnose fibrosis even in the presence of inflammation.

Scraping cytology with a guidewire for pancreatic-ductal strictures.

BACKGROUND: Strictures of the pancreatic duct may be caused by a variety of underlying pathologic conditions that imaging examinations often fail to define. Conventional procedures for acquisition of a specimen for cytology during ERCP have been limited in their ability to discriminate pancreatic-ductal strictures. OBJECTIVE: Our aim was to discriminate pancreatic-ductal strictures by a new technique of sampling material for cytodiagnosis: scraping cytology with a guidewire. DESIGN: A retrospective study. SETTING: A single cancer center. PATIENTS AND METHODS: Eighty-six patients with pancreatic-ductal strictures composed of 71 malignant and 15 benign diseases were evaluated. Malignant diseases included 70 pancreatic carcinomas and 1 endocrine tumor; benign diseases included the following: 7 chronic pancreatitis, 3 autoimmune pancreatitis, 3 idiopathic pancreatic-ductal strictures, and 2 pancreatic cysts. During ERCP, pancreatic juice was collected with a cannula in the main duct just below the stricture after scraping it with a 0.025-inch hydrophilic guidewire. Cytodiagnosis of the specimen was performed by the Papanicolaou method. MAIN OUTCOME MEASUREMENTS: Diagnostic sensitivities and specificities of scraping cytology with a guidewire for pancreatic carcinoma. RESULTS: Scraping cytology with a guidewire yielded 93% sensitivity, 100% specificity, 100% positive predictive value, 75% negative predictive value, and 94% accuracy. Sensitivities for pancreatic carcinoma in the head, body, and tail of the pancreas were 91%, 100%, and 91%, respectively. Sensitivities for pancreatic carcinoma with a tumor of <20 mm, 21 to 40 mm, 41 to 60 mm, and >61 mm were 95%, 92%, 100%, and 100%, respectively. Pancreatitis subsequent to the procedure occurred in 4 patients (5%), all of whom were cured by conservative treatment. CONCLUSIONS: Benign or malignant pancreatic-ductal strictures were accurately discriminated by scraping cytology with a guidewire during ERCP. The technique yielded high diagnostic sensitivities in pancreatic carcinoma, regardless of the location or size of the tumor.

Contrast-enhanced multiphase dynamic ultrasonography for the characterization of liver tumors.

PURPOSE: The purpose of the study was to introduce our protocol for contrast-enhanced multiphase dynamic ultrasonography (US) and examine the effectiveness of this method for characterizing liver tumors. METHODS: The subjects were 142 patients with liver tumors. The final diagnoses were 58 hepatocellular carcinomas (HCCs), 4 cholangiocellular carcinomas (CCCs), 14 metastases, 29 hemangiomas, 6 cases of focal nodular hyperplasia (FNH), and 31 other benign lesions. The contrast agent used was Levovist. A wide-band pulse inversion harmonic imaging mode was employed. Multiphase dynamic US was achieved by changing the sound transmission interval automatically from 0.3 s to 15.0 s according to a preset menu. Early arterial-phase images were observed at the short interval, and an equilibrium-phase image was observed at the longest interval. After a series of vascular images, a postvascular liver parenchymal image was obtained. Based on previously published criteria, the most compatible diagnosis was noted. The accuracy of this multiphase dynamic US technique for diagnosing focal liver lesions was examined by comparing our results with the final diagnosis based on a prospective study. RESULTS: The overall accuracy of all 142 cases was 93.7%. The sensitivity, specificity, and positive predictive value were, respectively, 100%, 92.9%, and 90.6% for HCC; 88.9%, 97.6%, and 84.2% for metastasis or CCC; 89.7%, 100%, and 100% for hemangioma; and 83.3%, 100%, and 100% for FNH. CONCLUSION: Contrast-enhanced multiphase dynamic US is a highly accurate, safe diagnostic tool for characterizing liver tumors.

Osteopontin as a positive regulator in the osteoclastogenesis of arthritis.

We examined the role of osteopontin (OPN) in the osteoclastogenesis of arthritis using collagen-induced arthritis (CIA). Cells from arthritic joints of wild-type (OPN +/+) mice spontaneously developed bone-resorbing osteoclast-like cells (OCLs). The cultured cells showed an enhanced expression of receptor activator of nuclear factor kappaB ligand (RANKL) and a decreased expression of osteoprotegerin (OPG). The addition of OPG reduced the number of OCLs, indicating that the osteoclastogenesis depends on the RANK/RANKL/OPG system. The cells also produced OPN abundantly and anti-OPN neutralizing antibodies suppressed the development of OCLs. Moreover, the addition of OPN increased the expression of RANKL and augmented differentiation of OCLs from OPN-deficient (OPN -/-) cells. OPN, like the combination of 1alpha,25-dihydroxyvitamin D(3) and dexamethasone, also enhanced the RANKL expression and decreased OPG expression in a stromal cell line, ST2. These results suggest that OPN acts as a positive regulator in the osteoclastogenesis of arthritis through the RANK/RANKL/OPG system.

Prevention by bovine milk against Helicobacter pylori-associated atrophic gastritis through its adherence inhibition.

BACKGROUND/AIMS: The effects of Helicobacter pylori infection on the development of atrophic gastritis and intestinal metaplasia in relation to lifestyle and diet and the effect of the bovine milk on H. pylori adherence to gastric antral mucosa were investigated. METHODOLOGY: H. pylori infection was investigated in 63 patients without endoscopic evidence of gastroduodenal disease. Presence of H. pylori infection was assessed by culture and histologic examination of antral and corpus biopsy samples. Grades of atrophic gastritis and intestinal metaplasia were judged with chromoendoscopy (Congo red-methylene blue test). Adherence of H. pylori was evaluated with scanning electron microscopic examination of antral mucosa in Mongolian gerbils. RESULTS: Cross-sectional analysis of lifestyle and diet showed that a high intake of bovine milk was significantly related to prevention of H. pylori infection and the developments of atrophic gastritis and intestinal metaplasia. H. pylori adherence to the gastric mucosa was inhibited by bovine milk in a dose-dependent manner. CONCLUSIONS: Bovine milk prevents the development of atrophic gastritis and intestinal metaplasia through its defense mechanisms against the attachment of H. pylori to the gastric mucosa.

Enhanced production of osteopontin in multiple myeloma: clinical and pathogenic implications.

In this study, we examined osteopontin (OPN) production in myeloma cells and plasma OPN levels in multiple myeloma (MM) patients. We assessed OPN production in bone marrow cells (BMCs) by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA). We also assessed OPN production in various B-cell malignant cell lines, including three myeloma cell lines by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. In addition, we measured plasma OPN concentrations by ELISA in 30 MM patients, 21 monoclonal gammopathy of undetermined significance (MGUS) patients and 30 healthy volunteers. As a result, in an immunocytochemical study, abundant OPN was detected in BMCs from overt MM patients, whereas no OPN was detected in BMCs from patients with other haematological diseases, including MGUS. Cultured BMCs from overt MM patients produced more OPN than those from patients with either smouldering MM or MGUS. Myeloma cell lines spontaneously produced OPN. Plasma OPN levels of MM patients were significantly higher than those of MGUS patients and healthy volunteers (P < 0.05). Moreover, they correlated with both progression and bone destruction of the disease (P < 0.05). These suggest that myeloma cells actively produce OPN, which possibly contributes to osteoclastic bone resorption in MM. Plasma OPN levels may be a useful biomarker for assessing bone destruction in MM and distinguishing MM from MGUS or smouldering MM.