Evaluation of various imaging methods in the differential diagnosis of intraductal papillary-mucinous tumor (IPMT) of the pancreas

BACKGROUND/AIMS: IPMT (intraductal papillary-mucinous tumor) of the pancreas has unique clinicopathological characteristics. The lesions which show characteristic clinical features of IPMT exhibit a wide spectrum of histological types ranging from atypical hyperplasia to invasive cancer. Therefore, surgical treatment cannot be recommended for all patients with IPMT. It is necessary to assess the malignant potential of IPMT in individual patients in order to select an appropriate approach. The aim of this study was to evaluate the effectiveness of endoscopic ultrasonography and intraductal ultrasonography as compared with ultrasonography and computed tomography for this purpose. METHODOLOGY: Ultrasonography, computed tomography, endoscopic ultrasonography and intraductal ultrasonography were performed in 49 cases of IPMT (atypical hyperplasia 7, adenoma 23, noninvasive 7 and invasive adenocarcinoma 12). On the basis of the histopathological analysis of another 28 cases of resected IPMT specimens, criteria for differential diagnosis by imaging modalities were defined as follows: Nonneoplastic lesion (atypical hyperplasia): no wall thickening or nodule; noninvasive IPMT (adenoma and intraductal carcinoma): a nodule or wall thickening is present; and invasive IPMT with pancreatic parenchymal invasion: a mass with a heterogenous pattern or interruption of the pancreatic duct wall by the mass. RESULTS: The diagnostic accuracy rate for differentiating nonneoplastic lesion noninvasive IPMT, and invasive IPMT was 33% by ultrasonography, 38% by computed tomography, 77% by endoscopic ultrasonography, and 67% by intraductal ultrasonography. Sensitivity, specificity and accuracy rates for differentiating neoplastic and nonneoplastic IPMT by ultrasonography was 33%, 100%, 42%, by computed tomography 36%, 100%, 44%, by endoscopic ultrasonography 90%, 71%, 88%, by intraductal ultrasonography 94%, 29%, 84%, respectively. Sensitivity, specificity and accuracy rates for differentiating invasive and noninvasive IPMT by ultrasonography was 25%, 100%, 80%, by computed tomography 33%, 100%, 83%, by endoscopic ultrasonography 55%, 97%, 88%, by intraductal ultrasonography 56%, 91%, 84%, respectively. Diagnostic accuracy for invasive IPMT except minimally invasive cases by endoscopic ultrasonography and intraductal ultrasonography was 80%, based on the results of the examination which demonstrated a higher grade lesion. CONCLUSIONS: With these criteria, ultrasonography and computed tomography showed high specificity, but low sensitivity for the differential diagnosis of neoplastic/nonneoplastic and invasive/noninvasive IPMT. However, endoscopic ultrasonography and intraductal ultrasonography had high sensitivity and diagnostic accuracy for the differential diagnosis of neoplastic/nonneoplastic lesions. Combination of endoscopic ultrasonography and intraductal ultrasonography showed a high accuracy rate in the diagnosis of invasive IPMT. Thus endoscopic ultrasonography and intraductal ultrasonography contributed significantly to the choice of the treatment for IPMT.     

Chronic hypersensitivity pneumonitis caused by Aspergillus complicated with pulmonary aspergilloma

A 57-year-old man consulted our hospital with a history of the gradual onset of dyspnea and a productive cough. Chest computed tomographic (CT) scans showed a nodular shadow in a cavity lesion, and reticulonodular, cystic, and ground-grass opacities in the bilateral lung fields with honeycombing. He was diagnosed as having pulmonary aspergilloma and idiopathic pulmonary fibrosis (IPF). As an outpatient, he suffered from dyspnea upon physical exertion with exacerbation of the high-resolution CT (HRCT) opacities. An inhalation provocation test for Aspergillosis fumigatus was positive and chronic hypersensitivity pneumonitis (CHP) caused by Aspergillus was finally diagnosed. Insidious CHP is sometimes misdiagnosed as IPF. The diagnosis of insidious CHP should be made on the basis of a detailed history, specific HRCT findings, and lymphocyte-dominant bronchoalveolar lavage fluid cell findings.     

Dietary whey protein hydrolysate suppresses development of atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice.

BACKGROUND: Oral administration of enzymatic hydrolysate of cow's milk whey protein (WPH) has been reported to produce an anti-inflammatory effect. Since inflammation plays a role in dermatitis of allergic disease, we examined the influence of WPH on the development of atopic dermatitis (AD)-like skin lesions, induced in NC/Nga mice by the mite antigen Dermatophagoides pteronyssinus (Dp). METHODS: AD-like skin lesions were induced on the pinnae and backs of NC/Nga mice by daily application of Dp for 4 weeks. Mice were fed cow's milk casein (control), WPH or casein protein hydrolysate (CPH) diets for 2 weeks prior to Dp application. Clinical skin conditions were evaluated periodically by a clinical severity score, total serum IgE and soluble E-selectin levels were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: WPH-fed mice showed significantly less AD-like skin lesions than those fed casein diets at 2 and 4 weeks after Dp application. In contrast, CPH-fed mice had manifestations in a similar manner as casein-fed mice did, and did not show an inhibitory effect. Serum soluble E-selectin levels, known as a marker of disease activity in AD patients, were significantly lower in the WPH diet group. CONCLUSIONS: Our results suggest that in addition to its hypoallergenicity an anti-inflammatory function, dietary WPH might be useful for reducing the severity of AD-like skin lesions.     

Rationale and design of a randomized trial to assess the effects of beta-blocker in diastolic heart failure; Japanese Diastolic Heart Failure Study (J-DHF)

BACKGROUND: Heart failure consists of two phenotypes: systolic heart failure and diastolic heart failure (DHF). A growing body of evidence demonstrated benefits of beta-blocker, angiotensin-converting enzyme inhibitor, and angiotensin II receptor blocker in systolic heart failure; however, evidence leading to therapeutic strategy of DHF is lacking. METHODS AND RESULTS: The Japanese Diastolic Heart Failure Study (J-DHF) is a multicenter, prospective, randomized trial designed to assess effects of beta-blocker in patients with DHF. A total of 800 patients (400 patients in each group) will be enrolled. The primary outcome is a composite of cardiovascular death and unplanned admission to hospital for congestive heart failure. Other outcomes include all-cause mortality, worsening of the symptoms of heart failure, or a need for modification of the treatment for heart failure. Serial assessment of echocardiographic and neurohumoral parameters and cost analysis of the treatment regimen will be conducted. The follow-up period is a minimum of 2 years. CONCLUSION: This study will provide important evidences for the treatment of DHF.     

Retinyl palmitate reduces hepatic fibrosis in rats induced by dimethylnitrosamine or pig serum

Background/Aims: Lipid peroxidation has been found to be associated with Ito cell activation. Ito cells are the principal collagen-producing cells and the main storage sites of retinoids. However, the relationship between retinoids and hepatic fibrosis is complex. The aim of this study was to elucidate the role of retinoids as a fibrosuppressant: the effects of retinoids on hepatic fibrosis induced in rats by dimethylnitrosamine or pig serum, as well as on rat Ito cells in primary culture, were examined in order to assess the antioxidant activity of retinoids.Methods: Male Wistar rats were given a single injection of 40 mg/kg dimethylnitrosamine or 0.5 ml PS twice weekly for 10 weeks. In each model, rats were treated with retinyl palmitate for 2 weeks before hepatotoxin treatments or for the last 2 weeks of the treatments. The cumulative amount of retinyl palmitate administered in each experiment was 2, 10, or 20×10⁴ IU/rat.Results: Retinyl palmitate treatment before or after administration of dimethylnitrosamine or pig serum suppressed the induction of hepatic fibrosis, restored hepatic retinyl palmitate levels, prevented increases in hepatic levels of collagen and malondialdehyde, a product of lipid peroxidation, and prevented increases in deposition of type III collagen and the number of α-smooth muscle actin (α-SMA) positive-Ito cells in the liver. Retinyl palmitate supplementation resulted in a dose-dependent reduction of α-SMA expression and an oxidative burst in cultured Ito cells. In addition, retinyl palmitate inhibited Fe²⁺/adenosine 5′-diphosphate-induced lipid peroxidation in rat liver mitochondria and showed radical scavenging activity.Conclusions: These findings suggest that retinyl palmitate may suppress the induction of hepatic fibrosis, at least in part, by the inhibition of Ito cell activation through its antioxidant activity.     

Preload-adjusted 2 wave-intensity peaks reflect simultaneous assessment of left ventricular contractility and relaxation.

BACKGROUND: The magnitudes of the first (WI1) and the second wave-intensity peak (WI2) during the ejection period can be used as indices of left ventricular (LV) contractility and relaxation, respectively. However, use of WI to characterize LV dp/dt and the end-diastolic volume (V ed) relationship may be more problematic, as WI may be affected by changes in preload. METHODS AND RESULTS: The LV pressure-volume data sets, consisting of 23 recordings obtained by the conductance method from 12 heart disease patients, were studied. End-systolic elastance (E es) and volume-axis-intercept (V0) were calculated with varying preload. Time constant of LV relaxation (tau), V ed, and WI were calculated from steady-state averaged data. The E es showed a weak correlation with WI1 (r = 0.46, p < 0.05) but a better correlation with preload-adjusted WI1 [WI1/V ed; r=0.86, WI1/V(ed)2; r = 0.92, WI1/(V ed - V0)2; r = 0.89, all p < 0.01]. Similarly, tau did not correlate with WI2 but did correlate with preload-adjusted WI2 [WI2/V ed; r = -0.73, WI2/V(ed) 2; r = -0.63, WI2/(V ed - V0)2; r = -0.78, all p < 0.01]. CONCLUSIONS: These data demonstrate the importance of preload-adjustment when using the WI index for simultaneous assessment of LV contractility and relaxation.     

Systemic lupus erythematosus associated with recurrent lupus enteritis and peritonitis

We describe the case of a 41-year-old woman with systemic lupus erythematosus (SLE) who suffered from repeated reversible lupus enteritis characterized by marked edematous thickening of the small intestine. Ultrasonography (US) and computed tomography (CT) manifested as an accordion-like appearance and a target-like appearance, respectively. Resolution of gastrointestinal tract wall thickening was observed on follow-up US performed a week after the increase in predinosolone (PSL). We conclude that careful evaluation of sonographic and radiographic findings helps to establish the diagnosis of lupus enteritis.Abbreviations CT Computed tomography - FANA Fluorescent antinuclear antibody - GI Gastrointestinal - SLE Systemic lupus erythematosus - US Ultrasound     

Direct demonstration of the productive capability of cytokines at the single cell level in lung sarcoidosis using multicolor cytometry

BACKGROUND: Sarcoidosis is a chronic systemic disorder of unknown etiology characterized by noncaseating epithelioid cell granulomatous lesions, around which an increasing number of CD4+ T cells infiltrate. These CD4+ T cells may release interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). These cytokines are considered to play an important role in pathogenesis of sarcoidosis. METHODS: We employed a modification of Jung's method using multicolor flow cytometry to assess the capability of single cells obtained from bronchoalveolar lavage (BAL) fluid to produce various cytokines. BAL CD4+ T cell production of IFN-gamma, IL-2 and IL-4 after phorbol ester and ionomycin stimulation were studied. RESULTS: The percentage of IFN-gamma- and IL-2-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers [84.7 +/- 7.5 vs. 51.2 +/- 14.8% (p < 0.005), and 75.3 +/- 8.7 vs. 39.8 +/-11.0% (p < 0.001), respectively]. No significant difference in the percentage of IL-4-producing CD4+ T cells was noted (1.2 +/- 0.6 vs. 3.5 +/- 2.6%; not significant), whereas the absolute number of IL-4-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers (563.6 +/- 330.2 vs. 50.9 +/- 66.9/ml; p < 0.005). In the IL-4-producing CD4+ T cells, about 80% of cells concomitantly produced IFN-gamma and more than 60% of cells also produced IL-2. CONCLUSION: We demonstrate that Th1-like-producing cells are predominant in the CD4+ as well as in the CD8+ T cell subset of patients with sarcoidosis. We for the first time demonstrated concomitant capabilities of BAL CD4+ T cells to produce Th1 and Th2 cytokines at the single cell level by multicolor flow cytometry.     

Abnormal factor VIII Hiroshima: defect in crucial proteolytic cleavage by thrombin at Arg1689 detected by a novel ELISA

We have established an ELISA for detecting thrombin cleavage of the FVIII light chain at Arg¹⁶⁸⁹. The method used a coating alloantibody which recognized amino acid residues 2248–2312 in the C2 domain, together with a second monoclonal antibody, NMC-VIII/10, which recognized residues 1675–1684 in the amino-terminal region of the light chain. FVIII antigen (FVIII:Ag) was measured after treatment of plasma with various concentrations of thrombin. The FVIII:Ag of normal plasma was reduced in a dose-dependent manner by the thrombin, falling to 28% in the presence of 100 U/ml enzyme. The concentration of thrombin that achieved 50% reduction (IC₅₀) was approximately 1·0 U/ml. The plasma of four haemophilia A positive (A⁺) and two haemophilia A reduced (A^R) patients were analysed. The IC₅₀ of all patients was more than 1·0 U/ml, indicating that thrombin cleavage of the FVIII light chain was defective. One haemophilia A⁺ plasma did not respond to thrombin in this ELISA system. The patient (TI) was a haemophiliac with FVIII coagulant activity of 0·04 U/ml and FVIII:Ag of 1·78 U/ml. In addition, immunoblotting of the purified FVIII from TI showed that thrombin cleavage of the 80 kilodalton (kD) light chain was impaired. The patient's DNA was amplified using the polymerase chain reaction with a set of synthetic oligonucleotide primers spanning amino acid residues 1646–1714. Sequence analysis of the amplified DNA fragments revealed a cytosine to thymine transition, converting an arginine 1689 to cysteine. This abnormal FVIII was designated as FVIII Hiroshima. Our ELISA system is a simple and useful method of evaluating the proteolytic cleavage by thrombin at Arg¹⁶⁸⁹.