Localization of mRNA for SHIP2, SH2 domain-containing inositol polyphosphate 5-phosphatase, in the brain of developing and mature rats

The localization of mRNA for SHIP2, SH2 domain containing inositol 5-phosphatase SHIP isozyme, was examined by in situ hybridization histochemistry in the brain of developing and mature rats. SHIP2 mRNA was first detected in the ventricular germinal zone at embryonic stages. As the postnatal development proceeded, the expression signal was evident in cell of the white matters, presumptive oligodendrocytes, and no significant expression was seen in neurons throughout the development.     

Periodic Protrusion of Right Coronary Cusp into Left Ventricular Outflow Tract Due to Detachment from the Aortic Annulus Complicated with Infective Endocarditis

We describe the imaging of unusual dislocation of right coronary cusp into left ventricular outflow tract (LVOT) due to the infective endocarditis. Although the two‐dimensional echocardiography identified a protruding mass in LVOT, the three‐dimensional echocardiography precisely demonstrated the spatial anatomy of the aortic root, which was confirmed by the surgical operation, implicating the usefulness of three‐dimensional echocardiography in this rare anomaly.     

Contrast‐enhanced harmonic endoscopic ultrasonography for differential diagnosis of localized gallbladder lesions

Background and Aim

Differential diagnosis of localized gallbladder lesions is challenging. The aim of the present study was to evaluate the utility of contrast‐enhanced harmonic endoscopic ultrasonography (CH‐EUS) for diagnosis of localized gallbladder lesions.

Methods

One hundred and twenty‐five patients with localized gallbladder lesions were evaluated by CH‐EUS between March 2007 and February 2014. This was a single‐center retrospective study. Utilities of fundamental B‐mode EUS (FB‐EUS) and CH‐EUS in the differentiation of gallbladder lesions and sludge plug were initially compared. Thereafter, these two examinations were compared with respect to their accuracy in the diagnosis of malignant lesions. Five reviewers blinded to the clinicopathological results evaluated microcirculation patterns in the vascular and perfusion images.

Results

In the differentiation between gallbladder lesions and sludge plug, FB‐EUS had a sensitivity, specificity, and accuracy of 82%, 100%, and 95%, respectively, whereas CH‐EUS had a sensitivity, specificity, and accuracy of 100%, 99%, and 99%, respectively. FB‐EUS‐based diagnosis of carcinomas based on tumor size and/or shape had a sensitivity, specificity, and accuracy of 61–87%, 71–88%, and 74–86%, respectively. Additional information regarding irregular vessel patterns in the vascular image and/or heterogeneous enhancement in the perfusion image on CH‐EUS increased the sensitivity, specificity, and accuracy for the diagnosis of carcinomas to 90%, 98%, and 96%, respectively. There was a significant difference between FB‐EUS and CH‐EUS in terms of carcinoma diagnosis.

Conclusion

CH‐EUS was useful for the evaluation of localized gallbladder lesions.     

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH ({"type":"clinical-trial","attrs":{"text":"NCT01140347","term_id":"NCT01140347"}}NCT01140347) and REACH-2 ({"type":"clinical-trial","attrs":{"text":"NCT02435433","term_id":"NCT02435433"}}NCT02435433).Subject terms: Oncology, Biomarkers