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     

Overexpression of cyclin‐dependent kinase 4 protein in extramammary Paget's disease

Cyclin‐dependent kinase 4 and 6 (CDK4/6) plays an important role in cell cycle progression, and the CDK4/6–cyclin D1 complex controls the cell cycle transition from G₁ phase to S phase. CDK4 is enhanced in several types of cancers and CDK4/6 inhibitors attenuate the proliferation of several types of cancer in vitro/in vivo. The purpose of our study was to investigate the expression pattern of CDK4 and evaluate its clinical importance in extramammary Paget's disease (EMPD). Almost all EMPD tissues were positive for CDK4, and metastatic lesions had a similar immunostaining intensity to primary lesions. In addition, CDK4 protein levels were positively correlated with those of cyclin D1 protein. Taken together, CDK4 may assume a crucial role in EMPD progression.