Extrahepatic bile duct stricture and elevated CA 19-9: malignant or benign?

Biliary obstruction due to a proximal bile duct stricture is commonly a result of cholangiocarcinoma. We describe a patient who began having intermittent episodes of jaundice 3 years after cholecystectomy. Despite endoscopic placement of a biliary stent and adequate biliary decompression, the serum CA 19-9 level remained elevated at 58 U/ml (normal <37 U/ml). Segmental bile duct resection and Roux-en-Y hepaticojejunostomy were done. The stricture was caused by a traumatic bile duct neuroma. Diagnostic and therapeutic considerations of this entity are discussed, with special emphasis on the value of noninvasive biliary imaging by magnetic resonance imaging (MRI), the utility and interpretation of the CA 19-9 level, and the role for resection or surgical biliary decompression.     

Net Improvement of Correct Answers to Therapy Questions After PubMed Searches: Pre/Post Comparison

Background

Clinicians search PubMed for answers to clinical questions although it is time consuming and not always successful.

Objective

To determine if PubMed used with its Clinical Queries feature to filter results based on study quality would improve search success (more correct answers to clinical questions related to therapy).

Methods

We invited 528 primary care physicians to participate, 143 (27.1%) consented, and 111 (21.0% of the total and 77.6% of those who consented) completed the study. Participants answered 14 yes/no therapy questions and were given 4 of these (2 originally answered correctly and 2 originally answered incorrectly) to search using either the PubMed main screen or PubMed Clinical Queries narrow therapy filter via a purpose-built system with identical search screens. Participants also picked 3 of the first 20 retrieved citations that best addressed each question. They were then asked to re-answer the original 14 questions.

Results

We found no statistically significant differences in the rates of correct or incorrect answers using the PubMed main screen or PubMed Clinical Queries. The rate of correct answers increased from 50.0% to 61.4% (95% CI 55.0%-67.8%) for the PubMed main screen searches and from 50.0% to 59.1% (95% CI 52.6%-65.6%) for Clinical Queries searches. These net absolute increases of 11.4% and 9.1%, respectively, included previously correct answers changing to incorrect at a rate of 9.5% (95% CI 5.6%-13.4%) for PubMed main screen searches and 9.1% (95% CI 5.3%-12.9%) for Clinical Queries searches, combined with increases in the rate of being correct of 20.5% (95% CI 15.2%-25.8%) for PubMed main screen searches and 17.7% (95% CI 12.7%-22.7%) for Clinical Queries searches.

Conclusions

PubMed can assist clinicians answering clinical questions with an approximately 10% absolute rate of improvement in correct answers. This small increase includes more correct answers partially offset by a decrease in previously correct answers.     

A phase II study of Hsp-7 (SGN-00101) in women with high-grade cervical intraepithelial neoplasia

OBJECTIVE: Approximately 2 million women worldwide are infected with high-risk human papillomaviruses (HPV), resulting in a substantial risk for the development of invasive lower genital malignancies. This study was undertaken to determine the effects of vaccination with a protein encoding a bacterial heat shock protein fused to sequences from the oncogenic E7 protein of HPV-16 in women with high-grade cervical intraepithelial neoplasia. Endpoints included lesion regression, immune response, and viral clearance. METHODS: Twenty-one women were prospectively entered into an IRB-approved Phase II study. All women had biopsy-proven high-grade cervical intraepithelial neoplasia and persistent post-biopsy lesions visible by colposcopy. Four injections of HPV-16 Hsp E7 fusion protein at a dose of 500 mug were given 3 weeks apart after which Loop Electrosurgical Excision of the Transformation Zone (LLETZ) was performed. Immune parameters were evaluated pre-vaccine and at the time of LLETZ, and HPV testing was performed at intervals before and after LLETZ. Study subjects were followed for 1 year after LLETZ. RESULTS: Seven of 20 women (35%) evaluable for response had complete regression of their intraepithelial neoplasia at the time of LLETZ, 1 (5%) had regression to CIN I, 11 (55%) had stable disease and 1 (5%) had progression due to enlargement of her lesion. Immune responses were seen in 9 of the 17 women tested; 5 of the 7 complete responders had an immune response. Only 5 of 21 women had HPV-16 or -18. HPV clearance was not associated with lesion regression. CONCLUSION: Hsp-7 (SGN-00101), at this dose and schedule induced lesion regression in women with high-grade intraepithelial neoplasia. The fact that regression was correlated with immune response suggests that enhancing the immunogenicity of this vaccine may lead to improvement in the rate of lesion eradication.