Guideline No. 451: Asymptomatic Endometrial Thickening in Postmenopausal Women.

OBJECTIVE: To formulate strategies for clinical assessments for endometrial thickening on ultrasound in a postmenopausal woman without bleeding. TARGET POPULATION: Postmenopausal women of any age. OUTCOMES: To reduce unnecessary invasive interventions and investigations in women with asymptomatic endometrial thickening while selectively investigating women at risk for endometrial cancer. BENEFITS, HARMS, AND COSTS: It is anticipated that the adoption of these recommendations would save postmenopausal women unnecessary anxiety, pain, and risk of procedural complications. It is also expected to decrease the cost to the health care system by eliminating unnecessary interventions. EVIDENCE: English language articles from Medline, Cochrane, and PubMed databases for relevant peer-reviewed articles dating from 1995 to 2022 (e.g., asymptomatic endometrial thickness, endometrial cancer, postmenopausal bleeding, transvaginal ultrasound, endometrial biopsy, cervical stenosis, hormone therapies and the endometrium, tamoxifen, tibolone, aromatase inhibitors). Results were restricted to systematic reviews and meta-analyses, randomized controlled trials/controlled clinical trials, and observational studies. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Physicians, including gynaecologists, obstetricians, family physicians, radiologists, pathologists, and internists; nurse practitioners and nurses; medical trainees, including medical students, residents, and fellows; and other providers of health care of the postmenopausal population. SOCIAL MEDIA ABSTRACT: Postmenopausal women often have a thickening of the lining of the uterus found during ultrasound. Without bleeding, an endometrium <11 mm is rarely a serious problem but should be evaluated by a health care provider. SUMMARY STATEMENTS: RECOMMENDATIONS.

Decreased PCSK9 expression in human hepatocellular carcinoma.

BACKGROUND: The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration. Thus, we investigated whether PCSK9 expression is altered in HCC, influencing its ability to harness cholesterol metabolism. METHODS: Thirty-nine patients undergoing partial hepatectomy or liver transplantation for HCC were consented for use of HCC tissue to construct a tissue microarray (TMA). The TMA was immunostained for PCSK9. Imagescope software was used to objectively determine staining, and assess for pathological and clinical correlations. PCSK9 and LDL receptor mRNA levels in flash-frozen HCC and adjacent liver tissue were determined by quantitative RT-PCR. Serum PCSK9 levels were determined by ELISA. RESULTS: By immunohistochemistry, there was significantly lower expression of PCSK9 in HCC as compared to adjacent cirrhosis (p-value < 0.0001, wilcoxon signed-rank test). Significantly greater staining of PCSK9 was present in cirrhosis compared to HCC (p value <0.0001), and positivity (percentage of positive cells) was significantly greater in cirrhosis compared to HCC (p-value < 0.0001). Conversely, significantly higher expression of LDL-R was present in HCC as compared to the adjacent cirrhosis (p-value < 0.0001). There was no significant correlation of PCSK9 staining with grade of tumor, but there were significant correlations between PCSK9 staining and stage of fibrosis, according to spearman correlation test. PCSK9 mRNA levels were relatively less abundant within HCC compared to adjacent liver tissue (p-value =0.08) and normal control tissue (p-value =0.02). In contrast, serum PCSK9 levels were significantly increased among patients with HCC compared to those with chronic liver disease without HCC (p-value =0.029). LDL receptor mRNA was consistantly greater in HCC when compared to normal control tissue (p-value = 0.06) and, in general, was significantly greater in HCC when compared to adjacent liver (p-value = 0.04). CONCLUSIONS: The decreased expression of PCSK9 and conversely increased LDL-R expression in HCC suggests that HCC modulates its local microenvironment to enable a constant energy supply. Larger-scale studies should be conducted to determine whether PCSK9 could be a therapeutic target for HCC.

Impact of a 12-minute educational video prior to initial consultation in a Mature Women's Health and Menopause Clinic.

OBJECTIVES: Assess acceptability of a 12-minute educational video before menopause clinic consultation and evaluate its impact on knowledge and treatment certainty. METHODS: This was a pre-post intervention study among new patients with vasomotor symptoms (VMS) referred to a menopause clinic in Toronto, Canada. Participants completed electronic questionnaires before and after viewing a 12-minute online video covering menopause facts and VMS treatments. Participants' demographic information and referring provider type were recorded. A 19-item true/false knowledge quiz and validated Decision Conflict Scale (DCS) were administered before and after viewing the video along with a validated Acceptability questionnaire after the video. Demographic information and acceptability were summarized descriptively and independent samples t tests compared knowledge and DCS total and subscores before and after viewing the education module. Multivariable analysis was used to identify factors associated with achieving treatment certainty. RESULTS: Seventy-one participants completed pre- and postintervention questionnaires. Mean age was 51.4 ± 6.0 years and most were White (58/71, 81.7%), had a university degree (24/71, 63.3%) and household income >$90,000 (53/71, 74.6%). After the video, there was significant increase in knowledge score (12.7 ± 2.1 vs. 16.9 ± 1.8, P < 0.001) and decrease in all DCS scores (total and five subscores) compared with preintervention scores (P < 0.001). Acceptability was high with 62/71 (87.3%) respondents indicating the tool was useful. Findings were independent of level of education, household income, and referring physician type. CONCLUSION: In a study of predominantly university-educated White women, a 12-minute education module on menopause and VMS treatment was acceptable, there was improved knowledge and decision certainty about VMS treatment.

General anaesthesia versus thoracic paravertebral block for breast surgery: a meta-analysis.

BACKGROUND: Thoracic paravertebral block (TPVB) offers an attractive alternative to general anaesthesia (GA) for ambulatory breast surgery. The aim of this meta-analysis was first to evaluate the safety and efficacy of TPVB for breast surgery, and second to compare TPVB with GA with regard to postoperative pain, nausea and vomiting, opioid consumption and length of hospital stay. METHODS: An electronic and manual search of English- and French-language articles on TPVB in breast surgery (published from January 1980 to June 2010) yielded 41 citations. Two levels of screening identified 11 relevant studies. The Mantel-Haenszel method (fixed effect) was used to perform the meta-analysis. RESULTS: Eleven studies were retained for analysis. When TPVB was used instead of GA, pain scores were significantly decreased at 1 and 6 h postoperatively (mean difference of 2.48 (95%confidence interval (CI): 2.20-2.75) and 1.71 (95%CI: 1.64-1.78), respectively). Furthermore, postoperative analgesic consumption was significantly lower in patients who received TPVB compared with GA (relative risk (RR) 0.23, (95%CI: 0.15-0.37)). TPVB was also associated with significantly less postoperative nausea and vomiting (RR 0.27 (95%CI: 0.12-0.61)). Increased patient satisfaction and a shorter hospital stay also favoured TPVB over GA. CONCLUSIONS: TPVB provides effective anaesthesia for ambulatory breast surgery and can result in significant benefits over GA. However, further studies are required to determine whether these advantages would still be present if an optimal technique for outpatient GA is employed. Adjunctive ultrasonography may contribute to improve the safety of TPVB in breast surgery and requires further investigation.