Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: Analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125.

OBJECTIVES: To assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. METHODS: This retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. RESULTS: We observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level- but not HE4 - during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 - but not CA-125 - before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27-5.79). CONCLUSION: Monitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models.

Effects of letrozole alone or in combination with gonadotropins on ovulation induction and clinical pregnancy in women with polycystic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare letrozole in combination with gonadotropins versus letrozole monotherapy in ovulation induction and clinical pregnancy among infertile women with polycystic ovarian syndrome (PCOS). METHODS: Several databases were searched for available clinical trials from inception until March 2023. We selected randomized controlled trials (RCTs) that compared sequential letrozole/gonadotropin versus letrozole alone among infertile women who met the Rotterdam criteria for PCOS. RevMan software was used to perform our meta-analysis. Our primary outcomes were ovulation and clinical pregnancy rates. Our secondary outcomes were endometrial thickness, number of mature follicles (diameter ≥ 18 mm), and incidence of miscarriage and ovarian hyperstimulation syndrome (OHSS). RESULTS: Six RCTs were retrieved with a total number of 723 patients. The ovulation and clinical pregnancy rates were significantly higher among the letrozole/gonadotropin group versus the letrozole monotherapy group (p < 0.001). In addition, there were significant improvements in endometrial thickness and number of mature follicles in the letrozole/gonadotropin group. There were no significant differences between the two groups regarding incidence of miscarriage and ovarian hyperstimulation syndrome. CONCLUSION: Letrozole in combination with gonadotropin is superior to letrozole alone in improving ovulation induction and clinical pregnancy among PCOS patients. More trials are required to confirm our findings.

Intraperitoneal lidocaine instillation during abdominal hysterectomy: A systematic review and meta-analysis of randomized placebo-controlled trials.

AIM: To perform a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) that inspected the analgesic benefits of intraperitoneal lidocaine instillation among patients undergoing abdominal hysterectomy. METHODS: Five electronic databases were inspected from till August 5, 2021. The eligible RCTs were evaluated for risk of bias. The pooled endpoints were summarized as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI). RESULTS: Five RCTs met the inclusion criteria comprising 263 patients (119 and 117 patients were allocated to lidocaine and control group, respectively). The included RCTs demonstrated a low risk of bias. The postoperative pain score at rest was significantly lower in favor of the lidocaine group (MD=-1.01, 95% CI [-1.20, -0.81], p<0.001), and subgroup analysis demonstrated the same at 2, 4, 8, 12, 24, and 48 h postoperatively. Moreover, the postoperative pain score at moving was significantly lower in favor of the lidocaine group (MD=-0.67, 95% CI [-1.01, -0.33], p<0.001), and subgroup analysis demonstrated the same at 2 and 48 h postoperatively. The postoperative morphine consumption during 0-24 h was significantly lower in favor of the lidocaine group (n = 5 RCTs, MD=-7.29 mg, 95% CI [-13.22, -1.37], p = 0.02). The rate of postoperative vomiting was significantly lower in favor of the lidocaine group (n = 4 RCTs, RR=0.54, 95% CI [0.31, 0.95], p = 0.03). CONCLUSION: Among patients undergoing abdominal hysterectomy, intraperitoneal lidocaine instillation is feasible, cheap, safe, and associates with effective analgesia in terms of reduced postoperative pain score and morphine consumption.