Evaluating resectoscopy and the levonorgestrel intrauterine system for intermenstrual bleeding associated with cesarean scar defects: A retrospective study of treatment outcomes.

AIM: To compare and evaluate the efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUD) and resectoscopy remodeling procedure for intermenstrual bleeding associated with previous cesarean delivery scar defect (PCDS). METHODS: A retrospective comparative study was conducted on patients with PCDS receiving LNG-IUD (levonorgestrel 20 µg/24 h, N = 33) or resectoscopy remodeling (N = 27). Treatment outcomes were compared over 1, 6, and 12 months. Outcomes in patients with a retroverted or large uterus size, defect size, and local vascularization also were evaluated. RESULTS: At 12 months post-treatment, there were no significant differences between groups in efficacy rate; however, the reduction of intermenstrual bleeding days was higher in the LNG-IUD group than in the resectoscopy group (13.6 vs. 8.5 days, p = 0.015). Within the first year, both groups experienced a reduction in bleeding days, but the decrease was greater in the LNG-IUD group. Individuals exhibiting increased local vascularization at the defect site experienced more favorable outcomes in the LNG-IUD group than the resectoscopy group (p = 0.016), and who responded poorly tended to have a significantly larger uterus in the LNG-IUD group (p = 0.019). No significant differences were observed in treatment outcomes for patients with a retroverted uterus or large defect in either group. CONCLUSIONS: Our findings support that the LNG-IUD is as effective as resectoscopy in reducing intermenstrual bleeding days associated with PCDS and can be safely applied to patients without recent fertility aspirations. Patients with increased local vascularization observed during hysteroscopy may benefit more from LNG-IUD intervention than resectoscopy.

Estrogen/Progesterone Receptor Expression and Cancer Antigen 125 Level as Preoperative Predictors to Estimate Lymph Node Metastasis in Endometrioid Endometrial Cancer.

Loss of estrogen receptor/progesterone receptor (ER/PR) in endometrial cancer (EC) is associated with tumor progression and poor outcomes. Elevated pretreatment cancer antigen 125 (CA 125) level is a risk factor for lymph node metastasis (LNM). We evaluated whether the combination of ER/PR expression and CA 125 level could be used as a biomarker to predict LNM. We retrospectively investigated patients with endometrioid EC who underwent complete staging surgery during January 2015 to December 2020. We analyzed ER/PR status using immunohistochemical staining, and quantified its expression using the sum of both ER/PR H-scores. Receiver operating characteristic curves were used to identify optimal cutoff values of H-score and CA 125 levels for predicting LNM. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. In 396 patients, the optimal cutoff values of the ER/PR H-score and CA 125 were 407 (area under the receiver operating characteristic curve: 0.645, P=0.001) and 40 U/mL (area under the receiver operating characteristic curve: 0.762, P<0.001), respectively. Multivariate analysis showed that CA 125 ≥40 UmL (odds ratio: 10.02; 95% CI: 4.74-21.18) and ER/PR H-score <407 (odds ratio: 4.20; 95% CI: 1.55-11.32) were independent predictors. An LNM predictive nomogram was constructed using these 2 variables and our model yielded a negative predictive value and negative likelihood ratio of 98.3% and 0.14, respectively. ER/PR expression with pretreatment CA 125 levels can help estimate LNM risk and aid in decision-making regarding the need for lymphadenectomy in patients with endometrioid EC.

Pretreatment carcinoembryonic antigen combined with cancer antigen-125 for predicting lymph node metastasis in endometrial carcinoma: a retrospective cohort study.

PURPOSE: To investigate whether the cost-effective, pretreatment tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) can be used to predict lymph node metastasis (LNM) in endometrioid-type endometrial cancer (EC) and to develop a predictive model. METHODS: This was a single-center retrospective study of patients with endometrioid-type EC who underwent complete staging surgery between January 2015 and June 2022. We identified the optimal cut-off values of CEA and CA-125 for predicting LNM using receiver operating characteristic (ROC) curves. Stepwise multivariate logistic regression analysis was used to identify independent predictors. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. RESULTS: The optimal cut-off values of CEA and CA-125 were 1.4 ng/mL (area under the ROC curve (AUC) 0.62) and 40 U/mL (AUC 0.75), respectively. Multivariate analysis showed that CEA (odds ratio (OR) 1.94; 95% confidence interval (CI) 1.01-3.74) and CA-125 (OR 8.75; 95% CI 4.42-17.31) were independent predictors of LNM. Our nomogram showed adequate discrimination with a concordance index of 0.78. Calibration curves for the probability of LNM showed optimal agreement between the predicted and actual probabilities. The risk of LNM for markers below the cut-offs was 3.6%. The negative predictive value and negative likelihood ratio were 96.6% and 0.26, respectively, with moderate ability to rule out the possibility of LNM. CONCLUSION: We report a cost-effective method of using pretreatment CEA and CA-125 levels to identify patients with endometrioid-type EC who are at a low risk for LNM, which may guide decision-making regarding aborting lymphadenectomy.

Compatibility of Flavoring Agents in Compounding Extemporaneous Omeprazole Oral Liquid.

In a previous study, the results of which were provided in an article published in the International Journal of Pharmaceutical Compounding, it was determined that FLAVORx's Grape flavor in extemporaneously compounded omeprazole oral liquid was found suitable. A follow-up study was conducted in which the authors explored four additional flavors (Professional Compounding Centers of America's Cherry Concentrate and their Orange Concentrate, and FLAVORx's Bubble Gum flavor and their Watermelon flavor) to allow pharmacists and patients greater flexibility and options to flavor omeprazole oral liquid. Oral liquids were compounded using 20-mg omeprazole delayed-release capsules, 8.4% sodium bicarbonate, and each of four flavors to reach drug concentration at 2 mg/mL and flavor at 1.2% v/v (n=3). After the delayed-release pellets were disintegrated, the prescription bottles were stored in cold temperature overnight. For flavor alone in 8.4% sodium bicarbonate solution, samples were prepared the same as above except no omeprazole delayed-release capsules were added. High-performance liquid chromatographic assay was adopted from the United States Pharmacopeia's Omeprazole Monograph, but it is for the unflavored oral liquid. In order to ensure assay robustness, stability indication tests, 0.1 N HCl (acid), 0.1 N NaOH (base), 50°C (heat), and 3% hydrogen peroxide were also performed to the flavored omeprazole oral liquids, as well as to the individual flavor alone in sodium bicarbonate solution without omeprazole. Professional Compounding Centers of America's Cherry Concentrate, Orange Concentrate, and FLAVORx's Watermelon flavor showed no interference with the drug, and the assays were robust. However, FLAVORx's Bubble Gum flavor displayed five mini peaks at 280 nm with one embedded in omeprazole peak. The resolution of a Bubble Gum peak immediately next to an omeprazole peak computed by column kinetics was 0.91, while the separation factor was 1.15. A good separation is generally >1.5. This study examined only the Cherry Concentrate, Orange Concentrate, Bubble Gum flavor, and Watermelon flavor from the specified manufacturers. An insignificant interference was shown between FLAVORx's Bubble Gum flavor with omeprazole. The results are not intended to infer that all brands of the same flavor names would react the same way. Omeprazole and all four studied flavors should be protected from oxidation insult.

Chemoenzymatic Synthesis of DSGb5 and Sialylated Globo-series Glycans.

Sialic-acid-binding, immunoglobulin-type lectin-7 (Siglec-7) is present on the surface of natural killer cells. Siglec-7 shows preference for disialylated glycans, including α(2,8)-α(2,3)-disialic acids or internally branched α(2,6)-NeuAc, such as disialosylglobopentaose (DSGb5). Herein, DSGb5 was synthesized by a one-pot multiple enzyme method from Gb5 by α2,3-sialylation (with PmST1) followed by α2,6-sialylation (with Psp2,6ST) in 23 % overall yield. DSGb5 was also chemoenzymatically synthesized. The protection of the nonreducing-end galactose of Gb5 as 3,4-O-acetonide, 3,4-O-benzylidene, and 4,6-O-benzylidene derivatives provided DSGb5 in overall yields of 26 %, 12 %, and 19 %, respectively. Gb3, Gb4, and Gb5 were enzymatically sialylated to afford a range of globo-glycans. Surprisingly, DSGb5 shows a low affinity for Siglec-7 in a glycan microarray binding affinity assay. Among the synthesized globo-series glycans, α6α3DSGb4 shows the highest binding affinity for Siglec-7.