Prospective external validation of IOTA methods for classifying adnexal masses and retrospective assessment of two-step strategy using benign descriptors and ADNEX: a Portuguese multicenter study.

OBJECTIVE: This study aimed to externally and prospectively validate the International Ovarian Tumor Analysis (IOTA) Simple Rules (SRs), Logistic Regression model 2 (LR2) and Assessment of Different NEoplasias in the adneXa (ADNEX) in a Portuguese population, comparing them with operator subjective assessment (SA), Risk-of-Malignancy Index (RMI), as well as with each other. This study also aimed to retrospectively validate IOTA two-step strategy, using modified benign descriptors (MBDs) followed by the application of ADNEX in cases where MBDs were not applicable (MBDs + ADNEX). METHODS: In this multicenter diagnostic accuracy study, conducted between January 2016 and December 2021, three tertiary referral centers prospectively included consecutive patients with ultrasound diagnosis of at least one adnexal tumor who underwent surgery. All ultrasound assessments were performed by level II or III sonologists with IOTA certification. Patient clinical data and serum cancer antigen (CA125) levels were collected from the hospital databases. Each adnexal mass was classified as benign or malignant using SA, RMI, IOTA SRs, LR2 and ADNEX (with and without CA125). The reference standard was histopathological diagnosis. In the second phase, all adnexal tumors were retrospectively classified using the two-step strategy (MBDs + ADNEX). The sensitivity, specificity, positive (PPV) and negative predictive value (NPV), positive (LR+) and negative likelihood ratio (LR-) as well as overall accuracy were determined for SA, RMI, IOTA SRs, LR2, ADNEX and two-step strategy (MBDs + ADNEX). Receiver-operator characteristic curves were constructed and corresponding areas under the curve (AUC) determined for RMI, LR2 and ADNEX and two-step strategy (MBDs + ADNEX). The ADNEX calibration plots were constructed and estimated by LOESS smoother. RESULTS: Of the 571 included patients, 428 had benign disease, 42 borderline ovarian tumors, 93 primary invasive adnexal cancers and 8 metastatic tumors in adnexa (malignancy prevalence: 25.0%). The operator SA had an overall sensitivity of 97.9% and a specificity of 83.6% for distinguishing between benign and malignant lesions. RMI showed high specificity (95.6%) but very low sensitivity (58.7%), with an AUC of 0.913. The IOTA SRs were applicable in 80.0% of patients, with a sensitivity of 94.8% and a specificity of 98.6%. LR2 revealed a sensitivity of 84.6%, a specificity of 86.9% and an AUC of 0.939, at the malignancy risk cut-off of 10%. At the same cut-off, ADNEX with and without CA125 had a sensitivity of 95.8% and 98.6%, respectively, and a specificity of 82.5% and 79.7%, respectively. The AUC of ADNEX with vs. without CA125 was 0.962 vs. 0.960. The ADNEX model provided heterogeneous results in distinguishing between benign and different subtypes of malignancy, with the highest AUC (0.991) for discriminating benign masses from primary adnexal cancer stage II-IV, and the lowest AUC (0.696) for distinguishing primary adnexal cancer stage I and metastatic lesion in adnexa. The ADNEX calibration plots suggested an underestimation of the predicted risk in relation with the observed proportion of malignancies. The MBDs were applicable in 26.3% of cases (150/571 tumors, none of which were malignant). Similar to the ADNEX model applied in all patients, the two-step strategy using ADNEX in the second step only, with and without CA125, had an AUC of 0.964 and 0.961, respectively. CONCLUSIONS: Our results showed a good to excellent performance of the IOTA methods in the studied Portuguese population, outperforming RMI. ADNEX was superior in accuracy, but interpretation of its ability to distinguish malignant subtypes was fundamentally limited not only by sample size but also by large differences in the prevalence of tumor subtypes. The IOTA MBDs have been shown to be reliable in identifying benign disease. The two-step strategy based on the application of MBDs, followed by the ADNEX model if MBDs are not applicable, has proven to be suitable for daily practice circumventing the need to use electronic support in all patients. This article is protected by copyright. All rights reserved.

The routes of hysterectomy: A survey of current practices amongst members of the International Society for Gynaecologic Endoscopy (ISGE).

OBJECTIVE: This study aimed to explore the current opinion on the routes of hysterectomy amongst the members of the International Society for Gynaecologic Endoscopy (ISGE), as well as the perceptions of potential barriers that inhibit gynaecologists from offering a minimally invasive hysterectomies (MIHs) to their patients. STUDY DESIGN: An anonymous, electronic survey was designed, including the questions about the surgeon location and length of gynaecological practice, preferred approach to hysterectomy, approximate number of surgical cases performed during the year preceding the survey (2021), and potential barriers and contraindications to performing MIHs. It was validated by 12 practicing gynaecologists. Subsequently, the survey was sent to all practicing gynaecologists who are the members of the ISGE. RESULTS: We received a response from 159 members of ISGE (29 % response rate), of which 92 % with ≥ 5 years in practice since the completion of their residency training in Gynaecology and Obstetrics. When asked about the preferred route of hysterectomy for themselves or their relatives, 59 % chose total laparoscopic hysterectomy (TLH), 19 % vaginal hysterectomy (VH), 8 % chose laparoscopically-assisted vaginal hysterectomy (LAVH) and 5 % chose total abdominal hysterectomy (TAH). However, TAH was the most performed hysterectomy procedure undertaken by the respondents in the year preceding the survey. When asked about the main obstacles to performing MIHs, more than half of the respondents highlighted insufficient training during residency and insufficient surgical experience. Only 25 % of the responders acknowledged reading the ISGE guidelines on performing vaginal hysterectomy. CONCLUSIONS: Contrary to a full understanding of the benefits of MIHs, lack of training, as well as insufficient surgical experience and unawareness of existing evidence-based guidelines were the main reasons for the high rate of TAH among the ISGE members who participated in the study. All efforts should be directed at teaching VH and TLH techniques during residency, continuous acquisition of practical experience, and use of validated patient selection guidelines for MIH in daily clinical practice.

The impact of obesity on vaginal hysterectomy and laparoscopically-assisted vaginal hysterectomy outcomes: A randomised control trial.

OBJECTIVES: This prospective randomised control trial aimed to compare outcome measures of vaginal hysterectomy (VH) and laparoscopically-assisted vaginal hysterectomy (LAVH) in obese vs. non-obese women undergoing hysterectomy for benign uterine conditions with a non-prolapsed uterus. The primary objective of the study was to estimate operation time, uterine weight and blood loss amongst obese and non-obese patients undergoing VH and LAVH. The secondary objective was to determine any difference in hospital stay, the need for post-operative analgesia, intra- and immediate post-operative complications, and the rate of conversion to laparotomy for obese vs. non-obese patients undergoing VH and LAVH. STUDY DESIGN: A prospective randomised control study was undertaken in the Department of Obstetrics and Gynaecology of the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Women admitted between January 2017 and December 2019 for hysterectomy due to benign conditions, meeting the inclusion criteria set by the unit (vaginally accessible uterus, uterine size ≤ 12 weeks of gestation or ≤ 280gr on ultrasound examination, pathology confined to the uterus) were included in the study. The VH procedures were performed by the residents in training, under the supervision of specialists with large experience in vaginal surgery. All the LAVHs were performed by one surgeon (AC). In addition to the patient characteristics and surgical approach to hysterectomy, operative time, estimated blood loss, uterine weight, length of hospital stay, intra-operative and immediate post-operative complications were also recorded in obese and non-obese patient groups and comparatively analysed. RESULTS: A total of 227 women were included in the study. 151 patients underwent VH and 76 LAVH, upon randomisation on a 2:1 basis, reflecting the habitual proportion of hysterectomy cases in the Urogynaecology and Endoscopy Unit at CMJAH. No significant differences were found in mean shift of pre-operative to post-operative serum haemoglobin, uterine weight, intra- and immediate post-operative complications, and convalescence period when comparing obese and non-obese patients in both the VH and LAVH groups. There was a statistically significant difference in operating time between the two procedures. The LAVHs took longer compared to the VHs to be performed (62.8 ± 9.3 vs. 29.9 ± 6.6 min in non-obese patients, and 62.7 ± 9.8 vs 30.0 ± 6,9 min for obese patients). All VHs and LAVHs were successfully accomplished without major complications. CONCLUSION: VH and LAVH for the non-prolapsed uterus is a feasible and safe alternative for obese patients demonstrating similar perioperative outcome measures as non-obese women undergoing VH and LAVH. Where possible, VH should be preferred to LAVH as it is a safe route of hysterectomy, with operation time being significantly shorter.

Preferred and actual methods of hysterectomy: a survey of current practices among members of the South African Society of Obstetricians and Gynaecologists

Background. Hysterectomy remains one of the most common operative procedures for benign uterine diseases. Total abdominal hysterectomy (TAH) constitutes the most common approach despite the advantages of minimally invasive hysterectomy (MIH). Objectives. To explore the current opinion on hysterectomy choices amongst members of the South African Society of Obstetricians and Gynaecologists (SASOG), as well as the perceptions and potential barriers that may inhibit gynaecologists from offering MIH to their patients. Methodology. An anonymous survey designed to explore the preferences of practising obstetrician gynaecologists regarding the optimal hysterectomy procedure, and perceived barriers towards MIH. Results. The average age of the respondents (N=152) was 45.7 years, with 88.2% having >5 years' experience in private practice. When asked about the preferred route of hysterectomy for themselves or their relatives, 46.2% chose vaginal hysterectomy (VH), 25.4% chose total laparoscopic hysterectomy (TLH), 15% chose laparoscopic assisted vaginal hysterectomy (LAVH) and 8.5% chose TAH. However, the most commonly performed hysterectomy procedure undertaken by the respondents in the last year was TAH. Only half of the respondents wished to increase their rate of VH and a lesser number to extend their laparoscopic hysterectomy rates. Conclusion. Although the majority of the respondents preferred the minimally-invasive VH or TLH for themselves or their relatives, TAH remains the most common hysterectomy method among SA gynaecologists. This difference could present an ethical dilemma for the gynaecologist. The desire of a minority to change their approach to VH indicates the difficulty in changing attitudes and the need to promote VH as a technique within SASOG

Role of CA125/CEA ratio and ultrasound parameters in identifying metastases to the ovaries in patients with multilocular and multilocular-solid ovarian masses.

OBJECTIVES: To investigate ultrasound features and the best cut-off value of the cancer antigen 125/carcinoembryonic antigen (CA125/CEA) ratio to discriminate ovarian metastases from benign and primary malignant ovarian neoplasms in two selected groups of morphological ovarian masses, namely multilocular masses with five or more locules and multilocular-solid masses. METHODS: Patients with multilocular (five or more locules) or multilocular-solid ovarian masses, operated on within 3 months of ultrasound examination, and with tumor markers (CEA and CA125) available at diagnosis, were identified retrospectively from three ultrasound centers. The masses were described using the International Ovarian Tumor Analysis (IOTA) terminology. Ultrasound and clinical characteristics were compared between those with an ovarian neoplasm (including benign and primary malignant neoplasms) and those with an ovarian metastasis. Receiver-operating characteristics curve (ROC) analysis was used to evaluate the ability of CA125, CEA and CA125/CEA to differentiate between ovarian neoplasms and ovarian metastases, and their predictive performance was assessed. RESULTS: In total, 350 (88.4%) patients with an ovarian neoplasm (including 99 benign, 43 borderline and 197 primary epithelial ovarian carcinomas, seven malignant rare tumors and four other types of invasive ovarian tumor) and 46 (11.6%) patients with an ovarian metastasis were analyzed. On ultrasound examination, ovarian neoplasms were smaller than ovarian metastases (median largest diameter, 97 (range, 20-387) mm vs 146 (range, 43-259) mm, respectively; P < 0.0001) and presented with a lower number of cysts with > 10 locules (18.9% vs 54.3%; P < 0.0001). ROC curve analysis showed that the best cut-off value of CEA for distinguishing between ovarian neoplasms and ovarian metastases was 2.33 ng/mL. The predictive performance of this CEA cut-off value was: area under the curve (AUC), 0.791 (95% CI, 0.711-0.870); accuracy, 73.7%; sensitivity, 73.1%; specificity, 78.3%; positive predictive value (PPV), 96.2%; and negative predictive value (NPV), 27.7%. The best cut-off value of CA125/CEA for distinguishing between ovarian neoplasms and ovarian metastases was 11.92. The predictive performance of this CA125/CEA cut-off value was: AUC, 0.758 (95% CI, 0.683-0.833); accuracy, 79.8%; sensitivity, 82.3%; specificity, 60.9%; PPV, 94.1%; and NPV, 31.1%. CONCLUSIONS: CA125/CEA ratio and CEA alone did not show any significant difference in their ability to distinguish between ovarian neoplasms (including benign and malignant) and ovarian metastases in masses with multilocular and those with multilocular-solid morphology. Therefore, in this morphological subgroup of ovarian masses, CEA alone is sufficient to differentiate between ovarian neoplasms and ovarian metastases. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Simple and sensitive antimalarial drug screening in vitro and in vivo using transgenic luciferase expressing Plasmodium berghei parasites.

We report two improved assays for in vitro and in vivo screening of chemicals with potential anti-malarial activity against the blood stages of the rodent malaria parasite Plasmodiumberghei. These assays are based on the determination of luciferase activity (luminescence) in small blood samples containing transgenic blood stage parasites that express luciferase under the control of a promoter that is either schizont-specific (ama-1) or constitutive (eef1alphaa). Assay 1, the in vitro drug luminescence (ITDL) assay, measured the success of schizont maturation in the presence of candidate drugs quantifying luciferase activity in mature schizonts only (ama-1 promoter). The ITDL assay generated drug-inhibition curves and EC(50) values comparable to those obtained with standard in vitro drug-susceptibility assays. The second assay, the in vivo drug-luminescence (IVDL) assay, measured parasite growth in vivo in a standard 4-day suppressive drug test, monitored by measuring the constitutive luciferase activity of circulating parasites (eef1alphaa promoter). The IVDL assay generates growth-curves that are identical to those obtained by manual counting of parasites in Giemsa-stained smears. The reading of luminescence assays is rapid, requires a minimal number of handling steps and no experience with parasite morphology or handling fluorescence-activated cell sorters, produces no radioactive waste and test-plates can be stored for prolonged periods before processing. Both tests are suitable for use in larger-scale in vitro and in vivo screening of drugs. The standard methodology of anti-malarial drug screening and validation, which includes testing in rodent models of malaria, can be improved by the incorporation of such assays.

Variability of essential oils of Satureja montana L. and Satureja kitaibelii wierzb. ex Heuff. from the central part of the balkan peninsula.

The results of the essential oil composition confirm that there are differences between populations within the same subspecies (Satureja montana ssp. montana, between the subspecies (Satureja montana ssp. montana and Satureja montana ssp. pisidica) and the species (Satureja montana and S. kitabelii). The essential oil composition of S. montana ssp. montana is more related to the Satureja montana ssp. pisidica than S. kitaibelii which separates as a whole species.