Challenges During Review of COVID-19 Research Proposals: Experience of Faculty of Medicine, Ain Shams University Research Ethics Committee, Egypt.

The COVID-19 pandemic resulted in an overwhelming increase in research studies submitted to research ethics committees (RECs) presenting many ethical challenges. This article aims to report the challenges encountered during review of COVID-19 research and the experience of the Faculty of Medicine, Ain Shams University Research Ethics Committee (FMASU REC). From April 10, 2020, until October 13, 2020, the FMASU REC reviewed 98 COVID-19 research protocols. This article addressed the question of how to face an overwhelming amount of research submitted to the REC while applying the required ethical principles. Ethical challenges included a new accelerated mode of review, online meetings, balance of risks vs. benefits, measures to mitigate risks, co-enrolment in different studies, protection of a vulnerable COVID-19 population, accelerated decisions, online research, how to handle informed consent during the pandemic, and justification of placebo arm.

KLK10 exon 3 unmethylated PCR product concentration: a new potential early diagnostic marker in ovarian cancer? - A pilot study.

BACKGROUND: KLK10 exon 3 hypermethylation correlated to tumor-specific lack of KLK10 expression in cancer cell lines and primary tumors. In the present study we investigate the possible role of KLK10 exon 3 methylation in ovarian tumor diagnosis and prognosis. RESULTS: Qualitative methylation-specific PCR (MSP) results did not show statistically significant differences in patient group samples (normal and tumor) where all samples were positive only for the unmethylated-specific PCR except for two malignant samples that were either doubly positive (serous carcinoma) or doubly negative (Sertoli-Leydig cell tumor) for the two MSP tests. However, KLK10 exon 3 unmethylated PCR product concentration (ng/µl) showed statistically significant differences in benign and malignant patient group samples; mean ± SD (n): tumor: 0.077 ± 0.035 (14) and 0.047 ± 0.021 (15), respectively, p-value = 0.011; and normal: 0.094 ± 0.039 (7) and 0.046 ± 0.027 (6), respectively, p-value = 0.031. Moreover, ROC curve analysis of KLK10 exon 3 unmethylated PCR product concentration in overall patient group samples showed good diagnostic ability (AUC = 0.778; p-value = 0.002). Patient survival (living and died) showed statistically significant difference according to preoperative serum CA125 concentration (U/ml); median (n): 101.25 (10) and 1252 (5), respectively, p-value = 0.037, but not KLK10 exon 3 unmethylated PCR product concentration (ng/µl) in overall malignant patient samples; mean ± SD (n): 0.042 ± 0.015 (14) and 0.055 ± 0.032 (7), p-value = 0.228. CONCLUSION: To the best of our knowledge, this is the first report on KLK10 exon 3 unmethylated PCR product concentration as potential early epigenetic diagnostic marker in primary ovarian tumors. Taken into account the limitations in our study (small sample size and semi-quantitative PCR product analysis) further studies are strongly recommended.

Ovarian function in female survivors of childhood malignancies.

BACKGROUND: Chemotherapy-induced infertility is a common side effect observed in women of fertile age after treatment for malignant disease. OBJECTIVES: to study gonadal function and fertility in female survivors of childhood malignancies. PATIENTS AND METHODS: Study included 30 female cancer survivors and 30 age-matched healthy females as a control group. Data collected regarding; type of malignancy, age at diagnosis, duration on and off treatment, treatment received (radiation or chemotherapeutic regimens), sexual, menstrual, pregnancy, and fertility histories were also recorded. Laboratory investigations included; T4, thyroid stimulating hormone (TSH), leutinizing hormone (LH), follicular stimulating hormone (FSH), and anti-Mullerian hormone (AMH). Pelviabdominal ultrasound was done to estimate the mean ovarian volume. RESULTS: Among patients; 80% had normal menarche and 6 (20%) had delayed menarche (P > .05). There was higher LH and FSH levels and lower AMH levels in patients (P < .05) with no significant difference in thyroid function tests (P > .05). Lower mean ovarian volume was observed among female survivors (6.32 ± 2.31 cm(3)) (P = .041). There was a higher FSH and LH levels among female survivors of solid tumors compared to those with hematological tumors (P = .05 and .04 respectively). There was a significant positive correlation between FSH level and patients' age at start of malignancy (r = 0.65, P = .014), age of menarche (r = 0.74, P = .036), and duration of treatment (r = 0.54, P = .025).There was a significant negative correlation between age of menarche and AMH level (r = -0.61, P = .03). CONCLUSION: Female survivors of childhood malignancies had reduced ovarian reserve and reduced mean ovarian volume, especially those with older age, older age of menarche, and longer treatment duration.

Endometrial/uterine corporeal volume ratio (EV/UCV) as predictor of malignancy in women with postmenopausal bleeding.

OBJECTIVE: To evaluate the role of endometrial/uterine corporeal volume ratio for the prediction of endometrial malignancy in cases of postmenopausal bleeding. METHODS: Endometrial volumes and uterine body volumes excluding cervices measured by VOCAL (virtual organ computer-aided analysis) were estimated in 160 women with postmenopausal bleeding. Endometrial/uterine corporeal volume ratios were calculated for all. Endometrial biopsies and histopathological results were obtained for all. One hundred normal postmenopausal women were included as controls. RESULTS: Histopathological results of the 160 women with postmenopausal bleeding revealed 53 atypia, 27 endometrial cancer and 80 benign conditions. An endometrial/uterine volume (EV/UCV) ratio of a cutoff value >0.017 was predictive of malignancy. Endometrial/uterine volume ratio was more sensitive than endometrial volume and endometrial thickness for prediction of endometrial cancer. CONCLUSION: An endometrial/uterine volume ratio (EV/UCV) >0.017 is predictive of malignancy. (EV/UCV) was more accurate in the prediction of malignancy than endometrial thickness and endometrial volume.

Diagnostic value of serum kallikrein-related peptidases 6 and 10 versus CA125 in ovarian cancer.

OBJECTIVES: To assess the diagnostic value of serum KLK6 and KLK10 in patients with ovarian tumor in comparison to serum CA125. METHODS: Based on clinical and sonographic findings, 90 patients were consecutively recruited at the Gynecological Oncology Unit, Ain Shams University Maternity Hospital. Preoperative serum KLK6 and/or KLK10 were determined by enzyme-linked immunosorbent assay technique. The patients' final diagnoses were those of the histopathological reports. RESULTS: There were 27 malignant versus 63 benign cases. Serum markers' diagnostic specificity and sensitivity were 80.3/72.7, 56.8/64.0, and 39.53/58.3 for CA125, KLK6, and KLK10, respectively. Combination of CA125 with either of the other 2 markers revealed diagnostic enhancement with KLK10 (85.37/73.00) but not with KLK6 (42.86/86.36). CONCLUSIONS: In ovarian cancer, serum KLK6 and KLK10 may have much lower overall sensitivities than serum CA125. However, whereas serum KLK6 may improve the sensitivity of CA125, serum KLK10 may have the highest specificity among the 3 markers.

Direct visual inspection of the cervix with Lugol iodine for the detection of premalignant lesions.

OBJECTIVE: To evaluate the feasibility and efficiency of direct visual inspection after Lugol iodine painting in detecting cervical premalignant and malignant lesions. MATERIALS AND METHODS: This study included 1,012 women recruited from gynecology outpatient clinic screened for premalignant or malignant lesions of the cervix. All women underwent cervical smear test, direct visual inspection of the cervix after painting with acetic acid (DVI-A) and after painting with Lugol iodine (DVI-LI). Abnormal test results were referred for colposcopy and biopsy. RESULTS: Cervical smears were abnormal in 24 women (2.4%). Direct visual inspection of the cervix after painting with acetic acid test was abnormal in 92 women (9.1%). Direct visual inspection after Lugol iodine painting test was abnormal in 93 women (9.2%). There were 106 women (10.5%) referred for colposcopy, with 88 women (8.8%) having biopsies taken. Biopsies showed premalignant and malignant lesions in 44 cases only. There were 35 low-grade squamous intraepithelial lesion, 5 high-grade squamous intraepithelial lesion, and 4 cervical cancers. Test efficiency parameters particularly sensitivity, specificity, and positive and negative predictive values of DVI-LI were 97.7%, 94.8%, 46.2%, and 99.9%, respectively; those of cytology were 22.7%, 97.6%, 41.7%, and 96.6%, respectively, and those of DVI-A were 90.9%, 94.6%, 43.5%, and 99.6%, respectively. CONCLUSIONS: Direct visual inspection after Lugol iodine painting is feasible and easy to perform with superior sensitivity to cervical cytology and DVI-A in detecting cervical premalignant and malignant lesions. Direct visual inspection after Lugol iodine painting can be used as an efficient primary screening tool with a satisfactory low biopsy rate in low resources settings.

Preoperative serum inhibin levels in patients with ovarian tumors.

AIM: To assess the value of preoperative determination of serum inhibin levels in the prediction of malignancy in women with ovarian tumors. The prediction of malignancy not only helps patient counseling regarding prognosis and extent of surgery but also allows for proper specialist referral. METHODS: Fifty women with clinically diagnosed ovarian tumors before surgery (patients group) and 32 healthy non-pregnant women in the early follicular phase of their cycle (controls) were studied. Serum inhibin (total) levels and CA125 were determined using immunoenzymometric assay and enzyme immunoassay, respectively. RESULTS: In the patients group, 31 women had malignant ovarian tumors and 19 had benign tumors. Mean (SEM) serum inhibin levels were 0.94 (0.13) U/mL in the control group, 0.91 (0.7) U/mL in women with benign tumors and 1.9 (0.12) U/mL in women with malignant tumors; the differences are statistically significant (P < 0.01). Inhibin levels were significantly higher in women with late-stage malignant ovarian tumors (III and IV) than in early stages (I and II) and showed no significant difference in relation to menopausal status or the presence of ascites. Taking the 95th centile inhibin level in the control group (1.155 U/mL) as a discriminator level, all women with benign tumors were negative while 67.7% of women with malignant tumors were positive. The inhibin level testing predicted malignancy with a sensitivity of 67.7%, 100% specificity, 100% positive predictive value and 65.52% negative predictive value. Combining CA125 levels (>35 U/mL) with serum inhibin levels (> 1.155 U/mL) improves sensitivity of predicting malignancy to 83.87% and negative predictive value to 75% while maintaining a specificity of 100% and a positive predictive value of 100%. Combining serum inhibin with sonography achieves 96.77% sensitivity and 73.68% specificity for detecting malignancy. CONCLUSION: Preoperative serum inhibin levels in women with ovarian tumors are useful in the prediction of malignancy especially when combined with sonography.

Direct visual inspection of the cervix for the detection of premalignant lesions.

OBJECTIVE: To assess the feasibility and performance of direct visual inspection (DVI) of the cervix as a primary tool for the detection of premalignant lesions of the cervix (HPV/CIN 1 and CIN 2,3). SETTING: The early cancer detection unit at the Ain Shams University Maternity Hospital in Cairo, Egypt. SUBJECTS AND METHODS: The study included 2049 women. Cervical smears were obtained from all women for cytologic evaluation followed by direct visual inspection (DVI) of the cervix after painting with 5% acetic acid. Women whose smear reports showed abnormal cells suggestive of squamous intraepithelial lesion (SIL) or human papillomavirus (HPV) infection or those who showed abnormalities or acetowhite areas on direct visual inspection subsequently were referred for colposcopy and biopsy when appropriate. Colposcopy also was performed for women with negative DVI and negative smears if they had contact bleeding or chronic per vaginal discharge. RESULTS: Mean (SD) age of women included in the study was 39.9 (10.2) years with their mean (SD) parity 2.9 (1.1). Results of DVI were normal in 1916 women (93.4%) and showed abnormal acetowhite appearance in 133 (6.6%) women. There were 458 (22.4%) colposcopic examinations and 130 biopsies (6.34%) were carried out, picking up 83 cases of premalignant lesions (4.0%). Premalignant lesions were 80 HPV/CIN 1 and CIN 2,3. Direct visual inspection detected 71 of the 83 premalignant lesions (sensitivity, 85.5%; specificity, 96.8%; positive predictive value, 52.6%). Direct visual inspection missed one of the three samples showing CIN 2,3. Cervical cytologic analysis showed abnormal cells in 60 (2.9%) and identified only 14 of the premalignant lesions (sensitivity, 16.9%; specificity, 97.8%; positive predictive value, 23.3%). Twelve of the premalignant lesions had positive smear results and a negative DVI, with none of them being of a high grade. CONCLUSIONS: Direct visual inspection is feasible and had superior sensitivity compare with cervical cytologic analysis in detecting premalignant lesions of the cervix. Direct visual inspection can be used as a primary screening tool with a satisfactory low biopsy rate in low-resource settings or where cytologic services are suboptimal.