Gene expression of iron transporters, markers of vascularization and structural integrity in placenta of mothers with and without anemia.

OBJECTIVE: To compare the mRNA expression of placental iron transporters (TfR-1 and FPN), markers of placental vascularization (VEGF and sFLT1) and marker of structural integrity (LMN-A) in term women with and without iron deficiency anemia. MATERIALS AND METHODS: A total of 30 pregnant women were enrolled; 15 cases of iron deficiency anemia (Hb 7-10.9 gm/dL) and 15 gestational age matched healthy controls (Hb ≥ 11 gm/dL). Peripheral venous blood was collected for assessment of hemoglobin levels and serum iron profile. Placental tissue was used for assessing the mRNA expression of TfR-1, FPN, VEGF, sFLT-1 and LMN-A via real time PCR. RESULTS: Placental expression of TfR-1, VEGF and LMN-A was increased in pregnant women with anemia compared to healthy pregnant controls. Placental expression of sFLT-1 was decreased in pregnant women with anemia compared to healthy pregnant controls. There was no change in the placental expression of FPN. CONCLUSION: The increased expression of TfR-1, VEGF and LMN-A in cases of iron deficiency anemia are most likely to be compensatory in nature to help maintain adequate fetal iron delivery. WHAT DOES THIS STUDY ADDS TO THE CLINICAL WORK: Compensatory changes in the placenta aimed at buffering transport of iron to the fetus are seen in pregnant women with anemia compared to healthy pregnant controls.

Weight-based oxytocin infusion for preventing uterine atony during caesarean delivery in non-labouring patients: A dose-response study.

Postpartum haemorrhage remains a significant cause of maternal morbidity and mortality with the commonest reason being uterine atony. For prevention of uterine atony during caesarean delivery, oxytocin is advocated as a first line drug. There is however no published data regarding utility of a weight-based oxytocin infusion. The present study evaluated dose-response relationship for oxytocin infusion when used as weight-based regimen. A total of 55 non-labouring patients without risk factors for uterine atony and scheduled for caesarean delivery under spinal anaesthesia were enrolled. Randomization was done to receive oxytocin infusion in a dose of 0.1, 0.15, 0.2, 0.25 or 0.3 IU kg-1  h-1 (n = 11 each), initiated at the time of cord clamping and continued until the end of surgery. Successful outcome was defined as attaining an adequate uterine response at 4 min of initiation of infusion and maintained till end of surgery. Oxytocin associated hypotension, tachycardia, ST-T changes, nausea/vomiting, flushing and chest pain were also observed. A significant linear trend for adequate intraoperative uterine tone was seen with increasing dose of weight-based oxytocin infusion (P < 0.001). The effective dose in 90% population (ED90) was 0.29 IU kg-1  h-1 (95% CI = 0.25-0.42). Amongst the oxytocin associated side effects, a significant linear trend was seen between increasing dose of oxytocin infusion and hypotension as well as nausea/vomiting (p = 0.016 and 0.023 respectively). Thus, oxytocin infusion during caesarean delivery may be used as per the patient's body weight.

Friend or foe? The prognostic role of endometriosis in women with clear cell ovarian carcinoma. A UK population-based cohort study.

PURPOSE: The prognostic role of endometriosis amongst women with ovarian clear cell carcinoma (OCCC) remains debatable. The aim of this study was to ascertain the effect of endometriosis on the prognosis of OCCC. METHODS: A retrospective review of the medical records of 94 women diagnosed and treated for OCCC at a tertiary gynaecological cancer centre in the UK, spanning the period 2010-2019. Women were divided into two groups according to the presence of endometriosis. Clinico-pathological characteristics, progression-free survival (PFS) and overall survival (OS) were collated between the two groups. RESULTS: Forty-six cases of endometriosis-free OCCC (Ef-OCCC) were collated with 48 cases of endometriosis-related OCCC (Er-OCCC). There was no significant difference between the two groups regarding age (p-value = 0.2), FIGO stage (p-value = 0.8), residual disease (RD) (p-value = 0.07), adjuvant chemotherapy agent (p-value = 0.4) or chemo-resistance (p-value = 0.9). The presence of endometriosis did not significantly affect either OS or PFS. The median OS in the Ef-OCCC and Er-OCCC was 55.00 (95% CI 32.00-189.00) and 71.00 (95% CI 47.00-97.00; log rank = 1.35, p-value = 0.2) months. The median PFS in the Ef-OCCC and Er-OCCC group was 39.00 (95% CI 19.00-143.00) and 39.00 (95% CI 19.00-62.00; log rank = 0.7, p-value = 0.4) months. Survival differences between the two groups were not significant after stratification analysis for independent prognosticators. CONCLUSION: Endometriosis was not independently associated with the prognosis of OCCC either in crude analysis or after stratification for stage and RD. Further larger, well-designed prospective studies are warranted to draw firmer conclusions on the intrinsic link between endometriosis and OCCC.

Screening for cervical cancer: Choices & dilemmas.

Cervical cancer is the fourth most common cancer in women in the world. To eliminate cervical cancer by 2030, the World Health Organization has given the target of 70 per cent coverage of twice lifetime screening. A multitude of screening methods are available, including cytology, human papillomavirus (HPV) DNA testing and visual inspection tests. Precision tests, including molecular and protein biomarkers such as DNA methylation, p16 immunostaining, and HPV mRNA testing help to enhance specificity of the screening. Worldwide HPV DNA testing with or without cytology is used as a screening method of choice, while in resource-poor settings, visual inspection tests are recommended. The major hurdle is a uniform and systematic implementation with a recall method in the population. Besides, controversies still exist regarding strategies to manage HPV-positive women and developing guidelines to screen the vaccinated population.

Role of Survivin and p53 Expression in Response of Primary Culture of Ovarian Cancer Cells to Treatment With Chemotherapeutic Agents.

BACKGROUND: Ovarian cancer is associated with a high relapse rate and is the fifth leading cause of cancer deaths in women. The genetic profile of a tumor is responsible for deciding response to chemotherapeutic agents. In this study, we investigate the relation between survivin and p53 expression and response to chemotherapeutic agents of primary cultures of ovarian cancer cells established from ascitic fluid. MATERIALS AND METHOD: Ascitic fluid and Dulbecco's modified Eagle medium was mixed in equal proportion in culture flasks and incubated to establish primary culture. The cells were treated with different combinations of carboplatin and paclitaxel with and without survivin small interfering RNA transfection. Cell survival was estimated by MTT assay. Survivin and p53 expression was quantified by real-time polymerase chain reaction. RESULTS: Out of 19 ascitic fluid samples, 13 primary cultures of ovarian cancer cells were established. The half maximal inhibitory concentration doses of carboplatin (≥70 µg/mL) and paclitaxel (≥18 µg/mL) were high for 10/13 and 5/13 patients, respectively. Survivin messenger RNA expression was significantly downregulated on treatment with carboplatin (100 µg/mL), paclitaxel (12.5 µg/mL), and a combination of carboplatin (50 µg/mL) and paclitaxel (6.25 µg/mL). Only paclitaxel-treated ovarian cancer cells showed decrease in expression of p53. Survivin small interfering RNA increased sensitivity of the primary cultures to chemotherapeutic agents. CONCLUSIONS: The present study highlights the fact that establishing primary cultures from ascitic fluid may help to develop personalized treatment regime for individual patients based on their molecular profile. Our study also shows that supplementing taxols drugs with survivin inhibitors may prove to be beneficial in the treatment of ovarian cancer patients.

Establishment of Primary Cell Culture From Ascitic Fluid and Solid Tumor Obtained From Epithelial Ovarian Carcinoma Patients.

OBJECTIVE: Ovarian cancer is the seventh leading cause of cancer death worldwide. This is mainly due to late diagnosis and high rate of relapse and resistance following chemotherapy. In the present study, we describe simple and cost-effective method to establish primary culture from ascitic fluid and solid tumor obtained from epithelial ovarian carcinoma patient, which may provide a better tool for in vitro testing of drug sensitivity and designing individualized treatment protocol. METHODS: Complete Dulbecco modified Eagle medium (DMEM) was prepared by supplementing DMEM with 10% fetal bovine serum and antibiotics (ciprofloxacin and amphotericin B). Establishment of primary culture of ovarian cancer cells from ascites fluid and solid tumor was done by using complete DMEM media. RESULTS: Primary cultures of ovarian cancer cells were established from ascitic fluid and solid tumor tissue. Of the 7 ascitic fluid samples, we were able to establish 5 primary cultures of ovarian cancer cells. All the 7 samples were diagnosed as serous papillary adenocarcinoma. Some fibroblasts were also attached to culture flask on day 4; they were removed by exposing them to trypsin for a brief period. On day 7, grape-like clusters were visualized under inverted microscope. The cells became confluent on the 10th and 11th day and showed cobblestone appearance, which is a hallmark of ovarian cancer cells. Senescent irregularly shaped cells that have ceased dividing were seen after 8 to 10 passages. CONCLUSION: This study highlights the fact that establishing primary cultures from ascitic fluid or solid tumor tissue may help us to understand the molecular profile of the cancer cells, which allow us to select the best chemotherapeutic agent for ovarian cancer patients and thus take a step toward patient-tailored therapy so that patients are not exposed to drugs to which they are not likely to respond.

Adolescent ovarian masses: A retrospective analysis.

A retrospective study was conducted to review incidence, clinical practice, surgical management and histology of adolescent ovarian masses in order to audit and improve future practices. Complete hospital records of all adolescents between 10 and 20 years who had undergone surgery for ovarian masses were analysed between November 2006 to 2014. Parameters analysed were age, clinical features, diagnosis, operative procedure and histopathology. Ninety-four patients were included in the study and among them, 37 had non-neoplastic masses, 30 had benign neoplasms while 27 had malignant tumors. The main clinical presentations were abdominal pain (54%) and abdominal mass (41%). Dermoid was the most common benign neoplasm while germ cell tumor was the most common malignant mass; dysgerminoma being the commonest (68%). Malignancy was more common in early adolescence (12 ± 4.8 years) while non-neoplastic masses were seen more frequently in late adolescence (17.7 ± 2.2 years). There was a fair correlation between ultrasound and histopathological diagnosis.

Is nuchal cord justified as a cause of obstetrician anxiety?

PURPOSE: Birth asphyxia leading to acidosis comprises 20-60 % of perinatal mortality. Nuchal cord (NC) is one of the possible causes of birth asphyxia. Majority of fetuses who are antenatally detected to have nuchal cord are able to achieve successful vaginal birth. The purpose of this study was to analyze the effect of nuchal cord on fetal acid base status and perinatal outcome in vaginal deliveries. STUDY DESIGN: 150 parturients were equally divided into three groups after vaginal delivery based on no NC, single and multiple loops. Umbilical cord arterial blood was analyzed for biochemical markers i.e. pH, PO2, SPO2, PCO2, HCO3 (-), standard base excess and lactate for acidosis. Labor complications like abnormal FHR, meconium-stained liquor, prolonged second stage, instrumental vaginal delivery, third stage complications were compared. In neonates, birth weight, Apgar score ≤7 at 5 min, NICU admission and other morbidity and mortality during hospital stay were compared among groups using suitable statistical tests. Above parameters were also compared between tight and loose loops. RESULT: Nuchal cord groups had significantly higher frequency of labor complications than no NC group, especially tight loops. Neonates with NC had significantly higher frequency of meconium-stained liquor, Apgar score ≤7 at 5 min, deranged biochemical markers, NICU transfer. However, none of the neonate had pH in acidosis range and majority were discharged in healthy condition. CONCLUSION: Patients with NC are likely to have uneventful labor and delivery as cord compression is transient and most fetuses are able to compensate for reduce umbilical blood flow. Routine antenatal ultrasound scan is not advisable, as mode of delivery and labor management does not change with detection of NC antenatally. Therefore, vaginal delivery with routine labor protocol can be allowed in cases of nuchal cord.

Weight-based versus fixed dose oxytocin infusion for preventing uterine atony during cesarean section in laboring patients: A randomized trial.

OBJECTIVE: We compared efficacy of weight-based (0.4 IU/kg/h) versus fixed-dose (34 IU/h) oxytocin infusion during cesarean section. METHODS: The oxytocin infusion in either group (n = 32 each) was initiated upon cord clamping. Primary outcome measure was adequacy of uterine tone at 4 min after initiating oxytocin infusion. Oxytocin associated side effects were also observed. RESULTS: Significantly less oxytocin was used with the weight-based versus fixed-dose regimen (16.3 [11.2-22.4] IU vs 20.4 [15.8-26.9] IU; P = 0.036). Incidence of adequate uterine tone was clinically greater but not significantly different with the weight-based versus fixed-dose regimen (81.3% vs 71.9%; P = 0.376). The weight-based regimen was associated with clinically lesser, although not statistically significant need for rescue oxytocin (25% vs 46.9%; P = 0.068) and additional uterotonic (9.4% vs 15.6%; P = 0.708); as well as oxytocin associated side effects (hypotension [34.4% vs 46.9%; P = 0.309], nausea/vomiting [18.8% vs 40.6%; P = 0.055], and ST-T changes [0% vs 3.1%; P = 1.000]). CONCLUSION: Weight-based oxytocin was not significantly different from the fixed-dose regimen in terms of uterotonic efficacy or associated side-effects, despite significantly lower doses being used. Use of weight-based oxytocin infusion (0.4 IU/kg/h) can be considered in clinical practice. TRIAL REGISTRATION: Clinical Trial Registry of India (ctri.nic.in, number. CTRI/2021/01/030642).

Chromocolposcopy with fluorescein sodium for detection of premalignant and malignant lesions of the cervix: A cross-sectional study.

OBJECTIVE: The aim of the study was to explore the utility of fluorescein sodium (FNa) as a contrast agent for colposcopy to detect premalignant and malignant lesions of cervix. The primary objective was to determine and compare the percentage detection of premalignant and malignant lesions of FNa and acetic acid (AA) positive areas. METHODS: This study included 120 screen positive women who underwent colposcopy using both 3% AA and FNa (0.06%). Observations for FNa staining were made under blue filter and directed biopsies were taken from acetowhite and fluorescent green areas. Benign lesions were considered as disease-negative and low grade squamous intraepithelial lesions (LSIL), high grade SIL (HSIL), and invasive cancer were considered as disease-positive. Correlation between histopathology and FNa and AA was determined by Kappa statistics. RESULTS: The mean age was 39.59 ± 10.73 years and median parity was 2. Out of 120 patients, 57 had benign lesions, 18 had LSIL, 33 had HSIL and 12 had invasive carcinomas. Sensitivity was 98.41% versus 64.91% respectively and specificity was 85.71% versus 35.09% respectively with FNa and AA. Diagnostic accuracy of FNa and AA was 82.50% versus 61.60%. There was good agreement between FNa staining and final histopathology and fair agreement between AA application and HPE (κ = 0.643 vs 0.213, P < 0.001). CONCLUSION: Using FNa as a contrast agent during colposcopy results in greater accuracy for detection of premalignant and malignant lesions of the cervix as compared to AA.

Abnormally invasive placenta: changing trends in diagnosis and management.

Trends in patient profile, clinical presentation, diagnosis, management options and outcome of abnormally invasive placenta (AIP) were retrospectively evaluated at a tertiary care centre from 2001 to 2010. AIP was diagnosed when confirmed by ultrasound or MRI, when complete manual removal of placenta was not possible or when histological confirmation was achieved in a hysterectomy specimen. The first and second halves of the time period were compared. The total number of cases was 56 and the incidence increased significantly in the second half. Main risk factors were placenta previa and previous cesarean section. Antenatal diagnosis by ultrasound was made in 72% in the second half, compared with 35% in the first half (p = 0.009). Maternal mortality was 29% in the first half and 21% in the second half. Hysterectomy was the mainstay in management; elective procedures being significantly higher in the second half.

Common Medical Devices with Uncommon Complications.

Medical devices and materials commonly used in management of common gynecological conditions or during surgical procedures may present with acute or chronic complications due to incorrect application, improper use and lack of follow up. We present two interesting cases highlighting this problem. A strong index of suspicion is very crucial in early diagnosis and successful management.

A novel technique of vagino-hysteroscopy using alginate gel interface: A proof of concept study.

OBJECTIVE: To compare the feasibility of vagino-hysteroscopy using alginate gel Interface (VAGI) with conventional vaginoscopic hysteroscopy (CVH). METHODS: Thirty women undergoing diagnostic vagino-hysteroscopy were randomly allocated into Group I (VAGI): Alginate occluder was used at introitus to facilitate hydrodistension during hysteroscopy; or Group II: Underwent no-touch hysteroscopy. Primary outcome was feasibility, defined as successful visualization of uterine cavity. Secondary outcomes included operative time, hydrostatic pressures for optimum visualization, pain experienced by patient on visual analog scale, maneuverability and surgeon satisfaction. Data analysis was performed using χ2 and Fisher exact tests for qualitative variables and Student t test for quantitative variables. RESULTS: VAGI was significantly better than CVH (80% vs. 33.3%; relative risk 8, P = 0.025). With VAGI, optimum visualization was achieved at significantly lower pressures at all levels (vagina, P = 0.034; cervix, P = 0.01; uterus, P < 0.001), in less time (P = 0.007), and using less irrigation fluid (P < 0.001). Surgeon satisfaction was significantly higher for VAGI (P = 0.009). Subgroup analysis showed higher likelihood of success of VAGI in women who were premenopausal (P = 0.015), younger than 45 years (P = 0.024), and had a history of vaginal birth (P = 0.03). CONCLUSIONS: VAGI is quicker to perform and provides optimum visualization at much lower pressures than CVH. Use of alginate is patient friendly and yields higher surgeon satisfaction rate.

Iron Profile in Term Small for Gestational Age Infants at 10 Weeks of Age and Correlation With Maternal Iron Profile : A Prospective Cohort Study.

BACKGROUND: Term small for gestational age (SGA) babies are at risk for developing iron deficiency anemia. The association between maternal and infant iron stores is not clear. OBJECTIVE: To assess proportion of term SGA neonates developing iron deficiency anemia by 10 weeks of age, and measure correlation between iron profile and hepcidin of babies at birth and at 10 weeks of age with maternal iron profile. DESIGN: Prospective cohort study conducted from November, 2018 to April, 2020. PARTICIPANTS: 120 term SGA babies and their mothers. INTERVENTION: Hemogram, iron profile and serum hepcidin (every fourth case) estimated in mother, cord blood and baby at 10 weeks. Babies developing anemia at 6 weeks detected by hemogram and ferritin were started on iron supplementation and excluded from the study. OUTCOME: Proportion of babies developing iron deficiency anemia at 10 weeks of age. RESULTS: 35 (29.2%) of 120 term SGA babies developed anemia (hemoglobin <9 g/dL) at 6 weeks. Proportion of infants who developed iron deficiency anemia (hemoglobin <9 g/dL and serum ferritin <40 µ/dL) at 6 and 10 weeks of age was 14.2% and 23.3%, respectively. No significant correlation was found bet-ween hemoglobin, iron and hepcidin of the baby in cord blood and at 10 weeks of age with that of mothers. Serum hepcidin in babies at birth (137.5 ng/mL) were higher than maternal values (128 ng/mL). CONCLUSION: A significant proportion of term SGA infants deve-loped anemia during early infancy, irrespective of maternal iron status.

Extrauterine Adenomyosis Coexistent with Mature Cystic Teratoma: An Extremely Rare Entity.

Extrauterine adenomyosis is a rare entity. We present a case of a 32-year-old female who presented with this rare entity as a large abdominal mass and was a diagnostic and pathological dilemma.

PAX1 Methylation Status in Cervical Scrapes as Novel Diagnostic Biomarker in CIN 2/3 and Invasive Squamous Cell Carcinoma.

Objectives: DNA methylation of paired box-1 (PAX-1) gene has been shown to be a potential biomarker for the detection of high-grade cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer. The objective of this pilot study was to quantify and compare methylation percentage of PAX1 gene in benign cervical lesion, pre-invasive and invasive cervical cancer. Methods: A total of 200 screen positive women (VIA, VILI and Pap test) underwent colposcopy. Cervical scrapes taken were taken and stored for DNA analysis and PAX 1 methylation status. Women with Swede score of 5 or more (n = 98) were biopsied. Cervical scrapes and biopsy were taken from women with obvious cervical growth (n = 14), without prior colposcopy. Sixty women were recruited to the study and allocated into three groups on the basis of histopathology, i.e., benign cervix (Group 1; n = 20), CIN 2/3 (Group 2; n = 20) and invasive cervical carcinoma (Group; n = 20). PAX 1 methylation percentage was calculated from the DNA extracted from the cervical scrapes of the women recruited. Results: The mean PAX1 methylation percentage in benign lesions, CIN 2/3 and invasive cancer was 9.58% (SD ± 2.37%), 18.21% (SD ± 2.67%) and 24.34% (SD ± 4.09%), respectively, with p-value of < 0.001. Conclusions: PAX 1 gene methylation has a promising role in identifying high-grade lesions and invasive cancer.

Dysuria: don't take it lightly.

Dysuria is a very common symptom, which is taken lightly. It can lead to a diagnosis of disseminated Koch's, which if identified early can prevent permanent sequelae.

Rupture of intrapartum unscarred uterus at the fundus: a complication of passive cocaine abuse?

Uterine rupture is a potential obstetric catastrophe. We report a case of a gravida 2 para 1 with intrapartum unscarred uterine fundal rupture. Immediate resuscitation, laparotomy and hysterectomy, was done with maternal survival. History of passive cocaine smoke exposure elicited postoperatively was the possible etiology leading to complete fundal rupture. This case is an eye opener as regards to ill effects of drug abuse even though passive. A careful history of drug abuse must be elicited when the common causes of uterine rupture have been excluded or the rupture site is unusual.

Primary umbilical endometriosis: a rare entity.

Primary umbilical endometriosis accounts for 0.5-1% of extragenital endometriosis. Clinical presentation is typical and treatment involves complete excision. It is important to consider it in differential diagnosis of an umbilical nodule.

Evaluation of frozen section biopsy for fast track diagnosis of endometrial pathology in high-risk women with abnormal uterine bleeding.

OBJECTIVE: To study the accuracy of frozen section biopsy for endometrial pathology in high-risk women with abnormal uterine bleeding (AUB). STUDY DESIGN: A case-control study was conducted between November 2017 to April 2019, a total of 150 women with postmenopausal bleeding, perimenopausal AUB, and high-risk women of age < 40 years with AUB were recruited. All women underwent transvaginal sonography and Doppler, based on age-appropriate endometrial thickness cut-offs 80 women then underwent hysteroscopy. Based on hysteroscopy, women suspicious of malignancy were taken as cases (n = 40) and those with benign findings as controls (n = 40). All cases and controls underwent dilatation and curettage (D & C) with frozen section (FS) and routine histopathology. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR), negative LR, and overall test accuracy of FS were 90.9%, 93.19%, 83.33%, 96.19%, 13.8, 0.1 and 86.25% respectively for diagnosing endometrial hyperplasia and cancer taking histopathology as the gold standard. Correlation between frozen section biopsy and histopathology was highly significant (p < 0.001) on D & C specimens and the level of agreement was good (K = 0.778). CONCLUSION: In women suspicious of malignancy on hysteroscopy, frozen section has high accuracy on D&C specimen and can be used to diagnose endometrial hyperplasia and cancer in an effort to fast-track investigations and work-up for definitive treatment while awaiting final histopathology.