Ziad Hilal

Fetal electrocardiographic measurements in the assessment of fetal heart rate variability in the antepartum period

This study examines signal availability in fetal electrocardiogram (FECG) beat-to-beat acquisition and the accuracy of fetal heart rate variability (HRV) analysis in the clinical setting using a commercially available FECG monitor. Signal availability was examined in 130 FECG recordings of 0.3-17.5 h duration collected in 63 fetuses (25th-42nd week of gestation) under uncontrolled conditions. Identification of R-peaks demonstrated a signal loss of 30% ± 24% with 3.6 ± 1.7 signal gaps per minute. Median duration of the gaps within a recording was 1.8 ± 0.2 s. Per hour of recording, 1.8 ± 2.1 episodes of 5 min of uninterrupted data were found. Signal availability improved with gestational age and was poorer in women with high body-mass index. Fetal HRV between weeks 36-42 was examined on the basis of 5 min RR-interval episodes obtained under controlled quiet conditions in 55 FECG compared to 46 high quality fetal magnetocardiograms. There were no differences in RR-interval duration, its standard deviation and low frequency power. However, various measures of short-term HRV were significantly higher in the FECG data: root mean square of successive differences (10.0 ± 1.8 versus 6.6 ± 3.0 ms, p < 0.001, high frequency spectral power (24 ± 12 versus 13 ± 13 ms(2), p < 0.001) and approximate entropy (0.86 ± 0.16 versus 0.73 ± 0.24, p = 0.007). We conclude that, in spite of considerable signal loss, FECG recordings can accurately estimate heart rate and its overall variance. However, measures that quantify short-term beat-to-beat HRV will be compromised due to possible recurring inappropriate detection of single R-peaks.

Intraperitoneal cisplatin and doxorubicin as maintenance chemotherapy for unresectable ovarian cancer: a case report

BackgroundPrimary advanced, unresectable ovarian cancer (OC) is treated with palliative systemic chemotherapy. Intraperitoneal chemotherapy may be an alternative local maintenance therapy.Case presentationA 75 year old woman with laparoscopically and histologically confirmed unresectable OC was treated with 13 cycles of intraperitoneal cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 over 2 years using laparoscopic pressurized intraperitoneal aerosol chemotherapy (PIPAC). Objective tumor response (tumor regression on histology, stable disease on repeated video-laparoscopy and peritoneal carcinomatosis index) was noted. No Common Terminology Criteria for Adverse Events (CTCAE) > grade 3 were observed. EORTC QLQ-C30 quality of life measurements were stable throughout the therapy.ConclusionsRepeated intraperitoneal chemotherapy with cisplatin and doxorubicin applied as PIPAC may be an effective maintenance treatment in women with primary advanced, unresectable OC.

A randomized comparison of video demonstration versus hands-on training of medical students for vacuum delivery using Objective Structured Assessment of Technical Skills (OSATS)

Background: To compare medical students’ skills for vaginal operative delivery by vacuum extraction (VE) after hands-on training versus video demonstration. Methods: We randomized medical students to an expert demonstration (group 1) or a hands-on (group 2) training using a standardized VE algorithm on a pelvic training model. Students were tested with a 40-item Objective Structured Assessment of Technical Skills (OSATS) scoring system after training and 4 days later. OSATS scores were the primary outcome. Performance time, self-assessment, confidence, and global rating scale were secondary outcomes. We assessed the constructive validity of OSATS in this VE model comparing metric scores of experts and students. Results: In all, 137 students were randomized. OSATS scores were higher in group 2 (n = 63) compared with group 1 (n = 74) (32.89 ± 6.39 vs 27.51 ± 10.27, respectively; P < 0.0001). Global rating scale (1.49 ± 0.76 vs 2.33 ± 0.94, respectively; P < 0.0001), confidence (2.22 ± 0.75 vs 3.26 ± 0.94, respectively; P = 0.04), self-assessment (2.03 ± 0.62 vs 2.51 ± 0.77, respectively; P < 0.0001), and performance time (38.81 ± 11.58 seconds vs 47.23 ± 17.35 seconds, respectively; P = 0.001) also favored group 2. After 4 days, this effect persisted with OSATS scores still being significantly higher in group 2 (30.00 ± 6.50 vs 25.59 ± 6.09, respectively; P = 0.001). The assessed OSATS scores showed constructive validity. In a multiple linear regression analysis, group assignment independently influenced OSATS scores, whereas sex, handedness, sports activities, and type of curriculum were not independently associated with OSATS scores. Conclusions: Hands-on training is superior to video demonstration for teaching VE on a pelvic model.

Dynamic changes of tumor gene expression during repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with peritoneal cancer

BackgroundIntraperitoneal chemotherapy is used to treat peritoneal cancer. The pattern of gene expression changes of peritoneal cancer during intraperitoneal chemotherapy has not been studied before. Pressurized intraperitoneal aerosol chemotherapy is a new form of intraperitoneal chemotherapy using repeated applications and allowing repeated tumor sampling during chemotherapy. Here, we present the analysis of gene expression changes during pressurized intraperitoneal aerosol chemotherapy with doxorubicin and cisplatin using a 22-gene panel.MethodsTotal RNA was extracted from 152 PC samples obtained from 63 patients in up to six cycles of intraperitoneal chemotherapy. Quantitative real-time PCR was used to determine the gene expression levels. For select genes, immunohistochemistry was used to verify gene expression changes observed on the transcript level on the protein level. Observed (changes in) expression levels were correlated with clinical outcomes.ResultsGene expression profiles differed significantly between peritoneal cancer and non- peritoneal cancer samples and between ascites-producing and non ascites-producing peritoneal cancers. Changes of gene expression patterns during repeated intraperitoneal chemotherapy cycles were prognostic of overall survival, suggesting a molecular tumor response of peritoneal cancer. Specifically, downregulation of the whole gene panel during intraperitoneal chemotherapy was associated with better treatment response and survival.ConclusionsIn summary, molecular changes of peritoneal cancer during pressurized intraperitoneal aerosol chemotherapy can be documented and may be used to refine individual treatment and prognostic estimations.

Nutritional status, cachexia, and anorexia in women with peritoneal metastasis and intraperitoneal chemotherapy: a longitudinal analysis

Objective To describe the nutritional status of women with peritoneal metastasis (PM) from recurrent ovarian, fallopian, or peritoneal cancer and to assess longitudinal variations of the cachexia-anorexia syndrome (CAS) during palliative pressurized intraperitoneal aerosol chemotherapy (PIPAC). Methods Nutritional assessment included body mass index (BMI), bioelectrical impedance analysis (BIA), and blood chemistry. CAS presence/absence was recorded before and during repeated cycles (1–11) of PIPAC. Results Eighty-four patients with peritoneal cancer (n=5) or PM from recurrent ovarian (n=77) or fallopian tube (n=2) cancer were included. At baseline, resting metabolism (RM) (1,432±172 kcal/day), visceral fat level (7.5±3.2), skeletal muscle mass (27.2%±4.6%), upper arm circumference (27.9±4.6 cm), lower leg circumference (35.1±3.9 cm), serum parameters (albumin [3.5±0.7 g/dL], total protein [6.3±0.9 g/dL], and transferrin [202±60 mg/dL]) were below normal limits. C-reactive protein (CRP) (4.3±6.8 mg/dL), caliper body fat (35.7%±6.3%), and total body fat mass (35.6%±8.5%) were above normal limits. Nineteen/84 (23%) patients had CAS at baseline. Deterioration or stabilization/improvement of CAS was observed in 9/55 (16.4%) and 46/55 (83.6%) patients with follow-up data, respectively. Baseline body fat mass, visceral fat level, skeletal muscle mass, caliper body fat, BMI, ascites, Karnofsky index, RM, and CRP, as well as tumor response were not predictive of CAS deterioration. Conclusion Nutritional decline and onset or deterioration of CAS are difficult to predict. Careful measuring and monitoring of nutritional parameters and CAS in all patients seems to be necessary in order to identify those patients in need of enteral/parenteral nutrition support.

Paget's Disease of the Vulva Treated with Imiquimod: Case Report and Systematic Review of the Literature

Background: Extramammary Pagets disease of the vulva (EPDV) is a rare adenocarcinoma in situ of the vulvar skin and is often resected with involved margins due to its reticular growth pattern. Adjuvant treatment with the immunomodulator imiquimod may be suitable to avoid repeated and mutilating surgery. Case Presentation: We present the case of a 73-year-old woman with EPDV, initially treated with surgical resection and re-resection for involved margins. Final histology revealed Pagets disease of the left vulva with 8 cm in the largest diameter and again involved margins. Subsequently, topical therapy with imiquimod 5% cream twice weekly was applied for 3 months. Vulvoscopy and local biopsies confirmed complete remission (CR). Based on a literature search using PubMed and the Cochrane Central Register of Controlled Trials, 21 reports on the therapeutic efficacy of imiquimod in 70 women with EPDV have been published. Pooled rates of CR and partial remission were 71% (50/70) and 16% (11/70), respectively. There were 4 cases of disease progression under imiquimod and the therapy was generally well tolerated with mild to moderate local reactions in >50% of cases. Conclusion: EPDV is a rare genital neoplasia and may be successfully treated with the topical immunomodulator imiquimod. Specifically, adjuvant imiquimod is a feasible and efficacious treatment option for women with involved resection margins after surgery.

Loop Electrosurgical Excision Procedure (LEEP) with or without Intraoperative Colposcopy: A Randomized Trial

BACKGROUND: Loop electrosurgical excision procedure is the standard surgical treatment for cervical dysplasia. Loop electrosurgical excision procedure is advised to be performed under colposcopic guidance to minimize adverse pregnancy outcomes. To date, there is no evidence from randomized trials for this recommendation. OBJECTIVE: We sought to assess the benefits of performing loop electrosurgical excision procedure under colposcopic guidance in women with cervical dysplasia. STUDY DESIGN: In a prospective, randomized trial, we compared loop electrosurgical excision procedure with loop electrosurgical excision procedure performed under direct colposcopic vision in a 1:1 ratio. The primary endpoint was resected cone mass; the secondary endpoints were margin status, fragmentation of the surgical specimen, procedure time, time to complete hemostasis, blood loss, and intraoperative and postoperative complications. A sample size of 87 per group (n = 174) was planned (with an assumed type I error of 0.05 and drop‐out rate of 5%) to achieve 90% power to detect a 25% reduction in cone mass (with an assumed cone mass of 2.5 ± 1.6 g in the control group) using a nonparametric test (Mann‐Whitney U). RESULTS: From October 2016 through December 2017, we randomized 182 women: 93 in the loop electrosurgical excision procedure group and 89 in the loop electrosurgical excision procedure–direct colposcopic vision group. Women undergoing loop electrosurgical excision procedure–direct colposcopic vision had significantly smaller cone specimens than those undergoing loop electrosurgical excision procedure (weight: median 1.86 [interquartile range 1.20–2.72] vs median 2.37 [interquartile range 1.63–3.31] g, respectively, P = .006). Secondary outcome measures did not differ significantly between groups: resection margin status involved vs free margin: 12 (13%) vs 75 (82%) and 11 (12.4%) vs 75 (84.3%); fragmentation no vs yes: 85 (92.4%) vs 7 (7.6%) and 84 (94.4%) vs 5 (5.6%); procedure time: 190 (interquartile range 138–294) and 171 (interquartile range 133–290) seconds; time to complete hemostasis: 61 (interquartile range 31–108) and 51 (interquartile range 30–81) seconds; intraoperative blood loss (&Dgr;hemoglobin): 0.4 (interquartile range 0.2–1.0) and 0.5 (interquartile range 0.1–0.9); complication rate: 6 (6.5%) and 2 (2.2%). In a multivariate analysis, study group allocation (P = .021) and parity (P = .028), but not age, body mass index, type of transformation zone, and dysplasia degree independently influenced the amount of resected cone mass. CONCLUSION: Loop electrosurgical excision procedure with intraoperative colposcopy leads to significantly smaller cone specimens without compromising margin status.

Thalidomide and lenalidomide for recurrent ovarian cancer: A systematic review of the literature

The present review aimed to assess the safety and efficacy of thalidomide and lenalidomide, two immunomodulatory drugs with anti-angiogenic properties, in women with recurrent ovarian, fallopian tube, and primary peritoneal cancer. A systematic review of the literature was conducted whereby Medline and the Cochrane Central Register of Controlled Trials were searched using terms associated with thalidomide, lenalidomide, and recurrent ovarian, fallopian tube and primary peritoneal cancer. Published English language case reports, trials and studies that described the safety and efficacy of thalidomide or lenalidomide alone, or in combination with other drugs were reviewed. A total of 16 clinical studies involving 394 patients treated with thalidomide (n=188), lenalidomide (n=77) and 129 controls were identified, including five case reports (n=6), three case series (n=45), two phase I trials (n=27), four phase II trials (n=109), and two randomized phase III trials (n=207). In a pooled analysis of thalidomide investigated as a single drug, the overall clinical benefit rate was 43% (43/99) with a mean time to progression of 5.6 months. The response rate (complete response + partial response) was 25%. In a phase III trial, the combination of thalidomide and topotecan significantly increased the overall response rate compared with topotecan alone [14/30 (47%) vs. 8/39 (21%)]. In another phase III trial involving women with asymptomatic biochemical recurrence, compared with tamoxifen, thalidomide was not more effective. Lenalidomide was investigated in three phase I trials and in one phase II trial with an overall clinical benefit rate of 52% (34/65), and a mean time to progression of 4.6 months. The response rate (complete response + partial response) was 6%. Systemic toxicity of both drugs was noted in >77% of patients with pneumonitis/pneumonia, fatigue, neuropathy and venous thromboembolism reported as the most common side effects. Thalidomide and lenalidomide are moderately active in recurrent ovarian cancer. Thalidomide possesses synergistic effects with topotecan. The toxicity of both drugs is considerable and there is a greater amount of data available for thalidomide compared to lenalidomide.

Accuracy of intrapartum fetal blood gas analysis by scalp sampling: A retrospective cohort study

Abstract Fetal blood gas analysis (FBGA) using scalp blood is commonly used to identify serious fetal distress. However, there is a lack of data regarding its accuracy and reliability. The aim of this study was to determine the positive predictive value (PPV) and negative predictive value (NPV) of FBGA for predicting postpartum acidosis in case of nonreassuring fetal heart rate tracings (NRFHRT). To this end, we conducted a retrospective cohort study of singleton term deliveries with NRFHRT according to Fédération Internationale de Gynécologie et d’Obstétrique and Fisher cardiotocography scores undergoing FBGA in a university hospital. The PPV and NPV of FBGA regarding neonatal acidosis (defined as a pH value ⩽ 7.15 in arterial or venous umbilical cord blood) and Apgar scores indicating neonatal depression (defined as a 5-min Apgar score ⩽5) were evaluated. Multivariate analysis was used to determine the influence of cardiotocography variations and the time delay between FBGA and delivery on the accuracy of FBGA. We analyzed 343 deliveries with NRFHRT. In 32 (9%) of these cases, fetal acidosis was confirmed by a postpartum umbilical cord blood pH value ⩽ 7.15. In 308/343 (90%) cases, FBGA identified NRFHRT as false positive (as confirmed by nonacidotic postpartum pH values) and thus avoided unnecessary interventions such as operative delivery. The overall test accuracy of FBGA was 91%. FBGA accurately predicted postpartum cord blood pH values with a margin of ±0.2 in 319/343 (93%) cases. On the other hand, the false negative rate of FBGA was 8% (29/343). The PPV and NPV of FBGA for predicting postpartum acidosis were 50% and 91%, respectively. The sensitivity was 9% and the specificity was 99%. In a multivariate logistic regression analysis, maternal body mass index (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.01–1.17; P = .029) and cardiotocography variations (OR 0.80; 95% CI 0.66–0.98; P = .029) independently affected the predictive value of FBGA. The PPV of FBGA regarding neonatal depression according to Apgar scores was low with only 17%. We conclude that FBGA may be used in clinical practice to rule out, but not to rule in, neonatal acidosis in parturients with NRFHRT. It can avoid unnecessary interventions such as cesarean section or operative vaginal delivery in up to 90% of cases, but cannot reliably detect fetal acidosis.

Efficacy of Monsel Solution After Cervical Biopsy: A Randomized Trial.

Objectives To estimate the efficacy and side effects of Monsel solution for hemostasis after cervical punch biopsy. Methods In a prospective, randomized trial, we compared application of Monsel solution versus a “wait and see” approach in women undergoing cervical punch biopsies in a 1:1 ratio. The primary end point was vaginal bleeding (VB) after 15 minutes measured by scoring a sanitary pad with a 5-level pictogram. Secondary end points were VB after 3, 6, and 24 hours (5-level pictogram), subjective estimation of overall VB during 24 hours, pain after 15 minutes and subjective estimation of overall pain after 24 hours, and overall satisfaction after 24 hours (11-level visual analogue scale). Results One hundred forty-five women were randomized between July 2015 and January 2016. Mean objective VB scores after 15 minutes in 75 women with Monsel solution were 1.2 ± 0.6 compared with 1.8 ± 1.0 in 70 women without Monsel solution (P < 0.001). The secondary end points VB after 3 and 6 hours, but not after 24 hours, were also in favor of Monsel solution (2.1 ± 1.1 vs 2.9 ± 1.2; P < 0.001; 1.6 ± 0.7 vs 2.2 ± 1.0; P < 0.001; 1.6 ± 0.9 vs 1.7 ± 0.9; P = 0.4, respectively). Subjective estimation of overall VB during 24 hours was lower for Monsel solution (23.2 ± 15.8 vs 35.9 ± 19.5; P < 0.001), but pain after 15 minutes, overall pain, and overall satisfaction were not significantly different between groups (19.2 ± 14.4 vs 17.9 ± 16.2; P = 0.3; 20.7 ± 15.8 vs 20.1 ± 18.0; P = 0.5; and 44.1 ± 21.5 vs 43.6 ± 23.2; P = 0.9, respectively). Conclusions Application of Monsel solution significantly reduces bleeding for 6 hours after cervical biopsy but does not affect overall pain or overall satisfaction.