Publications by authors named "Ismail A Al-Badawi"

43 Publications

Vaginal dinoprostone versus placebo for pain relief during intrauterine device insertion: a systematic review and meta-analysis of randomised controlled trials.

Eur J Contracept Reprod Health Care 2021 Mar 11:1-13. Epub 2021 Mar 11.

Department of Obstetrics and Gynecology, HealthPlus Fertility and Women's Health Center, Jeddah, Saudi Arabia.

Objective: To systematically and meta-analytically investigate the efficacy and safety of vaginal dinoprostone versus placebo in pain relief during intrauterine device (IUD) insertion.

Methods: PubMed, Scopus, Web of Science, and Cochrane Library were screened till 1 October 2020. Only randomised placebo-controlled studies were included and assessed for risk of bias. Main outcomes included IUD insertion related pain, patient satisfaction, provider ease of IUD insertion, and side effects. Pooled outcomes were summarised as standardised mean difference (SMD), weighted mean difference (WMD), or risk ratio (RR) with 95% confidence interval (95% CI).

Results: Five studies were included, comprising 862 patients; equally 431 patients received vaginal dinoprostone and placebo. All studies showed an overall low risk of bias. When compared to placebo, dinoprostone significantly correlated with decreased pain at tenaculum placement (SMD = -0.79, 95% CI [-1.43, -0.16],  = 0.01), decreased pain at uterine sounding (SMD = -0.88, 95% CI [-1.54, -0.22],  = 0.009), decreased pain at IUD insertion (SMD = -1.18, 95% CI [-1.74, -0.61],  < 0.001), decreased need for additional analgesia (RR = 0.34, 95% CI [0.22, 0.53],  < 0.001), increased patient satisfaction (SMD = 1.41, 95% CI [0.62, 2.20],  < 0.001), and increased provider ease of IUD insertion (SMD = -1.17, 95% CI [-1.62, -0.73],  < 0.001). Fever was statistically significantly higher in dinoprostone versus placebo group (RR = 3.73, 95% CI [1.47, 9.44],  = 0.006). All other side effects-including nausea, vomiting, shivering, diarrhoea, abdominal cramps, vasovagal attack, uterine perforation, and postprocedural bleeding-did not substantially differ between both groups.

Conclusions: This first ever meta-analysis advocates that dinoprostone compared with placebo is safe, effective, and yields favourable analgesic outcomes during IUD insertion.
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http://dx.doi.org/10.1080/13625187.2021.1891411DOI Listing
March 2021

PD-L1 Expression Is an Independent Marker for Lymph Node Metastasis in Middle Eastern Endometrial Cancer.

Diagnostics (Basel) 2021 Feb 25;11(3). Epub 2021 Feb 25.

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia.

Programmed death ligand 1 (PD-L1) expression in endometrial cancer (EC) tumor cells have been reported in several studies with inconsistent results. Furthermore, there is scarcity of data on the prevalence and prognostic significance of PD-L1 expression in EC from Middle Eastern ethnicity. We aimed to assess PD-L1 expression in a large cohort of Middle Eastern EC and to correlate this with clinico-pathological factors, as well as mismatch repair (MMR) protein status and patients' outcome. PD-L1 expression was investigated using immunohistochemistry on tissue microarray in an unselected cohort of 440 EC. Kaplan-Meier and logistic regression analysis were used to compare the outcome and prognostic factors. PD-L1 expression in tumor tissue was detected in 18.9% (83/440) EC cases with no impact on survival. When stratified for MMR protein status, PD-L1 expression was similar for both MMR deficient and MMR proficient ECs. However, the expression of PD-L1 in tumor cells was significantly associated with type II (non-endometrioid) histology ( = 0.0005) and lymph node metastasis ( = 0.0172). Multivariate analysis showed PD-L1 expression to be an independent risk factor for lymph node metastasis (odds ratio: 2.94; 95% CI: 1.26-6.84; = 0.0123). In conclusion, PD-L1 was strongly associated with non-endometrioid EC and was an independent prognostic marker of lymph node metastasis.
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http://dx.doi.org/10.3390/diagnostics11030394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996603PMC
February 2021

Differential expression of PD-L1 between primary and metastatic epithelial ovarian cancer and its clinico-pathological correlation.

Sci Rep 2021 Feb 12;11(1):3750. Epub 2021 Feb 12.

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Ovarian cancer (OC) is one of the most common gynecologic cancer, which has the worst prognosis and highest mortality rate. The lack of curative treatment and the high relapse rate, especially in advanced OC, continues to present a clinical challenge, highlighting the need for new therapeutic strategies. This study was performed to compare the expression of PD-L1 in primary epithelial ovarian cancer (EOC) and their corresponding peritoneal metastases, as well as to evaluate its correlation with clinico-pathological parameters. In total, 194 treatment naïve paired EOC and peritoneal metastasis were analyzed by immunohistochemistry for PD-L1 expression. Clinico-pathological information was available for all patients. Significant differences in PD-L1 expression were found between primary EOC and peritoneal metastasis (p < 0.0001). We found discordant tumor cell PD-L1 expression between primary tumors and corresponding peritoneal metastasis in 34% (66/194) of cases. Furthermore, PD-L1 expression in peritoneal metastasis samples was significantly associated with adverse prognostic factors, such as high proliferative index (Ki67) (p = 0.0039) and high histologic grade (p = 0.0330). In conclusion, the discordance of PD-L1 expression between primary EOC and corresponding peritoneal metastases suggests that its assessment as a potential biomarker for predicting response to anti-PD-L1 therapy may require analysis of metastatic lesions.
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http://dx.doi.org/10.1038/s41598-021-83276-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881132PMC
February 2021

Intraoperative local injection of uterosacral ligaments with ropivacaine during uterine surgery: A systematic review and meta-analysis of randomized controlled trials.

J Gynecol Obstet Hum Reprod 2021 Feb 3;50(8):102077. Epub 2021 Feb 3.

Department of Obstetrics and Gynecology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Electronic address:

Aim: To perform a systematic review and meta-analysis of all randomized controlled trials that examined the efficacy of intraoperative local injection of the uterosacral ligaments with ropivacaine on postoperative pain and opioids consumption in patients undergoing uterine surgery for hysterectomy/myomectomy.

Methods: PubMed, Scopus, Web of Science and Cochrane Library databases were screened from inception to September 5th, 2020. We appraised the risk of bias using the Cochrane's risk of bias tool. Resting postoperative pain scores and cumulative consumption of postoperative opioids were regarded as continuous data, analyzed using the inverse variance method and reported as standardized mean difference (SMD) and weighted mean difference (MD), respectively, with 95 % confidence intervals (95 % CIs).

Results: Five studies met the inclusion criteria comprising 230 patients (117 and 113 patients received ropivacaine and placebo, respectively). The studies had an overall low risk of bias. Resting postoperative pain scores were not significantly different between both groups at 2 h (SMD = -0.30, 95 % CI [-0.70, 0.11], p = 0.15), 12 h (SMD = 0.04, 95 % CI [-0.26, 0.37], p = 0.81) and 24 h (SMD = -0.06, 95 % CI [-0.32, 0.20], p = 0.68). However, the ropivacaine group had significantly reduced cumulative opioid consumption during the first 24 h postoperatively (MD = -9.07, 95 % CI [-14.47, -3.66], p = 0.001).

Conclusion: Intraoperative local infiltration of uterosacral ligaments with ropivacaine is technically feasible and significantly reduces postoperative opioid consumption in women undergoing gynecologic surgery of the uterus.
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http://dx.doi.org/10.1016/j.jogoh.2021.102077DOI Listing
February 2021

Preoperative anemia predicts poor prognosis in patients with endometrial cancer: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2021 Mar 27;258:382-390. Epub 2021 Jan 27.

Department of Obstetrics and Gynecology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Aim: To systematically and meta-analytically pool the existing evidence regarding the prognostic impact of preoperative anemia (hemoglobin level <12 mg/dl) in patients with endometrial cancer.

Methods: Four (PubMed, Embase, Scopus and Web of Science) databases were searched from inception to 20-August-2020. We assessed the risk of bias using the Newcastle-Ottawa Scale. We estimated the pooled prevalence of preoperative anemia in the included studies. We pooled odds ratios (ORs) and hazard ratios (HRs) with their 95 % confidence intervals (95 % CIs) to evaluate the correlation between preoperative anemia and its impact on clinicopathologic parameters and survival outcomes. Analyses were performed under random- or fixed-effects meta-analysis models depending on data heterogeneity.

Results: Seven studies met the inclusion criteria comprising 1495 patients with endometrial cancer. Nearly all studies had low risk of bias. The pooled prevalence of preoperative anemia was 26.5 % (95 % CI: 18.6%-36.2%). Preoperative anemia significantly correlated with advanced FIGO stage III-IV (OR = 5.14, 95 % CI [3.36, 7.86], p < 0.00001), ≥50 % myometrial invasion (OR = 1.95, 95 % CI [1.36, 2.78], p = 0.0003), lymph node metastasis (OR = 4.46, 95 % CI [2.39, 8.30], p < 0.00001), non-endometrioid histology (OR = 3.25, 95 % CI [1.89, 5.60], p < 0.0001), adnexal involvement (OR = 5.88, 95 % CI [3.05, 10.23], p < 0.001), cervical involvement (OR = 2.91, 95 % CI [1.65, 5.11], p = 0.0002), positive peritoneal cytology (OR = 3.24, 95 % CI [1.41, 7.44], p = 0.006), preoperative thrombocytosis (OR = 6.66, 95 % CI [3.05, 14.52], p < 0.00001) and lymphovascular space invasion (OR = 3.50, 95 % CI [1.82, 6.74], p = 0.0002). High tumor grade II-III was increased in patients with preoperative anemia, yet this effect was not statistically significant (OR = 2.12, 95 % CI [0.97, 4.66], p = 0.06). Consistently, the five-year overall survival (OS) and disease-free survival (DFS) rates were significantly lower in patients with preoperative anemia when compared to those without preoperative anemia. Pooled HR showed that preoperative anemia was significantly associated with reduced DFS at univariate (HR = 3.22, 95 % CI [1.28, 8.11], p = 0.01) and multivariate (HR = 1.02, 95 % CI [1.00, 1.05], p = 0.03) analyses.

Conclusion: Preoperative anemia predicts poor clinicopathologic and survival outcomes in patients with endometrial cancer.
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http://dx.doi.org/10.1016/j.ejogrb.2021.01.038DOI Listing
March 2021

Ropivacaine versus lidocaine infiltration for postpartum perineal pain: A systematic review and meta-analysis.

J Gynecol Obstet Hum Reprod 2021 Jan 27;50(8):102074. Epub 2021 Jan 27.

Department of Obstetrics and Gynecology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Electronic address:

Aim: To systematically and meta-analytically examine the efficacy of ropivacaine versus lidocaine infiltration for controlling postpartum perineal pain secondary to spontaneous tear or selective episiotomy.

Methods: We searched four databases from inception to 20-September-2020. We included all relevant randomized and nonrandomized studies and assessed their risk of bias. We pooled data as standardized mean difference (SMD), weighted mean difference (WMD), or odds ratio (OR) with 95 % confidence intervals (95 % CIs).

Results: Four studies met the inclusion criteria (one and three studies were nonrandomized and randomized, respectively). There were 405 patients; 205 and 200 patients received lidocaine and ropivacaine, respectively. There was no significant difference between ropivacaine and lidocaine groups with regard to visual analogue scale (VAS) pain scores at suturing (WMD = -0.04, 95 % CI [-0.41, 0.32], P = 0.82), 2 h (SMD = -1.50, 95 % CI [-3.50, 0.50], P = 0.14), and 24 h (SMD = -0.40, 95 % CI [-1.15, 0.34], P = 0.29) post repair of perineal trauma. Proportion of patients with mild VAS pain score ≤3 at 24 h was significantly higher in the ropivacaine group (OR = 4.34, 95 % CI [2.03, 9.29], P < 0.001). Proportion of patients who did not require additional analgesia during the first 24 h post perineal repair did not significantly differ between both groups (OR = 2.44, 95 % CI [0.09, 68.21], P = 0.60). Ropivacaine group achieved higher maternal satisfaction (OR = 7.13, 95 % CI [3.63, 13.99], P < 0.001).

Conclusions: During repair of postpartum perineal trauma, pain efficacy is relatively longer with ropivacaine but safety is not well investigated. High-quality and large-sized studies are needed to consolidate these findings.
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http://dx.doi.org/10.1016/j.jogoh.2021.102074DOI Listing
January 2021

A Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy in Primary Advanced Ovarian Cancer: The First Reported Pilot Experience from Saudi Arabia.

Gulf J Oncolog 2020 Sep;1(34):19-25

College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

Background: Around two thirds of patients with ovarian cancer present to clinical attention with advanced-stage disease in the form of peritoneal carcinomatosis (PC) or distant metastasis, which is correlated with a poor fiveyear overall survival (OS) of less than 20%. The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery (CRS) has been depicted to offer survival benefits in patients with PC arising from primary advanced ovarian cancer. However, no similar study was conducted from Saudi Arabia, specifically, or the Gulf region, generally. The primary aim of this study is to describe our pilot single-institutional experience (feasibility, safety and survival outcomes) with CRS plus HIPEC in managing PC arising from primary advanced ovarian cancer..

Material And Method: A retrospective cross-sectional study was conducted at Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. From January 2016 to July 2019, the medical records of 16 eligible patients were reviewed for clinical, perioperative and survival data. Survival analyses of DFS were calculated according to the Kaplan-Meier estimates method and compared by using two-tailed log-rank test. Statistical significance was regarded as a p value < 0.05.

Results: Cytoreduction completeness CC-0 (optimal) and CC-1 (suboptimal) were achieved in 10 (63%) and six (37%) patients, respectively. The median peritoneal cancer index (PCI) score was 11 (range: 6-18). Nine patients (56%) received combination cisplatin (50 mg/m2) plus doxorubicin (15 mg/m2) as HIPEC regimen whereas the remaining seven patients (44%) received intense single-agent cisplatin (100 mg/m2). No intraoperative morbidity or mortality occurred. Four patients (25%) developed grade III-IV postoperative adverse events based on the Clavien-Dindo surgical complications; no patient developed HIPEC-related renal or hematological toxicities. The median hospital stay was 13 days (range: 11-40). The median follow-up time was 16 months (range: 7-43). The mean OS and DFS were 38.7 months (95% confidence interval [CI]: 31.7-45.6) and 28.4 months (95% CI: 20.7-36.0), respectively. Eleven patients were alive and disease-free (69%). Disease recurrence occurred in five patients (31%). One patient died 30 months after CRS plus HIPEC due to distant brain metastasis. Univariate analysis of parameters related to DFS showed that advanced stage IV disease (p = 0.01), suboptimal CC-1 cytoreduction completeness (p = 0.01) and >11 high PCI score (p = 0.03) were independent factors associated with statistically significant poor DFS.

Conclusion: CRS plus HIPEC is technically feasible, largely morbid-free and correlates with enhanced survival outcomes in patients with primary advanced ovarian cancer.
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September 2020

Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer.

Front Pharmacol 2020 3;11:598880. Epub 2020 Dec 3.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Despite current therapeutic and surgical options, advanced EOC shows poor prognosis. Identifying novel molecular therapeutic targets is highly needed in the management of EOC. Krupple-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in a variety of cancer types. However, its role and expression in EOC is not fully illustrated. Immunohistochemical analysis was performed to assess KLF5 protein expression in 425 primary EOC samples using tissue microarray. We also addressed the function of KLF5 in EOC and its interaction with signal transducer and activator of transcription 3 (STAT3) signaling pathway. We found that KLF5 overexpressed in 53% (229/425) of EOC samples, and is associated with aggressive markers. Forced expression of KLF5 enhanced cell growth in low expressing EOC cell line, MDAH2774. Conversely, knockdown of KLF5 reduced cell growth, migration, invasion and progression of epithelial to mesenchymal transition in KLF5 expressing cell lines, OVISE and OVSAHO. Importantly, silencing of KLF5 decreased the self-renewal ability of spheroids generated from OVISE and OVSAHO cell lines. In addition, downregulation of KLF5 potentiated the effect of cisplatin to induce apoptosis in these cell lines. These data reveals the pro-tumorigenic role of KLF5 in EOC and uncover its role in activation of STAT3 signaling pathway, suggesting the importance of KLF5 as a potential therapeutic target for EOC therapy.
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http://dx.doi.org/10.3389/fphar.2020.598880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793801PMC
December 2020

The influence of omega-3 supplementation on vitamin D levels in humans: a systematic review and dose-response meta-analysis of randomized controlled trials.

Crit Rev Food Sci Nutr 2020 Dec 25:1-8. Epub 2020 Dec 25.

Department of Pharmacology, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

Background: Inconsistencies exist with regard to the influence of omega-3 supplementation on 25-hydroxyvitamin D (25(OH)D) levels, which could be attributed to many factors, such as the duration and dose of omega-3 supplementation, and individuals' baseline 25(OH)D levels. Therefore, to address the inconsistencies, we conducted a systematic review and dose-response meta-analysis to accurately determine the effect of omega-3 supplementation on 25(OH)D levels in humans.

Methods: We performed a comprehensive literature search in Web of Science, PubMed/Medline, Scopus, and Embase databases from inception up to January 2020. We included only randomized controlled trials (RCTs). We used weighted mean difference (WMD) with 95% confidence interval (CI) to assess the influence of omega-3 supplementation on serum 25(OH)D levels using the random-effects model.

Results: Our pooled results of 10 RCTs demonstrated an overall significant increase in 25(OH)D levels following omega-3 intake (WMD = 3.77 ng/ml, 95% CI: 1.29, 6.25). In addition, 25(OH)D levels were significantly increased when the intervention duration lasted >8 weeks and when the baseline serum 25(OH)D level was ˂20 ng/ml. Moreover, omega-3 intake ≤1000 mg/day resulted in higher 25(OH)D levels compared to omega-3 intake >1000 mg/day.

Conclusion: In conclusion, omega-3 supplementation increased 25(OH)D concentrations, particularly with dosages ≤1000 mg/day and intervention durations >8 weeks.
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http://dx.doi.org/10.1080/10408398.2020.1863905DOI Listing
December 2020

Impact of orange juice consumption on cardiovascular disease risk factors: a systematic review and meta-analysis of randomized-controlled trials.

Crit Rev Food Sci Nutr 2020 Dec 22:1-14. Epub 2020 Dec 22.

Department of Pharmacology, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

Cardiovascular disease (CVD) is the greatest cause of premature death and disability globally. Numerous therapeutic strategies have been developed to improve and prevent the adverse cardiovascular events, including nutritional approaches. This systematic review and meta-analysis summarized the evidence on orange juice consumption on CVD risk factors. Four databases were searched up to September 2020. Ten randomized controlled trials were included in the final analysis. Pooled results demonstrated a significant effect of orange juice on glucose (WMD: -2.92 mg/dl, 95% CI: -5.327, -0.530, p = 0.017), insulin (WMD: -1.229 μU/ml, 95% CI: -2.083, -0.374, p = 0.005), HOMA-IR (WMD: -0.464, 95% CI: -0.747, -0.181, p = 0.001), total cholesterol (WMD: -9.84 mg/dl, 95% CI: -15.43, -4.24, p = 0.001), LDL-C (WMD: -9.14 mg/dl, 95% CI: -15.79, -2.49, p = 0.007), and CRP (WMD: -0.467 mg/l, 95% CI: -0.815, -0.120, p = 0.008) compared to control group. However, the effect of orange juice on body composition factors and other CVD risk factors was not significant compared to control group. These lowering effects of glucose, HOMA-IR, total cholesterol, and LDL-C were robust in subgroups with orange juice consumption ≥500 ml/day. This meta-analysis suggests that orange juice may be beneficial in improving several CVD risk factors.
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http://dx.doi.org/10.1080/10408398.2020.1865263DOI Listing
December 2020

Preoperative cervical cytology as a prognostic factor in endometrioid-type endometrial cancer: A single-center experience from Saudi Arabia.

Avicenna J Med 2020 Jul-Sep;10(3):111-117. Epub 2020 Jul 3.

College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

Objectives: The objectives of this study were (1) to estimate the frequency of preoperative abnormal cervical cytology (CC), (2) to explore correlations between preoperative CC and specific clinicopathological prognostic factors (tumor stage, endometrioid grade, myometrial invasion, lymphovascular space involvement, cervical involvement, and recurrence), and (3) to examine the impact of preoperative CC on disease-free survival (DFS) and overall survival (OS) in Saudi patients with endometrioid-type endometrial cancer (EC).

Materials And Methods: A retrospective cross-sectional study was conducted at a tertiary hospital in Saudi Arabia. The study's inclusion criteria included: (1) patients who underwent staging operation for EC from 2010-2014, (2) patients who had preoperative CC results within 3 months before staging operation, and (3) patients with final histopathological diagnosis of endometrioid-type EC.

Results: Hundred and sixteen patients ( = 116) met the study's inclusion criteria. CC results were abnormal in 46 patients (39.7%). Patients with abnormal CC had statistically significant higher rates of unfavorable Grades II-III tumor and cervical involvement than patients with normal CC ( = 0.004, chi-square test). There were no statistically significant differences (log-rank test) between patients with normal and abnormal CC with regard to DFS ( = 0.525) and OS ( = 0.166). Multivariate analyses of DFS and OS (Cox proportional hazards model) failed to show preoperative CC as a significant independent prognostic factor of DFS and OS ( > 0.05).

Conclusion: The frequency of abnormal preoperative CC in patients with endometrioid-type EC is not uncommon. Abnormal CC correlates with poor prognostic factors, namely high tumor grade and cervical involvement. Preoperative CC is not a significant independent prognostic factor of survival.
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http://dx.doi.org/10.4103/ajm.ajm_147_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414599PMC
July 2020

Preoperative Leukocytosis as a Prognostic Marker in Endometrioid-Type Endometrial Cancer: A Single-Center Experience from Saudi Arabia.

Gulf J Oncolog 2020 Jan;1(32):51-58

College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

Introduction: Only a few studies (n=5) have focused on the importance of preoperative high white blood cell (WBC) count (leukocytosis) as a prognostic marker in patients with endometrial cancer (EC). Nevertheless, more related studies are needed to solidly corroborate these findings. To the best of our knowledge, no such study has been conducted in the Gulf region and Saudi Arabia in particular.

Methods: A retrospective cross-sectional study was conducted at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. The medical records of 130 patients with endometrioid-type EC were reviewed for clinico-pathological factors (that is, age, tumor stage, endometrioid grade, myometrial invasion depth, lymphovascular space involvement and recurrence) and survival outcomes. Survival outcomes included disease-free survival (DFS) and overall survival (OS). Leukocytosis was defined as a WBC count level >10 x 103 cells/uL. Chisquare test was used for univariate analysis of categorical data. Survival analyses of DFS and OS were calculated according to the Kaplan-Meier estimates method and compared by using two-tailed log-rank test. Univariate and multivariate analyses of survival were performed using Cox proportional hazards model. Statistical significance was regarded as a p value <0.05.

Results: The mean age was 59 ± 10.5 years (range: 36-99). The overall mean preoperative WBC count was 7.7 ± 2.4 x 103 cells/uL (range: 2.7-17 x 103). The frequency of preoperative leukocytosis was 18.5% (n=24). Patients with preoperative leukocytosis have statistically significant higher rates of advanced FIGO stage III-IV disease (p=0.007) and positive tumor recurrence (p=0.009) than patients with normal preoperative WBC count (chisquare test). Patients with preoperative leukocytosis have a higher statistically significant probability of developing recurrence than patients with preoperative normal WBC count (29.4 vs. 11.8%, p=0.008, log-rank test). Patients with preoperative leukocytosis have statistically significant lower mean DFS (58.3 ± 6.9 vs. 67.9 ± 2.3 months, p=0.015) and 5-year DFS rate (66.7 vs. 86.8%, p=0.015) than patients with normal preoperative WBC counts (log-rank test). However, there were no statistically significant differences between patients with preoperative leukocytosis and normal WBC counts in terms of mean OS (73.8 ± 4.5 vs. 79.3 ± 2.1, p=0.581) and 5-year OS rate (87.5 vs. 91.5%, p=0.581), respectively (log-rank test). Multivariate analyses using Cox proportional hazards model failed to significantly demonstrate preoperative WBC count as an independent prognostic factor of DFS and OS (log-rank test, p>0.05).

Conclusion: Preoperative leukocytosis is not rare in patients with endometrioid-type EC. Besides, preoperative leukocytosis is correlated with poor tumor FIGO stage, higher cumulative incidence of relapse and poor DFS in the univariate analysis. Our study suggests that preoperative leukocytosis may identify high-risk patients who may require more intensified therapy in terms of aggressive debulking and/or perioperative chemotherapy.
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January 2020

Genetic heterogeneity and evolutionary history of high-grade ovarian carcinoma and matched distant metastases.

Br J Cancer 2020 04 26;122(8):1219-1230. Epub 2020 Feb 26.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Background: High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian carcinoma, associated with poor clinical outcome and metastatic disease. Although metastatic processes are becoming more understandable, the genomic landscape and metastatic progression in HGSOC has not been elucidated.

Methods: Multi-region whole-exome sequencing was performed on HGSOC primary tumours and their metastases (n = 33 tumour regions) from six patients. The resulting somatic variants were analysed to delineate tumour evolution and metastatic dissemination, and to compare the repertoire of events between primary HGSOC and metastasis.

Results: All cases presented branching evolution patterns in primary HGSOC, with three cases further showing parallel evolution in which different mutations on separate branches of a phylogenetic tree converge on the same gene. Furthermore, linear metastatic progression was observed in 67% of cases with late dissemination, in which the metastatic tumour mostly acquires the same mutational process active in primary tumour, and parallel metastatic progression, with early dissemination in the remaining 33.3% of cases. Metastatic-specific SNVs were further confirmed as late dissemination events. We also found the involvement of metastatic-specific driver events in the Wnt/β-catenin pathway, and identified potential clinically actionable events in individual patients of the metastatic HGSOC cohort.

Conclusions: This study provides deeper insights into clonal evolution and mutational processes that can pave the way to new therapeutic targets.
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http://dx.doi.org/10.1038/s41416-020-0763-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156387PMC
April 2020

Telomerase reverse transcriptase promoter mutations in cancers derived from multiple organ sites among middle eastern population.

Genomics 2020 03 31;112(2):1746-1753. Epub 2019 Oct 31.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia. Electronic address:

Sanger Sequencing and immunohistochemistry was employed to investigate the TERT promoter mutations and TERT protein expression with their association to clinicopathological characteristics in over 2200 samples of Middle Eastern origin from 13 different types of cancers. The TERT promoter mutations were most frequently present in bladder cancer (68.6%), followed by central nervous system tumors (28.7%), thyroid cancer (15.4%), prostate cancer (9.3%), endometrial carcinoma (3.7%), rhabdomyosarcoma (1.4%), colorectal cancer (1%), epithelial ovarian carcinoma (0.7%) and breast cancer (0.7%). No mutations were observed in other types of cancers. In bladder cancer, we found significant inverse association with metastasis and a trend to good survival in patients with TERT mutations. In gliomas, TERT promoter mutations predicted poor prognosis. In thyroid cancer, high frequency of TERT mutation was observed in poorly differentiated carcinoma. In addition, TERT promoter mutations were associated with aggressive markers and poor outcome in follicular thyroid carcinomas.
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http://dx.doi.org/10.1016/j.ygeno.2019.09.017DOI Listing
March 2020

Prevalence, spectrum, and founder effect of BRCA1 and BRCA2 mutations in epithelial ovarian cancer from the Middle East.

Hum Mutat 2019 06 18;40(6):729-733. Epub 2019 Mar 18.

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Germline mutations in breast cancer susceptibility gene 1 and 2 have previously been estimated to contribute to 13-18% of all epithelial ovarian cancer (EOC). To characterize the prevalence and effect of BRCA1 and BRCA2 mutations in Middle Eastern EOC patients, BRCA mutation screening was performed in 407 unselected ovarian cancer patients using targeted capture and/or Sanger sequencing. A total of 19 different pathogenic variants (PVs) were identified in 50 (12.3%) women. Nine PVs were recurrent accounting for 80% of cases with PVs (40/50) in the entire cohort. Founder mutation analysis revealed only two mutations (c.4136_4137delCT and c.1140dupG) sharing the same haplotypes thus representing founder mutations in the Middle Eastern population. Identification of the mutation spectrum, prevalence, and founder effect in Middle Eastern population facilitates genetic counseling, risk assessment, and development of a cost-effective screening strategy.
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http://dx.doi.org/10.1002/humu.23736DOI Listing
June 2019

Preoperative Anemia as a Prognostic Factor in Endometrioid-Type Endometrial Carcinoma.

J Obstet Gynaecol Can 2018 11;40(11):1393-1400

Department of Surgery, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Department of Obstetrics and Gynecology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. Electronic address:

Objective: This study sought to determine the frequency of preoperative anemia (hemoglobin level <12 g/dL) and its prognostic significance for clinicopathological factors and survival outcomes in Saudi patients with endometrioid-type endometrial carcinoma (EC).

Methods: A retrospective cross-sectional study was conducted at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. A total of 148 patients who underwent staging surgery for primary EC were retrospectively analyzed for perioperative details regarding clinicopathological factors and survival.

Results: The frequency of preoperative anemia was 27.7% (n = 41). Patients with advanced FIGO disease (stages III-IV), unfavourable endometrioid tumour grade II-III, ≥50% myometrial invasion, positive lymphovascular space invasion, and tumour recurrence had statistically significant lower mean preoperative hemoglobin levels (two-tailed Mann-Whitney U test; P < 0.05). Patients with preoperative anemia had statistically significant higher rates of advanced FIGO stage III-IV (P = 0.0000), unfavourable grades II-III endometrioid histology (P = 0.0005), ≥50% myometrial invasion (P = 0.0016), positive lymphovascular space invasion (P = 0.0019), and tumour recurrence (P = 0.0064) than patients without preoperative anemia (two-tailed chi-square test). In a univariate analysis, patients with preoperative anemia had statistically lower significant mean 5-year disease-free survival (DFS) and overall survival (OS) rates than patients without preoperative anemia (log-rank test; P < 0.0001 and P < 0.0003, respectively). In a multivariate analysis, preoperative anemia was shown to be an independent prognostic factor for 5-year DFS (P = 0.0303), but not OS (P = 0.2588).

Conclusion: In patients with endometrioid-type EC, the preoperative anemia is fairly common. Moreover, preoperative anemia is correlated with a number of unfavourable clinicopathological factors, as well as poor survival (in terms of DFS and OS) in the univariate analysis.
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http://dx.doi.org/10.1016/j.jogc.2018.05.005DOI Listing
November 2018

ABO Blood Group and Endometrial Carcinoma: A Preliminary Single-Center Experience from Saudi Arabia.

Cureus 2017 Dec 18;9(12):e1959. Epub 2017 Dec 18.

Obstetrics & Gynecology, King Faisal Specialist Hospital and Research Center Riyadh, Saudi Arabia.

Introduction: Inherited ABO blood groups have been shown to play possible contributions in the pathogenesis of various gynecologic and non-gynecologic carcinomas. With regard to gynecologic carcinomas, there is a confined number of studies that explored the relationship between ABO blood group and endometrial carcinoma (EC) in the PubMed-indexed literature. To the best of our knowledge, no such study has ever been conducted in Saudi Arabia.

Objectives: Our study has two objectives: (I) to determine the prevalence of ABO blood groups among Saudi patients with EC, and (II) to explore the relationship between ABO blood group and several clinico-pathological prognostic parameters (namely: menopausal status [age], body mass index [BMI], tumor grade, FIGO [Fédération Internationale de Gynécologie et d'Obstétrique] stage and recurrence) in Saudi patients with EC.

Materials And Methods: A retrospective cross-sectional study from 01-January-2010 to 31-July-2014 was conducted at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia - a referral tertiary healthcare institute. One-hundred and fourteen patients (n=114) were included in the study. Clinico-pathological data were extrapolated from medical records, and their association with ABO blood groups were evaluated. Categorical data were presented as number of cases (n) and percentages (%). Two-tailed Chi-square test was used for univariate analysis. For all purposes, p values <0.05 were regarded as statistically significant.

Results: The mean age and BMI were 59.5 ± 10.8 years (range: 31 - 90) and 36.6 ± 8.6 kg/m (range: 17 - 60), respectively. The vast majority of patients were post-menopausal (86%), had BMI >28 kg/m (84.2%), diagnosed with early FIGO stage I-II (76.3%) and developed no recurrence (86.8%). The frequencies of ABO blood group types A, B, AB, and O were 28.1%, 12.3%, 3.5% and 56.1%, respectively. When ABO blood groups were analyzed as four different types (A, B, AB and O), O-type was the most common ABO blood group in pre- and post-menopausal EC patients (43.8% and 58.2%, respectively; p=0.14). There were no statistically significant correlations between ABO blood groups and all the examined clinico-pathological factors. Moreover, when ABO blood groups were analyzed as two different types (O and non-O), similar results were obtained; no statistically significant correlations were found between ABO blood groups and all the examined clinico-pathological factors.

Conclusions:  O-type was the most prevalent ABO blood group among Saudi Arabian patients with EC, and our finding was different from the existing literature, probably highlighting an ethnic-related variance. Furthermore, no statistically significant correlations were identified between ABO blood groups and all the examined clinico-pathological factors. Also, routine ABO blood group may emerge as a clinically accessible, beneficial and economical biomarker for a possible EC vulnerability. A large-sized case-control study is needed to withdraw solid conclusions.
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http://dx.doi.org/10.7759/cureus.1959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815653PMC
December 2017

FoxM1 and β-catenin predicts aggressiveness in Middle Eastern ovarian cancer and their co-targeting impairs the growth of ovarian cancer cells.

Oncotarget 2018 Jan 16;9(3):3590-3604. Epub 2017 Dec 16.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Epithelial ovarian cancer (EOC) is a highly lethal disease with poor prognosis especially in advanced stage tumor. Emerging evidence has reported that aberrant upregulation of FoxM1 and β-catenin are closely associated with aggressiveness of human cancer. However, interplay between these factors in the aggressiveness of EOC is not fully illustrated. In this study, we show that FoxM1 is frequently increased in Middle Eastern EOC and associated with high proliferative index ( = 0.0007) and high grade tumor ( = 0.0024). Interestingly, FoxM1 is significantly associated with elevated nuclear β-catenin and the concomitant increase of FoxM1 and β-catenin is associated with advanced stage of EOC by immunohistochemical analysis of 261 samples of Saudi patients with EOC. Functional analysis showed that β-catenin is a direct transcriptional target of FoxM1 in EOC cell lines. FoxM1 inhibition either by specific inhibitor, thiostrepton or siRNA suppressed β-catenin expression, whereas overexpression of FoxM1 increased nuclear β-catenin expression. We identified two FoxM1 binding sites in the β-catenin promoter that specifically bound to FoxM1 protein. Down-regulation of FoxM1 using thiostrepton induced apoptosis and inhibited cell migration/invasion in EOC cells. Moreover, co-inhibition of FoxM1 by thiostrepton and β-catenin by FH535 significantly and synergistically inhibited EOC cell growth and . Collectively, our findings confer that co-targeting FoxM1/β-catenin signaling cascade may be a promising molecular therapeutic choice in advanced EOC.
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http://dx.doi.org/10.18632/oncotarget.23338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790485PMC
January 2018

Preoperative elevated platelet count and thrombocytosis in gynecologic malignancies.

Arch Gynecol Obstet 2018 04 5;297(4):1071-1072. Epub 2018 Feb 5.

College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1007/s00404-018-4706-8DOI Listing
April 2018

Preoperative thrombocytosis as a prognostic factor in endometrioid-type endometrial carcinoma.

Ann Saudi Med 2017 Sep-Oct;37(5):393-400

Correspondence: Dr. Ismail A. Al-Badawi Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Centre, MBC 52, P.O. Box 3354, Riyadh 11211, Saudi Arabia ORCID: http://orcid.org/0000- 0001-5775-9702.

Background: The impact of preoperative thrombocytosis as a prognostic factor in endometrial carcinoma (EC) remains uncertain and has never been examined in Saudi Arabia.

Objectives: To determine the prevalence of preoperative thrombocytosis (platelet count > 400 000/ μL), and its prognostic significance for clinicopathological factors and survival in Saudi patients with endometrioid-type EC.

Design: A retrospective cross-sectional study from January 2010 to December 2013.

Setting: A referral tertiary healthcare institute.

Patients And Methods: Patients who underwent staging surgery for primary endometrioid-type EC were retrospectively analyzed for perioperative details: age, preoperative platelet count, International Federation of Gynecology and Obstetrics (FIGO) stage, endometrioid grade, recurrence, disease-free survival (DFS) and overall survival (OS). Survival analysis was conducted using Kaplan-Meier estimates and a Cox proportional hazards model.

Main Outcome Measures: Prevalence of preoperative thrombocytosis, DFS and OS.

Results: In 162 patients who met inclusion criteria, the frequency of preoperative thrombocytosis was 8.6% (n=14). Patients with advanced FIGO disease (stages III-IV) and recurrence had significantly higher mean preoperative platelet counts than patients with early FIGO disease (stages I-II) and no recurrence (P=.0080 and P=.0063, respectively). Patients with thrombocytosis had statistically significant higher rates of advanced FIGO stages III-IV disease, unfavorable grades II-III endometrioid histology and recurrence than patients with preoperative platelet counts.
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http://dx.doi.org/10.5144/0256-4947.2017.393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074199PMC
May 2018

Expanding the spectrum of germline variants in cancer.

Hum Genet 2017 11 3;136(11-12):1431-1444. Epub 2017 Oct 3.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Our ability to identify germline variants in hereditary cancer cases remains challenged by the incomplete cataloging of relevant genes and lack of consensus on who should be tested. We designed a panel [hereditary oncogenesis predisposition evaluation (HOPE)] that encompasses most of the genes known to be associated with cancer development and tested its yield on more than 1300 samples of cancer patients. Pathogenic or likely pathogenic variants in high and intermediate risk genes were identified in 16, 23.9, 9.7 and 2.7%, respectively, of peripheral blood or normal tissue samples taken from patients with breast, ovarian, colorectal and thyroid cancer. To confirm specificity of these findings, we tested an ethnically matched cohort of 816 individuals and only identified pathogenic or likely pathogenic variants in 1.59% (0.98% in high risk and 0.61% in intermediate risk). Remarkably, pathogenic or likely pathogenic alleles in DNA repair/genomic instability genes (other than BRCA2, ATM and PALB2) accounted for at least 16.8, 11.1, 50 and 45.5% of mutation-positive breast, ovarian, thyroid and colorectal cancer patients, respectively. Family history was noticeably lacking in a substantial fraction of mutation-positive cases (63.7, 81.5, 42.4 and 87.5% in breast, ovarian, colorectal and thyroid, respectively). Our results show high contribution of germline mutations to cancer predisposition that extends beyond "classical" hereditary cancer genes. Family history was lacking in 63.5% mutation-positive cases, shows that hereditary cancer need not appear familial and suggests that relaxed selection of cancer patients for hereditary cancer panels should be considered.
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http://dx.doi.org/10.1007/s00439-017-1845-0DOI Listing
November 2017

Triple Synchronous Primary Neoplasms of the Cervix, Endometrium, and Ovary: A Rare Case Report and Summary of All the English PubMed-Indexed Literature.

Case Rep Obstet Gynecol 2017 23;2017:9705078. Epub 2017 Aug 23.

College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

The incidence rate of triple or more synchronous primary neoplasms of the female genital system is exceedingly uncommon. To the best of our knowledge, only 13 such cases have been reported in the PubMed-indexed English literature. Herein, we report a single case of triple synchronous primary neoplasms of the cervix, endometrium, and left ovary with three distinct histological patterns that were not reported previously. Moreover, we briefly present a summary table of all the English PubMed-indexed cases of triple or more synchronous primary neoplasms of the female genital system ( = 13).
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http://dx.doi.org/10.1155/2017/9705078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587927PMC
August 2017

Clinical Practice Guidelines on the Screening and Treatment of Precancerous Lesions for Cervical Cancer Prevention in Saudi Arabia.

Ann Saudi Med 2016 Sep-Oct;36(5):313-320

Hazem Mahmoud Al-Mandeel,, Associate Professor, King Khalid University Hospital,, Obstetrics and Gynecology,, College of Medicine and King Saud Medical University, Medical City,, King Saud University,, PO Box 7805, Riyadh 11472,, Saudi Arabia, T: +966-11-469-1775, F: +966-11-467-9557, ORCID ID: http://orcid.org/0000-0002-2329-0288.

Background: Cervical cancer is the third most common gynecological malignancy in Saudi women with an estimated incidence rate of 1.9 cases per 100 000 women-years. More than 40% of cervical cancer cases are diagnosed at advanced stages due to lack of a routine screening program in Saudi Arabia. Thus, national guidelines for routine screening and treatment of precancerous cervical lesions are needed.

Methods: The Saudi Centre for Evidence-Based Healthcare invited a panel of local experts and partnered them with a team from McMaster University in Canada for methodological support, to develop national clinical practice guidelines on the screening and treatment of precancerous lesions for cervical cancer. After the panel identified key clinical questions, the McMaster University working group updated existing systematic reviews that had been used for the 2013 WHO Guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. Recommendations were based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. Those recommendations took into account the available evidence, patient values and preferences, and resource use in the Saudi context. The panel provided recommendations on two major issues: screening for precancerous lesions (cervical intraepithelial neoplasia 2 & 3) and treatment of those lesions to prevent cervical cancer in women who tested positive after screening.

Conclusions: The Saudi expert panel recommends using the HPV DNA test followed by colposcopy or cytology (Pap test) followed by colposcopy to screen for CIN2+ in women at risk of cervical cancer. The panel recommends cryotherapy or loop excision electrosurgery procedure (LEEP) over cold knife cone biopsy to treat women at risk of cervical cancer that tests positive for CIN2+. Universal screening for precancerous cervical dysplasia in women in Saudi Arabia is recommended using HPV testing and or cytology. Either cryotherapy or LEEP are preferred for treatment.

Limitations: National studies on cervical cancer screening modalities and treatment of precancerous cervical lesions, including HPV prevalence and its association with cervical cancer, are scarce.
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http://dx.doi.org/10.5144/0256-4947.2016.313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074318PMC
February 2017

Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy for Management of Peritoneal Sarcomatosis: A Preliminary Single-Center Experience from Saudi Arabia.

Gastroenterol Res Pract 2016 24;2016:6567473. Epub 2016 Apr 24.

College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.

Aim. To report our preliminary single-center experience with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for management of peritoneal sarcomatosis (PS). Methods. Eleven patients were retrospectively analyzed for perioperative details. Results. Cytoreduction completeness (CC-0/1) was achieved in all patients with median peritoneal cancer index (PCI) of 14 ± 8.9 (range: 3-29). Combination cisplatin + doxorubicin HIPEC chemotherapy was used in 6 patients. Five patients received intraoperative radiation therapy (IORT). The median operative time, estimated blood loss, and hospital stay were 8 ± 1.4 hours (range: 6-10), 1000 ± 250 mL (range: 700-3850), and 11 ± 2.4 days (range: 7-15), respectively. Major postoperative Clavien-Dindo grade III/IV complications occurred in 1 patient and none developed HIPEC chemotherapy-related toxicities. The median overall survival (OS) and disease-free survival (DFS) after CRS + HIPEC were 28.3 ± 3.2 and 18.0 ± 4.0 months, respectively. The median follow-up time was 12 months (range: 6-33). Univariate analysis of several prognostic factors (age, gender, PS presentation/pathology, CC, PCI, HIPEC chemotherapy, and IORT) did not demonstrate statistically significant differences of OS and DFS. Conclusion. CRS + HIPEC appear to be feasible, safe, and offer survival oncological benefits. However, definitive conclusions cannot be deduced.
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http://dx.doi.org/10.1155/2016/6567473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860243PMC
May 2016

Single-port laparoscopic surgery for benign salpingo-ovarian pathology: a single-center experience from Saudi Arabia.

Ann Saudi Med 2016 Jan-Feb;36(1):64-9. Epub 2016 Jan 26.

Dr. ismail A. Al-Badawi, Department of Obstetrics and Gynecology,, King Faisal Specialist Hospital and Research Centre,, PO Box 3354 Riyadh 11211, Saudi Arabia, T: +966-011-442-7392, F: +966-011-442-7393,

Background: There are limited data and few solid conclusions on the use of single-port laparoscopic surgery (SPLS) in gynecologic procedures.

Objective: The objective of our descriptive study was to review our single-center experience with benign salpingo-ovarian conditions (feasibility, safety and surgical outcomes).

Design: A retrospective cross-sectional study from January-2012 to October-2014.

Setting: King Faisal Specialist Hospital & Research Center--a referral tertiary healthcare center.

Patients And Methods: All gynecologic patients who underwent SPLS procedures for benign adnexal pathologies were analyzed for pre-, intra-and postoperative details. SPLS was done using a single multi-port trocar and standard laparoscopic instruments.

Main Outcome Measures: Perioperative complications and conversion rate.

Results: Eighty (n=80) patients underwent SPLS interventions. the median age and BMi were 37 years and 24.6 kg/m2, respectively. Thirty-one patients (38.8%) had >=1 previous abdominopelvic surgeries. Of 104 SPLS procedures conducted, the three most common procedures were unilateral ovarian cystectomy (n=21/104; 20.2%), bilateral ovarian transposition (n=20/104; 19.2%), and unilateral salpingo-oophorectomy (n=16/104; 15.4%). No patient required addition of extra ports or conversion to conventional multi-port laparoscopy or laparotomy. The median operative time, estimated blood loss and hospital stay were 66 min, 10 mL and 1 day, respectively. No patient experienced major intraoperative or postoperative complications. the median postoperative pain grade using the visual analogue scale was 2 (examined in 74 of 80 patients). At six-weeks postoperatively, the median wound scar length (measured at outpatient clinic) was 1.2 cm.

Conclusion: SPLS in the management of benign salpingo-ovarian conditions is generally feasible, potentially safe, and associated with satisfactory operative and postoperative outcomes.

Limitations: Retrospective and non-comparative design. Single-center experience. Subjective scores of the patients' self-reported satisfaction about post-operative pain, subject to recall bias.
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http://dx.doi.org/10.5144/0256-4947.2016.26.1.1200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074270PMC
December 2016

Extrauterine epithelioid trophoblastic tumor arising in the ovary with multiple metastases: a case report.

Int J Surg Pathol 2015 Jun 18;23(4):339-44. Epub 2015 Feb 18.

Department of Obstetrics and Gynaecology, King Faisal Specialist Hospital and Research Center, Saudi Arabia.

Epithelioid trophoblastic tumor is a neoplasm of the chorionic-type intermediate trophoblasts. It is considered a rare gestational trophoblastic disease and is frequently misdiagnosed as carcinoma. Extrauterine epithelioid trophoblastic tumor has been reported in multiple anatomical sites. We report a case of a 50-year-old woman who presented with abdominal pain and distension. Her initial β-human chorionic gonatotropin level was 806.7 IU/L. Imaging showed a large complex ovarian mass with peritoneal and subcapsular hepatic deposits as well as pulmonary nodules. Morphological features of the tumor and its immunohistochemical reactivity to CK8/18, CK7, p63, and CD10 were consistent with the diagnosis of an extrauterine epithelioid trophoblastic tumor arising from the ovary. The differential diagnoses, including other ovarian tumors, were ruled out on the basis of morphology and negative immunostaining to a relatively extended panel of antibodies. A prolonged follow up of these cases and the recognition of such rare tumors in unusual sites are crucial to the diagnosing pathologist and treating physician.
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http://dx.doi.org/10.1177/1066896915570661DOI Listing
June 2015

Vulvar extrauterine endometrial stromal sarcoma: A case report and literature review.

Hematol Oncol Stem Cell Ther 2015 Sep 6;8(3):125-9. Epub 2015 Jan 6.

Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Centre (KFSH & RC), P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address:

Endometrial stromal sarcoma (ESS) is an extremely rare neoplasm accounting for only 0.2% of all uterine malignancies and for 15-26% of primary uterine sarcomas. The annual incidence of ESS is 1-2 per million women. Herein, to the best of our knowledge, we present the first reported case of ESS of the vulva in a 50-year-old female presenting with per vaginal spotting over a period of three months. Her past surgical history included a subtotal hysterectomy and left salpingo-oophorectomy for uterine fibroids ten years previously. On examination, a 3.5×3×2 cm cystic mass was found in the right labia majora. The mass was excised and the diagnosis of endometrial stromal sarcoma was made. Subsequent metastatic workup was negative and the patient was started on megestrol acetate. She has remained disease free with no signs or symptoms of recurrent or advanced disease for 28 months.
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http://dx.doi.org/10.1016/j.hemonc.2014.12.003DOI Listing
September 2015

Unilateral ectopic mammary-like tissue in the vulva.

J Obstet Gynaecol Can 2014 Nov;36(11):951

King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1016/S1701-2163(15)30403-5DOI Listing
November 2014

Human papillomavirus prevalence and type distribution among women attending routine gynecological examinations in Saudi Arabia.

BMC Infect Dis 2014 Dec 14;14:643. Epub 2014 Dec 14.

GlaxoSmithKline Vaccines, Wavre, Belgium.

Background: Cervical cancer (CC) is caused by persistent infection with high-risk (HR) human papillomavirus (HPV) types. In Saudi Arabia which has a population of 6.5 million women over the age of 15 years, approximately 152 new cases of CC are diagnosed and 55 women die from the disease annually. Nevertheless current epidemiological data for HPV in this population are limited. This study evaluated the prevalence and type distribution of HPV and documented the awareness of HPV infection and health-related behavior among Saudi and non-Saudi women attending routine examination.

Methods: This was an observational, epidemiological cross-sectional study conducted between April 2010 and December 2011 at three hospitals in Saudi Arabia. Cervical samples from women aged ≥15 years, who were attending routine gynecological examinations were collected and tested for HPV-DNA by polymerase chain reaction and typed using the SPF10 DEIA/LiPA25 system. Two questionnaires on health-related behavior and awareness of HPV infection were completed.

Results: A total of 417 women, mean age (standard deviation) 41.9 (±10.4) years, were included in the final analysis, of whom 77% (321/417) were Saudi nationals. HPV-DNA was detected in 9.8% women (41/417, 95% confidence interval [CI]: 7.1-13.1). The prevalence of any HR-HPV by age was: 25-34 years: 3.0%; 35-44 years: 4.5%; 45-54 years: 3.2%; >55 years: 10.9%. The most prevalent HR-HPV-types were: HPV-68/73 (5 cases); HPV-18 (4 cases); HPV-16 (3 cases). The most prevalent low risk (LR) types were HPV-6 (4 cases); HPV-42, HPV-53 and HPV-54 (2 cases each). The prevalence of HPV was higher among non-Saudi nationals vs. Saudi nationals (16.7% vs. 7.8%, P = 0.0234). No statistically significant risk factors were identified: 32.2% (101/314) women were aware of HPV and 89.9% (285/317) showed an interest in HPV vaccination.

Conclusion: The overall prevalence of HPV was 9.8% in Saudi Arabia, but was higher in women over 55 years, as well as in non-Saudi nationals. These data provide a reference for public health authorities and may also help in determining future policies for the prevention of CC.

Clinical Trial Registration: NCT01213459.
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http://dx.doi.org/10.1186/s12879-014-0643-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272558PMC
December 2014

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for management of recurrent/relapsed ovarian granulosa cell tumor: a single-center experience.

J Obstet Gynaecol Res 2014 Sep;40(9):2066-75

Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

Aim: The aim of this study was to retrospectively report our experience (efficacy/morbidity) with cytoreductive surgery+hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) for the management of recurrent/relapsed ovarian granulosa cell tumors (OGCT).

Material And Methods: From 2010 to 2013, six patients underwent CRS+HIPEC. CRS was performed with standard peritonectomy procedures and visceral resections directed towards complete elimination of tumors from the abdominopelvic cavity. HIPEC was performed with cisplatin (50 mg/m²) and doxorubicin (15 mg/m²) and allowed to circulate in the abdominopelvic cavity for 90 min at 41.0-42.2°C.

Results: Cytoreduction completeness (CC-0) was achieved in all except one patient (CC-1). Five patients had OGCT recurrences in abdomen+pelvis and one patient in abdomen only. No grade V morbidity (Clavien-Dindo classification) occurred. Two patients developed lung atelectasis, which was managed by mere chest physiotherapy (grade I). One patient developed urinary tract infection (grade II) and another patient developed pneumonia (grade II) - both of which were managed by antibiotics. One patient developed splenic bed and anterior abdominal wall collections requiring ultrasound-guided aspiration without general anesthesia (grade III). One patient developed pulmonary embolism requiring intensive care-unit management (grade IV). Four chemo-naïve patients received adjuvant chemotherapy whereas the remaining two previously chemo-exposed patients received no adjuvant therapy. All patients were alive and disease-free without proof of recurrence/relapse at 40, 32, 27, 24, 20 and 16 months. The average interval of follow-up after CRS+HIPEC was roughly 27 months (range: 16-40 months).

Conclusion: CRS+HIPEC appears to be an efficacious and morbidly well-tolerated therapeutic modality for recurrent/relapsed OGCT. Long-term follow-up data and further research are needed.
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http://dx.doi.org/10.1111/jog.12460DOI Listing
September 2014