The fluorescence imaging for laparoscopic and laparotomic endometrial sentinel lymph node biopsy (FILLES) trial: Siriraj gynecologic sentinel node of endometrial cancer (SiGN-En) study.

BACKGROUND AND OBJECTIVES: The objective of this study is to establish the detection rate of sentinel lymph node (SLN) biopsies and to determine the sensitivity and false-negative rate of SLN biopsies compared with those of systematic pelvic and para-aortic lymphadenectomies in endometrial cancer. METHODS: This prospective cohort study enrolled patients with endometrial cancer who were scheduled for surgical staging. Patients with a history of chemotherapy or radiotherapy, an abnormal liver function test, or an allergy to indocyanine green (ICG) were excluded. All patients underwent surgical staging with an ICG injection at the cervix. SLNs were identified by a near-infrared fluorescent camera. All SLNs were sent to a pathologist for ultrastaging. RESULTS: From November 2019 to June 2023, 142 patients underwent SLN mapping and surgical staging. SLNs were not detected bilaterally in 8 patients. The detection rate of the SLN biopsies in this study was 91.2%. Thus, the accuracy of the SLN biopsies was 97.6%. The sensitivity for finding metastatic SLNs was 84.2%, with a negative predictive value of 97.22%. CONCLUSIONS: A SLN biopsy in endometrial cancer has a high detection rate and high accuracy. However, surgical expertise and a learning curve are required.

Treatment outcomes of early-stage endometrial cancer patients: A propensity score matching of vaginal brachytherapy versus pelvic radiotherapy.

OBJECTIVES: This study aimed to report the treatment outcomes of radiation therapy for early-stage endometrial cancer patients. In addition, this study intended to identify high-risk factors that require pelvic radiotherapy (PRT) in addition to vaginal brachytherapy (VBT) for intermediate-risk endometrial cancer patients. METHODS: Patients with early-stage endometrial cancer receiving postoperative VBT alone or with PRT were included. Propensity score matching was used to balance the two study groups. The primary endpoint was locoregional recurrence (LRR). Age-adjusted Charlson comorbidity index and substantial lymphovascular space invasion were selected for subgroup analyses to identify the benefits of PRT over VBT alone. RESULTS: From 2005 to 2017, a total of 288 patients underwent analysis following propensity score matching. Of these, 144 received VBT and 144 received PRT. There was no significant difference in 5-year LRR between VBT and PRT for both intermediate (0% vs. 0%) and high-intermediate risk patients (3.5% VBT vs. 5.4% PRT; HR 0.54: 0.05-6.00; p = 0.616). The subgroup analyses revealed no significant factors favoring PRT over VBT. Patients with high comorbidities may have higher risks of non-cancer death after receiving PRT. CONCLUSIONS: Postoperative VBT alone is sufficient for early-stage intermediate-risk endometrial cancer patients.

Prospective comparative trial comparing O-RADS, IOTA ADNEX model, and RMI score for preoperative evaluation of adnexal masses for prediction of ovarian cancer.

INTRODUCTION: Preoperative assessment of ovarian tumors to distinguish between benign and malignant is important. At this time, many diagnostic models were available and the popularity of the risk of malignancy index (RMI) in Thailand is still high. The IOTA Assessment of Different NEoplasias in adneXa (ADNEX) model and the Ovarian-Adnexal Reporting and Data System (O-RADS) model were both new models with good performance. OBJECTIVES: The purpose of this study was to compare O-RADS, RMI, and ADNEX models. DESIGN: This diagnostic study was performed using data from the prospective study. METHODS: Data from 357 patients from a previous study were included and calculated using the RMI-2 formula then applied to the O-RADS system and the IOTA ADNEX model. The diagnostic significance of the results was evaluated by receiver operating characteristic (ROC) analysis and pairwise comparison between models was made. RESULTS: The area under the receiver operating characteristic curve (AUC) to distinguish an adnexal mass as a benign or malignant tumor was 0.975 (95% CI, 0.953-0.988) for the IOTA ADNEX model; 0.974 (95% CI, 0.960-0.988) for O-RADS; 0.909 for RMI-2 (95% CI, 0.865-0.952). There were no differences in pairwise AUC comparisons between the IOTA ADNEX and O-RADS models, and both were better than those of RMI-2. CONCLUSIONS: The IOTA ADEX and O-RADS models are excellent tools for distinguishing the adnexal mass in the preoperative assessment and were better than RMI-2. The use of one of these models is recommended.

Prevalence of ovarian mass and diagnostic performance of ultrasonography pattern recognition among women at the Gynaecologic Ultrasonography Unit at University Hospital in Thailand.

The aim of this retrospective study was to determine the prevalence of ovarian masses and calculate the diagnostic performance of the pattern recognition approach in ovarian pathology. A total of 1001 patients diagnosed with ovarian mass were included, of which 92.6% were diagnosed with ovarian pathology and the presence of a pathological result, while 7.4% of cases were diagnosed with functional ovarian cyst. The prevalence of ovarian malignancy was 15%. A specific ultrasound diagnosis was suggested in 62.9% of all cases, while sonographers did not explicitly provide a diagnosis in remaining cases. A subjective assessment showed 80.3% sensitivity (95% confidence interval (CI) 68.7-89.1) and 97.6% specificity (95% CI 96-98.6) in differentiating between benign and malignant ovarian masses. The sensitivity and specificity for the diagnosis of endometriotic cyst were 77.03% and 90.63% and 63.19% and 94.3% for mature cystic teratoma, respectively. In conclusion, assessment showed good performance in differentiating between benign and malignant ovarian mass and it was possible to diagnose several specific ovarian tumours. Impact StatementWhat is already known on this subject? Pattern recognition is an acceptable method for classifying ovarian mass, which exhibits specific morphological features on grey-scale ultrasonography, and can be used to predict nature and histological type.What do the results of this study add? Even in the hands of an expert examiner, there were a number of cases in which the diagnoses could not be specifically stated. Pattern recognition correctly classified 90.3% of ovarian masses as either benign or malignant and correctly provided specific histologic diagnoses after exclusion of unspecified diagnosis in 80.6% of all cases. The diagnostic performance of this approach was high in differentiating between benign and malignant ovarian mass and in diagnosing some specific ovarian pathologies.What are the implications of these findings for clinical practice and/or further research? A subjective assessment is simple and easy to use in clinical practice and has shown promising results in classifying benign and malignant ovarian mass. Moreover, it can also be used to make some specific diagnoses. However, specialised and experienced gynaecological ultrasound examiners are required to provide the most accurate diagnosis. Therefore, criteria to describe ultrasound features and convincing operators to make a definite diagnosis as often as possible should be encouraged. A prospective study to verify diagnostic performance of pattern recognition or comparing with other ultrasonographic diagnostic tools should be considered.

A comparison of high-risk human papillomavirus DNA detection between urine and cervical sample testing in women with abnormal Pap smears.

AIMS: To compare the clinical performance of high-risk human papillomavirus (hrHPV) DNA detection between urine and cervical samples collected from the same patient for the detection of CIN2+ lesions (high-grade squamous intraepithelial lesions or cervical cancer lesions). The secondary objectives were to evaluate agreement among hrHPV genotypes and to compare patient satisfaction between urine and cervical sample collection. METHODS: This prospective cross-sectional study enrolled 96 women with abnormal cervical cytology who attended the colposcopy clinic at Siriraj Hospital (Bangkok, Thailand) between July 2016 and January 2017. Self-collected random-voiding and first stream urine samples were collected into a universal sterile urine container and immediately mixing with preservative before the pelvic examination. Cervical tissue sampling was performed according to standard treatment guidelines. Both specimens were sent for extraction and detection of hrHPV by Anyplex II HPV high-risk testing. Study patients were surveyed to compare patient satisfaction between urine and cervical sample collection. RESULTS: Carcinogenic hrHPV positive rate was 73% in urine samples and 81% in cervical samples. The sensitivity for HPV in the detection CIN2+ was high in both the urine and cervical groups at 86.2% and 94.8%, respectively. Agreement between the urine and cervical groups for HPV 16 or 18 detection was high, with kappa values of 0.86 for subtypes 16/18. Urine specimen collection had significantly higher satisfaction and acceptability than cervical specimen collection. CONCLUSION: Urine hrHPV testing by real-time polymerase chain reaction demonstrated high sensitivity and accuracy for the detection of CIN2+ lesions, with very good agreement when compared with cervical sample testing.

Comparison of surgical and oncologic outcomes in patients with clear cell ovarian carcinoma associated with and without endometriosis.

PURPOSE: To compare clinical characteristics, surgical and oncologic outcomes of clear cell ovarian cancer among patients with cancer arising from endometriosis, cancer coexisting with endometriosis, and cancer without endometriosis. METHODS: A retrospective chart review of patients diagnosed with clear cell ovarian cancer during January 1998-March 2013 was performed. All histopathology specimens were reviewed by a gynecologic pathologist and classified into one of the three following endometriosis status groups: arising group, coexisting group, or without group. The primary outcome was disease-specific survival (DSS). The secondary outcomes were progression-free survival, surgical morbidities, response rate, recurrence rate, and cancer-specific death. RESULTS: Finally, 249 patients were included. There were 82, 96, and 71 patients in the arising, coexisting, and without groups, respectively. Regarding baseline characteristics among groups, the without group was significantly older and had more advanced diseases. There was a significant difference in progression-free survival between the arising group and the without group (p = 0.003). Five-year progression-free survival rates were 62.8% in the arising group, 50.2% in the coexisting group, and 38.3% in the without group. DSS was not significantly different among groups. Multivariate analysis revealed ovarian surface invasion (HR = 2.76) and pelvic lymphadenectomy (HR = 0.39) to be independent prognostic factors for progression-free survival, whereas no remission after primary treatment (HR = 8.03) and pelvic lymphadenectomy (HR = 0.21) were prognostic factors for DSS. Intraoperative blood loss and residual tumor were significantly higher in the without group. CONCLUSIONS: Endometriosis status was found not to significantly influence surgical and oncologic outcomes in patients with clear cell ovarian cancer.

Preoperative Evaluation of the ADNEX Model for the Prediction of the Ovarian Cancer Risk of Adnexal Masses at Siriraj Hospital.

INTRODUCTION: Distinguishing benign adnexal masses from malignant tumors plays an important role in preoperative planning and improving patients' survival rates. The International Ovarian Tumor Analysis (IOTA) group developed a model termed the Assessment of Different NEoplasias in the adneXa (ADNEX). OBJECTIVE: Our objective was to evaluate the performance of the ADNEX model in distinguishing between benign and malignant tumors at a cutoff value of 10%. METHODS: This was a prospective diagnostic study. 357 patients with an adnexal mass who were scheduled for surgery at Siriraj Hospital were included from May 1, 2018, to May 30, 2019. All patients were undergoing ultrasonography, and serum CA125 was measured. Data were calculated by the ADNEX model via an IOTA ADNEX calculator. RESULTS: Of the 357 patients, 296 had benign tumors and 61 had malignant tumors. The area under the receiver operating characteristic curve for using the ADNEX model was 0.975 (95% confidence interval, 0.953-0.988). At a 10% cutoff, the sensitivity was 98.4% and specificity was 87.2%. The best cutoff value was at 16.6% in our population. CONCLUSIONS: The performance of the ADNEX model in differentiating benign and malignant tumors was excellent.

Comparison of Siriraj liquid-based solution and standard transport media for the detection of high-risk human papillomavirus in cervical specimens.

PURPOSE: To evaluate the performance of Siriraj liquid-based solution for human papillomavirus (HPV) DNA testing compared with standard transport media. METHODS: This cross-sectional study enrolled 217 women aged 30 years or older who attended for cervical cancer screening or had abnormal cervical cytology, or were diagnosed with cervical cancer at the Department of Obstetrics-Gynecology, Siriraj Hospital from March 2015 to January 2016. We excluded patients with a history of any cervical procedures, hysterectomy, or previous treatment with pelvic irradiation or chemotherapy. Two cervical specimens were collected from each participant. The standard Cervi-Collect Specimen Collection Kit was used to preserve the first sample, and Siriraj liquid-based solution was used for the second one. All samples were sent for HPV DNA testing using the same standard high-risk HPV assay. HPV test results were recorded and statistically analyzed. RESULTS: The results showed agreement between standard transport media and Siriraj liquid-based solution for HPV DNA testing, at a kappa value of 0.935 (P < 0.001). We found no discorrelation for the detection of HPV 16, which accounts for approximately 50% of cervical cancers. The relative sensitivity of Siriraj liquid-based solution and standard transport media in patients with high-grade cervical intraepithelial neoplasia or worse (CIN2+) is 98% (50/51). The relative specificity of Siriraj liquid-based solution and standard transport media in patients with non-CIN2+ is 98.1% (102/104). CONCLUSION: Siriraj liquid-based solution showed almost perfect agreement with the standard transport media for HPV DNA testing. This solution, costing 2 to 3 times less than the commercially available standard media, may be an alternative option for HPV DNA testing.

Efficacy of a single 40-mg intravenous dose of parecoxib for postoperative pain control after elective cesarean delivery: A double-blind randomized placebo-controlled trial.

AIM: The aim of this study was to determine the efficacy of a single 40-mg intravenous (i.v.) dose of parecoxib as an adjunctive analgesia to intrathecal morphine after elective cesarean delivery (CD). METHODS: A total of 82 low-risk term pregnant women who were scheduled for elective CD during the June 2014-June 2015 study period were enrolled. Two hours after surgery, subjects were randomly assigned to receive either i.v. injection of 2 mL (40 mg) parecoxib (study group; n = 41) or 2 mL normal saline solution (control group; n = 41). Patient randomization into groups was determined by the hospital's central computer system. Outcome measurements included total postoperative supplemental meperidine consumption, recorded pain score by numeric pain rating scale at 6, 12, 18, and 24 h, postoperatively, and patient satisfaction. RESULTS: Patient characteristics and pregnancy outcomes were comparable between groups. Total postoperative meperidine consumption was not significantly different between groups (12.7 ± 18.8 mg vs 8.3 ± 16.7 mg; P > 0.05). Compared with control, the study group was significantly less likely to experience moderate to severe postoperative pain (score ≥ 4) at 6 h (0% vs 21.9%; P = 0.002). Study group patients reported higher satisfaction than control group patients (median score: 8 vs 6; P < 0.01). No patients in either group reported adverse effects from their assigned intervention. CONCLUSION: Parecoxib did not demonstrate effectiveness in reducing patient requirement for supplementary meperidine after CD. However, administration of a single 40-mg dose of i.v. parecoxib after elective CD demonstrated effectiveness in reducing pain scores, with a resulting increase in patient satisfaction.

Clinical outcomes of stage I endometrial carcinoma patients treated with surgery alone: Siriraj Hospital experiences.

OBJECTIVE: To evaluate the recurrence rates and patterns of failure in patients with stage I endometrial carcinoma after surgical staging without adjuvant therapy. METHODS: Medical records of 229 patients with stage I endometrial carcinoma, treated with surgery alone between 2002 and 2010 at Siriraj Hospital were retrospectively reviewed. The primary objective of this study was recurrence rates. The secondary objectives were patterns of failure, disease-free survival, overall survival, and prognostic factors related to outcomes. RESULTS: During median follow-up time of 53.3 months, 11 recurrences (4.8%) occurred with a median time to recurrence of 21.2 months (range, 7.7 to 77.8 months). Vaginal recurrence was the most common pattern of failure (8/11 patients, 72.7%). Other recurrences were pelvic, abdominal and multiple metastases. Factors that appeared to be prognostic factors on univariate analyses were age and having high intermediate risk (HIR) (Gynecologic Oncology Group [GOG] 99 criteria), none of which showed significance in multivariate analysis. The recurrence rates were higher in the patients with HIR criteria (22.2% vs. 4.1%, p=0.013) or patients with stage IB, grade 2 endometrioid carcinoma (9.4% vs. 4.3%, p=0.199). Five-year disease-free survival and 5-year overall survival were 93.9% (95% CI, 89.9 to 5.86) and 99.5% (95% CI, 97.0 to 99.9), respectively. CONCLUSION: The patients with low risk stage I endometrial carcinoma had excellent outcomes with surgery alone. Our study showed that no single factor was demonstrated to be an independent predictor for recurrence.

Ovarian Cancer in Children and Adolescents: Treatment and Reproductive Outcomes.

OBJECTIVE: To review ovarian cancer cases in children and adolescents in Siriraj Hospital and assess the prognosis, recurrence of disease, and reproductive outcomes after treatment. MATERIALS AND METHODS: A retrospective descriptive study was conducted in ovarian cancer patients 21 years and younger who had been treated at Siriraj Hospital between January 1990 and December 2009. Medical records were reviewed and relevant data were recorded. RESULTS: A total of 48 cases met the criteria; their mean age was 16.4 years. Abdominal distension was the major symptom. 91.6% were germ cell tumors and the remaining cases were sex cord-stromal and epithelial tumors. More than half (25/48 cases) presented with stage I disease. The most common used chemotherapy regimen for germ cell tumors was BEP (bloemycin, etoposide, cisplatin). Most of patients had favorable outcomes; 46/48 cases had complete remission and retained their good health at the time of the review. We had only one recurrent case and one dead case. Ten of contacted patients had married and 3 of them had successful full-term pregnancies. CONCLUSIONS: Ovarian malignancy in children and adolescents is a rare disease. The authors reported 48 cases in 20 year-period of work. Most of them have favorable outcomes. Return of ovarian function and fertility are the topics of interest.

Incidence and clinical outcomes of non-endometrioid carcinoma of endometrium: Siriraj Hospital experience.

BACKGROUND: To study the incidence of non-endometrioid carcinoma of endometrium and compare the clinical characteristics and treatment outcomes with endometrioid carcinoma patients. MATERIALS AND METHODS: This study included 236 patients with endometrial carcinoma at Siriraj Hospital whom were diagnosed and treated from 2003 through 2006. The clinical characteristics, pathological features, treatment and clinical outcomes were collected from the medical records. The 5-year survival was calculated according to 2009 FIGO staging. RESULTS: Non-endometrioid carcinoma of endometrium accounted for 10.2% of all endometrial carcinomas (24/236 patients). The 5 -year survival rate was significantly lower in the non-endometrioid group compared to the endometrioid group (77.3% vs 96%, p<0.001) and clinical data pointed to greater malignancy. CONCLUSIONS: Non-endometrioid carcinoma of endometrium is relative rare but is more aggressive, has more distant metastasis at diagnosis with a worse survival rate than endometrioid carcinoma. Only patients in stage IA with no residual disease on a hysterectomy specimen may not need adjuvant treatment.

Agreement between colposcopic diagnosis and cervical pathology: Siriraj hospital experience.

AIM: To evaluate the agreement between colposcopic diagnosis and cervical pathology a retrospective chart review was performed. MATERIALS AND METHODS: This study included 437 patients who underwent colposcopy and cervical biopsy or conization at Siriraj Hospital from October 2010 - December 2012. The patient clinical characteristics, cervical cytology results, colposcopic diagnoses, cervical pathology results were recorded and correlations between variables were analyzed. RESULTS: Agreement of colposcopic diagnosis and cervical pathology was matched in 253 patients (57.9%). The strength of agreement with weighted Kappa statistic was 0.494 (p<0.001). Colposcopic diagnoses more often overestimated (31.1%) than underestimated (11%) the cervical pathology. Agreement of colposcopic diagnosis and cervical pathology within 1 grade was found in 411 patients (94.1%). Positive predictive value (PPV) of high grade colposcopy or more was 75.5%, whereas the negative predictive value (NPV) of insignificant and low grade colposcopy was 83.8%. False positives of high grade colposcopy or more were 21%. False negatives of insignificant or low grade colposcopy were 19.1%. CONCLUSIONS: Strength of agreement between colposcopic diagnosis and cervical pathology was found to be only moderate. A biopsy at colposcopy should be performed at a gold standard level to detect high grade lesions.

Advanced imaging applications for locally advanced cervical cancer.

Advanced imaging approaches (computed tomography, CT; magnetic resonance imaging, MRI; 18F-fluorodeoxyglucose positron emission tomography, FDG PET) have increased roles in cervical cancer staging and management. The recent FIGO (International Federation of Gynecology and Obstetrics) recommendations encouraged applications to assess the clinical extension of tumors rather than relying on clinical examinations and traditional non-cross sectional investigations. MRI appears to be better than CT for primary tumors and adjacent soft tissue involvement in the pelvis. FDG-PET/CT has increased in usage with a particular benefit for whole body evaluation of tumor metabolic activity. The potential benefits of advanced imaging are assisting selection of treatment based upon actual disease extent, to adequately treat a tumor with minimal normal tissue complications, and to predict the treatment outcomes. Furthermore, sophisticated external radiation treatment and brachytherapy absolutely require advanced imaging for target localization and radiation dose calculation.

Ruptured ovarian endodermal sinus tumor diagnosed during pregnancy: case report and review of the literature.

Pregnancy complicated by endodermal sinus tumor of the ovary is a very rare event. We present a case report of a pregnant woman with a ruptured primary endodermal sinus tumor of the ovary that was diagnosed at 13 weeks of gestation. After right salpingo-oophorectomy had been performed the patient received four cycles of combination chemotherapy (bleomycin, etoposide, and cisplatin) starting at the 15th week of pregnancy. The patient did not have any evidence of tumor recurrence for 23 months. Her baby did not have any evidence of malformations and showed normal growth and development at 21 months of follow up.

Polymorphisms in MMP9 and SIPA1 are associated with increased risk of nodal metastases in early-stage cervical cancer.

OBJECTIVE: Heritable polymorphisms modulate metastatic efficiency in Cancer Single nucleotide polymorphisms (SNPs) in MMP9 (rs17576) and SIPA1 (rs746429, rs931127) have been associated with nodal metastases in multiple cancers. We investigated the association of these SNPs with nodal metastases in early-stage cervical cancer. METHODS: Consecutive patients with stage IB cervical cancer who underwent a pelvic lymph node (LN) dissection were included. Cases (>1 positive LN, n=101) were compared with controls (negative LN pathology, n=273). Genotyping was performed on genomic DNA in the 3 SNPs using a TaqMan assay and correlated with clinical variables. RESULTS: The G allele at SIPA1 rs931127 was associated with an increased risk of nodal disease (OR 1.9, P=0.03) and approached significance at SIPA 1 rs746429 (OR 2.2, P=0.09) and MMP9 rs17576 (OR 1.5, 0.08). In patients with stage Ib1 lesions (n=304), the G allele at both SIPA1 SNPs was associated with LN metastases (rs746429 OR 10.1, P=0.01; rs931127 OR 2.4, P=0.01). In patients with no lymph vascular space invasion, SIPA1 SNPs were again associated with LN metastases, and all patients with nodal disease had at least one G allele at SIPA1 rs746429. CONCLUSIONS: In this case-control study, SNPs in SIPA1 varied statistically in cervical cancer patients with and without nodal metastases and in MMP9 after controlling for stage and lymphvascular space invasion. Further work is needed to characterize inherited polymorphisms that provide a permissive background for the metastatic cascade.

Poor survival outcome with moderate and severe hypercalcemia in gynecologic malignancy patients.

OBJECTIVE: Determine the incidence of hypercalcemia in gynecologic malignancy patients and their survival outcome. DESIGN: Single-institution retrospective clinical study. PATIENTS AND METHODS: We used Fisher exact test, Kaplan-Meier survival curves, and Cox proportional hazards model to analyze demographic and clinical data from gynecologic malignancy patients with hypercalcemia who had been treated at The University of Texas M.D. Anderson Cancer Center from September 1997 to August 2006. RESULTS: Of the 5260 gynecologic malignancy patients, 268 had hypercalcemia (5%). Of the 268, 12 were excluded because of hyperparathyroidism or coexisting malignancies; thus, 256 patients were included in the study. Most patients (82%) had mild hypercalcemia. Severity of hypercalcemia was associated with disease stage (P = 0.0019), use of hypercalcemia treatment (P < 0.0001), and survival duration (P < 0.0001). The median survival duration of patients who had not been treated for hypercalcemia was 432 days compared with 106 days in patients who had been treated. The shorter survival duration of treated patients seems to result from their disease status and hypercalcemia severity rather than whether they were treated for hypercalcemia. CONCLUSIONS: Moderate and severe hypercalcemia is associated with poorer survival duration in gynecologic malignancy patients. Early detection and treatment of hypercalcemia in these patients may prolong survival. To our knowledge, this is the first study of hypercalcemia in patients with general gynecologic malignancy.

Meigs' Syndrome with Elevated Serum CA125: Case Report and Review of the Literature.

An elevated serum CA125 level in association with a pelvic mass, pleural effusion, and massive ascites usually signifies a dismal prognosis in a postmenopausal woman. However, surgery and histopathological examination are required for the correct diagnosis and treatment, since an elevated CA125 level can be falsely positive for ovarian malignancy. We present a case of Meigs' syndrome due to right ovarian fibroma with elevated CA125 level in a postmenopausal woman.