Spectral Doppler Parameters of Fetal Main Branch Pulmonary Artery at 20 to 40 Weeks of Gestation: Reference Ranges and Percentile Calculators.

BACKGROUND: The published reference ranges for Doppler parameters of the fetal pulmonary artery (PA) are usually derived from small sample sizes with no practical standard score or percentile ranking, which hinders systematic comparisons of Doppler figures across different gestational ages (GAs). This study aimed to establish comprehensive reference ranges and provide a percentile ranking solution for key spectral Doppler parameters. METHODS: This is a cross-sectional study of 465 uncomplicated singleton pregnancies during 20 to 40 weeks of gestation. Spectral waveforms of the fetal main branch PA were obtained with a pulsed-wave Doppler interrogation site within 5 mm from the vascular origin. Fifteen spectral Doppler parameters were identified. Associations between these parameters with GA and fetal heart rate were assessed and used to develop percentile calculators via different statistical models. The root mean squared error of each model was calculated to determine the best performance solution. RESULTS: Acceptable spectral waveforms were obtained for 94.1% (438/465) of the fetuses. All Doppler parameters except pulsatility index, manually traced pulsatility index, peak systolic velocity, and time to systolic notch/acceleration time ratio were significantly correlated with GA, while acceleration time, ejection time, time to systolic notch, peak early-diastolic reversal flow, and peak early-diastolic reversal flow/peak systolic velocity ratio were additionally significantly correlated with fetal heart rate. Support vector machine models with radial basis kernel yield the best percentile estimation (root mean squared error of 2.17-4.08 and R2 of >0.98). Furthermore, the top 5% and bottom 5% outliers could be identified with positive predictive values of 0.71 to 0.97. An online user interface of percentile calculators is available at https://github.com/cmb-chula/fetoPAD. CONCLUSIONS: This study presents normal reference ranges and percentile calculators for 15 spectral Doppler parameters of the fetal main branch PA, some of which have not been published. The estimated percentiles enhance comparison and outlier detection of the spectral Doppler figures among fetuses at different GAs.

Natural Orifice Transluminal Endoscopic Surgery-assisted Vaginal Hysterectomy versus Total Laparoscopic Hysterectomy: A Single-center Retrospective Study Using Propensity Score Analysis.

OBJECTIVES: The aim of this study is to evaluate the safety and efficacy of natural orifice transluminal endoscopic surgery-assisted vaginal hysterectomy (NOTES-AVH) compared with total laparoscopic hysterectomy (TLH). MATERIALS AND METHODS: The population was a cohort of women who underwent NOTES-AVH and TLH for a nonprolapsed uterus and benign gynecological disease between October 2015 and December 2017 at Rajavithi Hospital, Thailand. Study outcomes included operative time, the requirement of blood transfusion, perioperative complications, and postoperative pain. Factors applied for propensity score matching included age, body mass index, parity, underlying disease, previous abdominal surgery, preoperative diagnosis, presence of endometriosis, and uterine weight. Mean difference (MD) and risk ratio with 95% confidence interval (CI) were calculated to represent relative measures of the comparison. RESULTS: Among the 50 pairs, there were no differences in operative time (MD 15.9 min; 95% CI - 9.3-41.1), intraoperative complications (relative risk [RR] 0.33; 95% CI 0.04-3.10) or requirement of blood transfusion (RR 1.50; 95% CI 0.26-8.60) between the NOTES-AVH and TLH groups. NOTES-AVH was associated with lower intensity of postoperative pain (MD - 1.5 at 6-h; 95% CI - 0.8-2.2 and MD - 1.0 at 24-h; 95% CI - 0.4--1.6) and shorter length of stay (MD - 0.3 day; 95% CI - 0.1-0.7 day). CONCLUSION: NOTES-AVH was safe and feasible for an alternative approach for hysterectomy. This technique was superior to TLH in that no abdominal incision was required, and postoperative pain was less intense.

Pulmonary Recruitment Maneuver for Reducing Shoulder Pain after Laparoscopic Gynecologic Surgery: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Shoulder pain is a common symptom following laparoscopic surgery. This systematic review was undertaken to assess updated evidence regarding the effectiveness and complications of the pulmonary recruitment maneuver (PRM) for reducing shoulder pain after laparoscopic gynecologic surgery. METHODS: A number of databases for randomized controlled trials (RCTs) investigating PRM for reducing shoulder pain were searched up to June 2019. Two authors independently selected potentially relevant RCTs, extracted data, assessed risk of bias, and compared results. Network meta-analyses were employed to simultaneously compare multiple interventions. Effect measures were presented as pooled mean difference (MD) or risk ratio (RR) with corresponding 95% confidence intervals (CI). RESULTS: Of the 44 records that we identified as a result of the search (excluding duplicates), eleven RCTs involving 1111 participants were included. Three studies had an unclear risk of selection bias. PRM with a maximum pressure of 40 cm H2O was most likely to result in the lowest shoulder pain intensity at 24 hours (MD -1.91; 95% CI -2.06 to -1.76) while PRM with a maximum pressure of 40 cm H2O plus intraperitoneal saline (IPS) appeared to be the most efficient at 48 hours (MD -2.09; 95% CI -2.97 to -1.21). The estimated RRs for analgesia requirement, nausea/vomiting, and cardiopulmonary events were similar across the competing interventions. CONCLUSION: PRM with 40 cm H2O performed either alone or accompanied by IPS is a promising intervention for alleviating shoulder pain within 48 hours following gynecologic laparoscopy.

Effect of Metformin For Decreasing Proliferative Marker in Women with Endometrial Cancer: A Randomized Double-blind Placebo-Controlled Trial.

OBJECTIVE: To compare the Ki-67 index of endometrial cancer cells before and after treatment between the metformin and placebo group in women with endometrial cancer (EC). METHODS: This study was a randomized, double-blind, placebo-controlled trial conducting in non-diabetic women who diagnosed with endometrioid EC and had a schedule for elective surgical staging at Rajavithi Hospital between August 2018 and June 2019. Tissue specimens were obtained via endometrial curettage at the time of initial diagnosis (pre-treatment) and hysterectomy (post-treatment) to assess the value of the Ki-67 index by immunochemistry. Patients were randomly assigned into 2 groups: metformin and placebo group. Metformin 850 mg or placebo 1 tab were administered once daily for at least 7 days, starting on the first morning after recruitment until one day before surgery. Baseline characteristics (e.g., age, body mass index, co-morbidities) including surgical and pathological characteristics were recorded. The metabolic effect of metformin was also evaluated by a recording of fasting blood sugar, HbA1C and potential adverse events including nausea, vomiting, dizziness, and hypoglycemic symptom. RESULTS: A total of 49 EC patients were included in this study. Twenty-five patients were assigned to the metformin group and 24 patients were assigned to the placebo group. Baseline demographic, surgical, and pathological characteristics between the 2 groups were similar. Metformin significantly changed the Ki-67 index relative to placebo, with a mean decrease of 23.3% (p=0.001) and a mean proportional decrease of 39.1% (p=0.006) before and after treatment. Additionally, no significant differences were detected in metabolic effects and adverse events between the metformin and the placebo groups. CONCLUSION: Short-term treatment with an oral metformin significantly reduced a proliferative marker Ki-67 index in women with endometrioid EC awaiting surgical staging. This study supports the biological effect of metformin in EC and potential applications in the adjuvant treatment in EC patients.

Progression of Precancerous Cervical Lesion Predicted by p16 Protein Immunohistochemistry in Rajavithi Hospital.

Objective: To assess the association of p16 immunohistochemical (IHC) staining in cervical squamous intraepithelial lesions (SIL) and progression of cervical intraepithelial neoplasia (CIN) 1 to CIN2+ or recurrence of CIN2+. Material and Methods: A retrospective cohort study of women with newly diagnosed SIL from colposcopy-directed biopsy at Rajavithi Hospital, 2013-2017. Pathologic specimens were reviewed and submitted to p16-IHC staining. Adjusted hazard ratios (HR) of disease-free interval (DFI) and 95% confidence intervals (CI) were carried out using the Cox proportional hazard regression model. Results: A total of 187 women was recruited, 91 cases of positive p16-IHC staining and 96 cases of negative staining. With the median follow-up time of 22 months, women with positive p16-IHC had significantly lower 1-year DFI than those with negative p16-IHC (86.8% vs. 96.6%, p = 0.006). Women with CIN 1 had 22.6% of positive p16-IHC, while those with CIN2-3 had 86.7%. From multivariate analysis, the positive p16-IHC and age > 35 years were the significant prognostic factors of progression/recurrent CIN2+ (adjusted HR 5.33, 95%CI 1.77-16.01, p = 0.003; and adjusted HR 5.80, 95%CI 1.34-25.08, p = 0.019, respectively). From subgroup analysis, the positive p16-IHC was the significant prognostic factor in women with initial CIN1 (HR 5.29, 95%CI 1.18-23.76, p = 0.030), but was not associated with prognosis in women with initial CIN 2-3 (HR 2.13, 95%CI 0.28-16.38, p = 0.468). Conclusion: Overexpression of p16 protein has the prognostic significance of SIL. Using p16-IHC may help stratify patients as low-risk and high-risk groups to progression/recurrence CIN2+.

Significance of Serum Human Epididymis Protein 4 and Cancer Antigen 125 in Distinguishing Type I and Type II Epithelial Ovarian Cancers.

OBJECTIVE: The objective of this study was to assess the effectiveness of human epididymis protein 4 (HE4) and cancer antigen 125 (CA125), and risk of ovarian malignancy algorithm (ROMA) in identifying type I and type II epithelial ovarian cancers (EOCs). METHODS: A cross-sectional diagnostic study was conducted of 499 Thai women older than 18 years who had clinically diagnosed pelvic masses and underwent elective surgery at our hospital between July 2012 and July 2014. Preoperative serum HE4 and CA125 levels were measured, and postoperative pathologic slides were reviewed. RESULTS: Of 499 Thai women enrolled in this study, 357 were noncancerous (NC), 79 had type I EOCs (EOCs-I) and 63 had type II (EOCs-II). Risk of ovarian malignancy algorithm revealed significantly better performance than HE4 and CA125 in discriminating between NC and EOCs-I (receiver operating characteristic curve and area under the curve [ROC-AUC]: ROMA, 0.86; HE4, 0.80; and CA125, 0.77), and NC and EOCs-II (ROC-AUC: ROMA, 0.97; HE4, 0.95; and CA125, 0.93). In differentiation between EOCs-I and EOCs-II (setting EOC-II as reference), ROMA yielded a better performance than HE4 and CA125 (ROC-AUC: ROMA, 0.83; HE4, 0.82; and CA125, 0.77); however, CA125 and HE4 showed higher sensitivity (CA125, 77.8%; HE4, 76.2%), whereas ROMA had the highest specificity (79.8%). CONCLUSIONS: In women who present with pelvic masses, ROMA performed very well in distinguishing between noncancer lesions and EOCs but the combined HE4 and CA125 test was more effective in predicting EOC types.

Is the Risk of Ovarian Malignancy Algorithm Better Than Other Tests for Predicting Ovarian Malignancy in Women with Pelvic Masses?

AIM: The study aimed to compare the risk of ovarian malignancy algorithm (ROMA) with risk of malignancy index (RMI), cancer antigen 125 (CA125), human epididymis protein 4 (HE4) and Sassone ultrasonography (US) score in predicting ovarian cancer (OC) in women who present with pelvic or adnexal masses. METHODS: Pelvic US, serum CA125 and HE4 levels were investigated preoperatively in consecutively enrolled Thai women over 18 years with clinically diagnosed pelvic or adnexal masses who were undergoing elective surgery at a super tertiary hospital in Thailand in 2012. ROMA, RMI and Sassone US score were calculated. RESULTS: Of 260 women who were evaluated, 74 had OC. Areas under the receiver operating characteristic curve (AUC) in predicting OC were ROMA, 86.2%; RMI, 87.6%; CA125, 80.6%; HE4, 82.4%; and Sassone score, 77.1%. ROMA and RMI performed similarly well (AUCs 84.4 and 85.6%) in premenopausal women but RMI outperformed ROMA in postmenopausal women (AUCs 87.9 and 84.0%, respectively). At the conventional cutoff value, ROMA and CA125 showed the highest sensitivity (83.8%) but HE4 had the highest specificity (86.0%). CONCLUSIONS: ROMA was comparable to RMI in predicting OC. Either ROMA or RMI can be applied to women with pelvic masses, stratified into low- and high-risk groups for OCs.

Role of Hypercoagulable State for Predictive Ovarian Malignancy in Women with a Pelvic Mass.

Background: Ovarian cancer (OC) is an important malignancy in women worldwide and is associated with hypercoagulable state and high risk of venous thromboembolism (VTE). Objective: To assess the performance of preoperative blood coagulability in discriminating between OCs and benign gynecologic diseases in women presenting with a pelvic mass, and to study the incidence of postoperative thromboembolic events. Material and Method: Preoperative coagulation tests (platelet count, prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen and D-dimer levels), and serum cancer antigen 125 (CA125) were investigated in women over 18 years old with clinically diagnosed pelvic or adnexal mass who underwent elective surgery at Rajavithi Hospital between January 2012 and December 2013. After a 9-week post-operation period, these patients were followed-up for VTE events. Results: Of 196 women, 99 had OC and 97 had benign ovarian diseases. Platelet count, fibrinogen and D-dimer levels were significantly elevated in women with OC; however, only plasma fibrinogen level was a significant predictive factor for OC. Fibrinogen and CA125 displayed similar effectiveness (areas under receiver operating characteristic curve [ROC-AUCs], 76.0% vs. 77.7%) in OC prediction. A logistic model of combined fibrinogen and CA125 showed the best performance for OC prediction (ROC-AUC, 90.1%). Postoperatively, one deep vein thrombosis event in OC patients was found, while none appeared in patients with benign gynecologic diseases. Conclusion: Women with OC are significantly more associated with hypercoagulable state than those with benign gynecologic diseases. Plasma fibrinogen level was the significant predictive factor for OC, and only 1 post-operative VTE event occurred.

Comparison of Survival Outcomes in Early Stage Invasive Adenocarcinoma with Squamous Cell Carcinoma of the Uterine Cervix.

Background: Invasive adenocarcinoma (AC) is the second most common carcinoma of the uterine cervix; however, it is not clear whether this histologic type influences survival outcomes. Objective: To evaluate the survival outcomes of patients with invasive AC compared to those with squamous cell carcinoma (SCC) in early stage cervical cancer following radical hysterectomy. Material and Method: A historical cohort study was conducted of 316 Thai women with cervical cancer clinical stage IA2-IIA (120 AC and 196 SCC) who underwent radical hysterectomy from January 1 to December 31, 2000. Results: With a median follow-up of 65.23 months, the estimated 5-year recurrence-free survival (RFS) and overall survival (OS) for patients with AC did not significantly differ from those with SCC (90.3% vs. 93.1%, p = 0.301 and 90.9% vs. 93.5%, p = 0.342 respectively). Using Cox regression analysis, cervical stroma invasion (CSI) and lymphovascular space invasion (LVSI) were the significant prognostic factors for RFS, whereas CSI was the only significant prognostic factor for OS. Women with AC who had two prognostic factors showed significantly lower 5-year RFS than those with SCC (69.5% vs. 86.3%, p = 0.035). Conclusion: Survival and recurrence were not different for surgically treated cervical cancer in women with early stage AC or SCC.

A 10-Year Clinical Experience of Gestational Trophoblastic Disease at Rajavithi Hospital, 2001-2010.

BACKGROUND: Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization and is categorized as either an hydatidiform mole (HM) or a gestational trophoblastic neoplasia (GTN). OBJECTIVE: To analyze the clinical characteristics, incidence and treatment outcomes of GTD at Rajavithi Hospital. MATERIAL AND METHOD: Medical records of women diagnosed with GTD at Rajavithi Hospital from January 1, 2001 to December 31, 2010 were retrospectively reviewed. Disease diagnosis, treatment and follow-up data were analyzed. RESULTS: A total of 329 cases of GTD were reviewed. HM was diagnosed in 167 patients (incidence 2.32 per 1,000 deliveries); 26 patients were lost to follow-up; and 49 of the remaining 141 patients (34.8%) developed post-molar GTN. In multivariable analysis, uterus >16 week size and pre-treatment human chorionic gonadotropin (hCG) level >250,000 mIU/mL were the significant risk factors for developing post-molar GTN. Of 162 patients with GTN (incidence 2.25 per 1,000 deliveries), 15 patients were lost to follow-up, and 116 patients, 29 patients and 2 patients were classified as having low-risk GTN, high-risk GTN and placental site trophoblastic disease respectively. The overall survival rate in the low-risk group was 100% whereas in the high-risk group it was 86.2%. A modified WHO prognostic score of more than five was the significant risk factor for developing resistant GTN. CONCLUSION: GTD treatment at Rajavithi Hospital showed excellent clinical outcomes. Uterus >16 weeks size and pre- treatment hCG > 250,000 mIU/mL were the significant risk factors for developing post-molar GTN in HM patients. Classifying GTN patients into low- and high-risk groups was useful in planning treatment and counseling.

Differential Diagnosis between Primary Endocervical and Endometrial Adenocarcinoma using Immunohistochemical Staining of Estrogen Receptor, Vimentin, Carcinoembryonic Antigen and p16.

BACKGROUND: When clinical and histopathological evaluation is not effective in discriminating primary endocervical adenocarcinoma (ECAs) and endometrial adenocarcinoma (EMAs), an immunohistochemistry (IHC) method is regularly used in practice, which involves staining of estrogen receptor (ER), vimentin (Vim), monoclonal carcinoembryonic antigen (mCEA) and p16. OBJECTIVE: To evaluate the performance of IHC markers, ER, Vim, mCEA and p16, in differentiating between primary ECAs and EMAs and to compare the performances of two-, three- and four-marker panels. MATERIAL AND METHOD: Women with cervical or uterine cancers who were diagnosed with mucinous or endometrioid adenocarcinoma or adenocarcinoma of non-otherwise specified, after cervical biopsy, endometrial biopsy or curettage, and who underwent elective surgery at Rajavithi Hospital between January 1, 2011 and June 30, 2012 were retrospectively reviewed. Paraffin-embedded tissue sections from pre-operative specimens were reviewed and stained with ER, Vim, mCEA and p16. Postoperative pathologic slides was reviewed and installed as the reference standard. RESULTS: Of 110 cases, 44 were primary ECAs and 66 were primary EMAs. ER and Vim were significantly expressed in EMAs (p < 0.001), while mCEA and p16 were significantly expressed in ECAs (p < 0.001). From multivariable analysis, Vim and p16 were the significant markers for differentiating ECAs and EMAs. A comparison of different combinations showed that panels of Vim/p16, ER/Vim/p16, Vim/mCEA/p16 and ER/Vim/mCEA/p16 achieved the highest overall accuracy of97.9%. CONCLUSION: Vim and p16 are the significant IHC markers and a two-marker panel of Vim/p16 is recommended for using in differentiating primary ECAs and EMAs; which a pattern of negative Vim and positive p16 expression favors diagnosis of ECAs while the converse pattern of positive Vim and negative p16 staining points to diagnosis of EMAs.

Association of Serum HE4 with Primary Tumor Diameter and Depth of Myometrial Invasion in Endometrial Cancer Patients at Rajavithi Hospital.

BACKGROUND: Although there are no biomarkers that are routinely used in endometrial cancer (EC) management, many studies have found that serum human epididymis protein 4 (HE4) is superior to cancer antigen 125 (CA125) in the detection of EC. The correlation of HE4 with two prognostic factors for EC, primary tumor diameter (PTD) and depth of myometrial invasion (DMI) may be useful in identifying EC patients at high risk of lymphatic dissemination. OBJECTIVE: To evaluate the correlation of serum HE4 with PTD and DMI in patients with EC. MATERIALS AND METHODS: A cross-sectional study was conducted on 70 EC patients who were scheduled for elective surgery at Rajavithi Hospital between 1st September 2013 and 30th May 2014. Preoperative serum levels of HE4 and CA125 were investigated, and then gross measurement of PTD was taken and postoperative pathologic slides were reviewed for DMI including histologic types, grading and staging. RESULTS: Preoperative serum HE4 levels were strongly correlated with PTD (r=0.65, p<0.001) and moderately correlated with DMI (r=0.46, p<0.001). Moreover, serum HE4 levels were significantly elevated in EC patients with PTD >2 cm (p<0.001) and DMI > 50% (p=0.004). The performance of serum HE4 in identifying EC patients at low risk and high risk of lymph node metastasis was significantly better than that of CA125 (AUC 0.88 vs. 0.65, p=0.003). At an optimal cut-off value of 70 pM/L, serum HE4 had a sensitivity of 83.3% and a specificity of 80.0%. CONCLUSIONS: In EC patients, preoperative serum HE4 is significantly correlated with PTD and DMI. Serum HE4 levels could be useful in identifying endometrial cancer patients at high risk of lymphatic spread who would benefit from systemic lymphadenectomy at the cut-off value of 70 pM/L.

Intravenous versus oral dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reaction in patients with primary ovarian, fallopian tube and peritoneal cancer: A double-blind randomized controlled trial.

AIM: To compare the efficacies and side effects of intravenous and oral dexamethasone (IV-D and PO-D) for paclitaxel-associated hypersensitivity reaction (P-HSR) prophylaxis in patients with primary ovarian, fallopian tube and peritoneal carcinomas (POC/PFTC/PPC) receiving a first cycle of paclitaxel plus carboplatin (TC). METHODS: In this double-blind randomized controlled trial, patients with POC/PFTC/PPC receiving a first cycle of TC were randomly allocated in a 1:1 ratio to either the IV-D or PO-D groups. Those were followed at 28 days. Primary outcomes were incidence of overall and severe P-HSRs. Secondary outcomes included incidence of dexamethasone-related side effects, other chemotherapy-related adverse events (AEs), and quality-of-life (QoL). RESULTS: A total of 288 patients were enrolled from February to July 2015, of whom 281 were eligible for analysis, including 140 allocated to IV-D and 141 to PO-D. There was no significant difference in P-HSR rate between the IV-D and PO-D groups (17.9% vs. 19.1%, P = 0.780). Severe P-HSR occurred in one women in the IV-D group (0.7% vs. 0%, P = 0.498). There were no significant differences in other chemotherapy-related AEs and QoL scores. However, women in the PO-D had more side effects from short-term corticosteroid use than those in the IV-D group, especially acne (10.6% vs. 2.1%, P = 0.004). CONCLUSIONS: IV-D and PO-D have similar efficacies for preventing P-HSR. However, short-term IV-D may be associated with fewer side effects than PO-D. IV-D is thus suggested for P-HSR prophylaxis in patients with POC/PFTC/PPC receiving a first cycle of TC.

Rajavithi-ovarian cancer predictive score (R-OPS): A new scoring system for predicting ovarian malignancy in women presenting with a pelvic mass.

OBJECTIVE: To develop a new scoring system based on menopausal status, ultrasound (US) findings, serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to predict ovarian cancer (OC) in women presenting with a pelvic or adnexal mass. METHODS: Consecutive female patients aged over 18years with pelvic or adnexal masses investigated preoperatively by pelvic US, serum CA125 and HE4 who underwent elective surgery were enrolled. The "Rajavithi-Ovarian Cancer Predictive Score (R-OPS)" was developed using data from 2012 and validated using data from 2013 to 2014. The diagnosis of OC was based on pathological findings. Data were analyzed by logistic regression and area under the receiver operating characteristic curve (ROC-AUC). RESULTS: Based on a development set of 260 women including 74 with OC, menopausal status (M), serum CA125 and HE4, and US findings of solid lesions (U) were identified as significant predictors of OC. R-OPS=M×U×(CA125×HE4)(1/2) revealed good calibration (goodness-of-fit test, p=0.972) and discrimination (ROC-AUC=92.8%). Performance validation in 266 women, 82 with OC, showed good discrimination with ROC-AUC of 94.9%. Performance in the validation sample with a cutoff value of R-OPS>330 revealed sensitivity, specificity, and positive and negative predictive values of 93.9%, 79.9%, 67.5%, and 96.7%, respectively. CONCLUSIONS: The new R-OPS scoring system showed good discrimination between non-cancerous lesions and OC. However, a prospective study in a different setting is required to confirm these preliminary data.

Diagnostic Accuracy and Optimal Cutoff Value of Serum HE4 to Predict Ovarian Cancer in Thai Women with Pelvic Masses.

Background: Serum human epididymis protein 4 (HE4) is highly expressed in women with ovarian cancers (OCs), but data about its clinical application of HE4 for Thai women is limited. Objective: To evaluate the diagnostic accuracy and optimal cutoff for HE4 in distinguishing benign lesions, borderline ovarian tumor (BOTs), and OCs compared with CA125 in Thai women at Rajavithi Hospital. Material and Method: The cross-sectional study was conducted in Thai women aged older than 18 years old with pelvic masses whom underwent elective surgery at Rajavithi Hospital between 2012 and 2013. Preoperative serum HE4 and CA125 levels were measured and pathologic specimens were reviewed. Results: Of the 518 participants evaluated, 316 had benign lesions, 43 had BOTs, and 159 had OCs. Between non-cancers and OCs, area under receiver operating characteristic curve (ROC-AUC) for HE4 hardly differed from CA125 (0.85 vs. 0.83, p = 0.402) but was significantly lower in postmenopausal women (0.79 vs. 0.86, p = 0.049). The optimal cutoff value of HE4 was 72 pM/L for all menopausal status. Lower HE4 was seen in 30.8% of mucinous carcinoma and 31.7% of clear cell carcinoma. The HE4 ROC-AUC was significantly higher than CA125 ROC-AUC in distinguishing benign diseases and BOTs (0.71 vs. 0.53, p<0.001), HE4 in 70% of BOTs was 51 to 95 pM/L. Conclusion: Although the 72 pM/L cutoff for HE4 was appropriate in distinguishing between non-cancers and OCs for both pre- and postmenopausal women, the limitation for postmenopausal women, mucinous carcinomas, and clear cell carcinomas require to be complemented with CA125.

Risk factors of pelvic lymph node metastasis in cervical adenocarcinoma following radical hysterectomy and pelvic lymphadenectomy.

BACKGROUND: Lymph node metastasis is the most important prognostic factor in cervical cancerpatients. However, most of the available knowledge about risk factors of pelvic nodal metastasis in cervical cancer has come from studies in which the majority of patients had the squamous cell carcinoma (SCC) subtype. OBJECTIVE: To determine the risk factors of pelvic lymph node metastasis in early-stage cervical adenocarcinoma (AC) patients following radical hysterectomy and bilateral pelvic lymphadenectomy. MATERIAL AND METHOD: Retrospective reviews were carried out of the medical charts and pathologic slides of 251 patients with cervical AC stage IB1-IIA who underwent radical hysterectomy and bilateral pelvic lymphadenectomy at Rajavithi Hospital from January 1, 2000 to December 31, 2011. The risk factors of pelvic lymph node metastasis were analyzed by multiple logistic regression. RESULTS: Of the 251 patients, pelvic node metastasis in stage IB1-IIA cervical AC was detected in 29 patients (11.6%). Multivariable analysis revealed that clinical stage IB2-IIA (adjusted OR 3.4, 95%CI 1.2-9.7), tumor size more than 2 cm (adjusted OR 3.5, 95%CI 1.1-11.8), and positive lymphovascular invasion (LVSI) (adjusted OR 55.5, 95%CI 7.2-427.6) were significantly associated with pelvic nodal metastasis. Early-stage cervical AC patients with no risk factor, one risk factor other than LVSI, LVSI factor alone, two risk factors, and three risk factors were identified as having pelvic nodal metastasis in 0%, 2.3%, 9.1%, 29.1% and 58.8% of cases respectively. CONCLUSION: Clinical stage IB2-IIA, tumor size of more than 2 cm, and positive LVSI were significant risk factors for pelvic nodal metastasis in early-stage cervical AC patients. Those with no risk factors were not found to have pelvic nodal metastasis and might be candidates for less radical surgery, whereas patients with the presence of LVSI and/or 2 other risk factors were found to be at high risk of pelvic node metastasis and might benefit from extensive lymphadenectomy and adjuvant therapy.

The efficacy of neoadjuvant paclitaxel-carboplatin chemotherapy followed by radical hysterectomy compared to radical hysterectomy alone in bulky stage IB2-IIA cervical cancer.

OBJECTIVE: To compare the efficacy of neoadjuvant paclitaxel-carboplatin chemotherapy followed by radical hysterectomy with radical hysterectomy alone in patients with bulky cervical cancer stage IB2-IIA. MATERIAL AND METHOD: From January 2000 through December 2009, 80 patients with bulky cervical cancer stage IB2-IIA that received neoadjuvant paclitaxel-carboplatin chemotherapy (n = 40) or immediate primary surgery (n = 40) were reviewed. The efficacy of neoadjuvant chemotherapy on the basis of feasibility in operation and pathological prognostic factors and the percentage of patients who needed postoperative adjuvant concurrent chemoradiation therapy were compared. RESULTS: There were no significant differences between group in age, tumor size, FIGO staging, histologic type and grading at the time of diagnosis. All patients in neoadjuvant chemotherapy group successfully underwent radical hysterectomy. The pathological findings included tumor size, deep cervical invasion, parametrial involvement, positive surgical margin and lymphovascular space invasion were statistically significant decrease in neoadjuvant chemotherapy group. Nevertheless, the pelvic nodal metastasis was not different between both groups. Adjuvant concurrent chemoradiation therapy had a statistically significant decrease in the neoadjuvant chemotherapy group. CONCLUSION: Neoadjuvant chemotherapy significant by improves the feasibility in operation and the pathological prognostic factors, and decreases the percentage of patients who needed postoperative adjuvant concurrent chemoradiation therapy.

Role of adjuvant radiotherapy after radical hysterectomy in node-negative stage IB-IIA cervical cancer with intermediate risk factors.

OBJECTIVE: To assess the benefit of adjuvant radiotherapy after radical hysterectomy in node-negative FIGO stage IB-IIA cervical cancer patients with intermediate risk factors. MATERIAL AND METHOD: Medical records of FIGO stage IB-IIA cervical cancer patients who underwent radical hysterectomy at Rajavithi Hospital between January 2000 and December 2007 with negative pelvic node were reviewed. Of the 573 node-negative stage IB-IIA cervical cancer patients, 115 had at least one of the intermediate risk factors; 18 cases received adjuvant radiotherapy (RT group) while 97 patients did not receive (non RT group). Recurrence-free survival and complications of combined treatment of each group were investigated. RESULTS: The median follow-up period was 62.5 months (range 5-119 months). Of the 115 patients with any of the intermediate risk factors, 56 (48. 7%) had single intermediate risk factor and 59 (51.3%) had two or more intermediate risk factors. Sixteen patients (13.9%) developed recurrence, 6 at the locoregional site, 5 at the distant sites and 5 at synchronous sites. Eleven patients (18.6%) who had two or more intermediate risk factors developed recurrences. In the RT group, 3 patients (20.0%) developed recurrences whereas 8 patients (18.2%) in the non RT group developed recurrences (p = 0.574). The 5-year recurrence free survival rates in patients with two or more risk factors received adjuvant radiotherapy and those without adjuvant radiotherapy were 77.8% and 83.0%, respectively (p = 0.904). No locoregional recurrence occurred in patients who received adjuvant radiotherapy. Three patients had treatment related complications (2 with leg lymphedema and 1 with radiation proctitis). CONCLUSION: Postoperative radiotherapy in node-negative stage IB-IIA cervical cancer patients with intermediate risk factors reduced only the incidence of locoregional recurrence. Distant recurrence was the major pattern of treatment failure after adjuvant radiotherapy.

Thermal artifact after three techniques of loop excision of the transformation zone: a comparative study.

AIMS: To compare a surgical-margin thermal artifact in 3 techniques of loop excision of the transformation zone (LETZ). METHODS: The histopathologic specimens from 140 patients who underwent 3 techniques of LETZ with different electrosurgical units (large loop used with a Valleylab, large loop used with an Ellman Surgitron, and contoured loop with a Utah Finesse) performed in Rajavithi Hospital between January 2003 and June 2007 were reevaluated by one pathologist with regard to degree and width of diathermy artifact. RESULTS: All of the specimens exhibited thermal tissue artifacts but there were varying degrees of extent and severity. Overall, the mean thermal artifact zone was 0.85 ± 0.94, 0.57 ± 0.47, and 0.49 ± 0.51 mm for the endocervical margin, ectocervical margin, and stromal margin, respectively. However, the thermal artifact did not interfere with the histological diagnosis or the assessment of the margins in all cases. There were no statistical differences in the thermal artifact measurements in the 3 groups. The 3 LETZ techniques provided comparable thermal artifacts in terms of qualitative and quantitative measurement. CONCLUSIONS: The thermal artifacts, both in severity and extent, are not significantly different in the 3 LETZ techniques. For routine LETZ in clinical practice, those techniques can be used with a comparable outcome.