Verification of HPV16 as a good prognostic factor for cervical adeno-adenosquamous carcinoma via an international collaborative study.

OBJECTIVE: This study (Asian Gynecologic Oncology Group [AGOG]13-001/Taiwanese Gynecologic Oncology Group [TGOG]1006) was to validate human papillomavirus (HPV)16 as an independent good prognostic factor and investigate the impact of treatment modalities to cervical adenocarcinoma and adenosquamous carcinoma (AD/ASC). MATERIALS AND METHODS: Patients receiving primary treatment at AGOG and TGOG member hospitals for cervical AD/ASC were retrospectively (1993-2014) and prospectively (since 2014) enrolled. DNA extraction from paraffin-embedded tissue (FFPE) specimens was used for HPV genotyping. Those with suspected endometrial origin were excluded for analysis. RESULTS: A total of 354 patients with valid HPV results were enrolled, 287 (81.1%) of which had HPV-positive tumors. The top-3 types were HPV 18 (50.8%), HPV16 (22.9%) and HPV45 (4.0%). The HPV16-negativity rates varied widely across hospitals. 322 patients were eligible for prognostic analyses. By multivariate analysis, advanced stage (HR5.8, 95% confidence interval [CI] 2.1-15.8; HR5.8, 95% CI 1.6-20.5), lymph node metastasis (HR4.6, 95% CI 2.7-7.9; HR7.3, 95% CI 3.8-14.0), and HPV16-positivity (HR0.3, 95% CI 0.1-0.6; HR0.3, 95% CI 0.1-0.9) were independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Stage I patients with primary surgery had better 5-year PFS (82.8% vs 50.0% p = 0.020) and OS (89.3% vs 57.1%, p = 0.017) than those with non-primary surgery, while the propensity scores distribution were similar among the treatment groups. CONCLUSION: This study confirmed that HPV16-positivity was a good prognostic factor for PFS and OS in AD/ASC, and patients seemed to have better outcome with primary surgery than non-primary surgery.

Clinicopathologic Features and Treatment Outcomes in Patients with Stage I, High-Risk Histology or High-Grade Endometrial Cancer after Primary Staging Surgery: A Taiwanese Gynecologic Oncology Group Study.

To investigate the clinicopathological features and treatment outcomes in patients with stage I, high-risk endometrial cancer. Patients with International Federation of Gynecology and Obstetrics stage I, papillary serous, clear cell, or grade 3 endometrioid carcinoma treated between 2000 and 2012 were analyzed for the clinical and pathological factors in relation to prognosis. A total of 267 patients (stage IA; n = 175, stage IB; n = 92) were included. Among the clinicopathological features, stage and age were significant prognostic factors. The recurrence rate and overall survival for stage IB versus IA were 22.8% versus 9.1% (p = 0.003) and 149.7 months versus 201.8 months (p < 0.001), respectively. The patients >60 years of age also had a higher recurrence rate (21.7% versus 9.7%, p = 0.008) and poorer survival (102.0 months versus 196.8 months, p = 0.001) than those ≤60 years of age. Distant recurrence (64.9%) occurred more frequently than local recurrence (24.3%) and local combined with distant recurrence (10.8%) (p < 0.001). The postoperative treatment modality had no impact on tumor recurrence rate, recurrence site, or overall survival. Distant recurrence is a major cause of treatment failure in patients with stage I, high-risk endometrial cancer. However, current adjuvant treatment appeared to have little effect in preventing its occurrence.

Risk factors in progression from endometriosis to ovarian cancer: a cohort study based on medical insurance data.

OBJECTIVE: The objective was to identify risk factors that were associated with the progression from endometriosis to ovarian cancer based on medical insurance data. METHODS: The study was performed on a dataset obtained from the National Health Insurance Research Database, which covered all the inpatient claim data from 2000 to 2013 in Taiwan. The International Classification of Diseases (ICD) code 617 was used to screen the dataset for the patients who were admitted to hospital due to endometriosis. They were then tracked for subsequent diagnosis of ovarian cancer, and available biological, socioeconomic and clinical information was also collected. Univariate and multivariate analyses were then performed based on the Cox regression model to identify risk factors. C-index was calculated and cross validated. RESULTS: A total of 229,617 patients who were admitted to hospital due to endometriosis from 2000 to 2013 were included in the study, out of whom 1,473 developed ovarian cancer by the end of 2013. A variety of factors, including age, residence, hospital stratification, premium range, and various comorbidities had significant impact on the progression (p<0.05). Among them, age, urbanization of residence, hospital stratification, premium range, post-endometriosis childbearing, pelvic inflammation, and depression all had independent, significant impact (p<0.05). The validated C-index was 0.69. CONCLUSION: For a woman diagnosed with endometriosis, increased age, residing in a highly urbanized area, low or high income, depression, pelvic inflammation, and absence of childbearing post-endometriosis all put her at high-risk to develop ovarian cancer. The findings may be of help to gynecologists to identify high-risk patients.

The Exploration of Health-Related Quality of Life.

The purpose of this study was to explore quality of life (QoL) and the factors influencing QoL in gynecological cancer patients. One hundred sixty-seven patients with gynecologic cancers were recruited from a district hospital in Southern Taiwan. The instruments used included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Version 3.0 in Chinese (EORTC QLQ-C30), the Symptom Distress Scale, and demographic characteristics and disease-related variables. The results showed that the mean score for the QLQ-C30 was 61.13 ( SD = 22.71). In the stepwise regression model, two factors predicted overall global QoL: symptom distress (33.8%) and current occupation (2.2%). These predictors accounted for 36.0% of the total variance. These results showed that symptom distress was a predictor of QoL. This study provides a reference for use when designing improved educational care programs that reduce patient symptom distress and enhance gynecologic cancer patients' QoL.

PAX1 methylation as a potential biomarker for cervical cancer screening.

OBJECTIVES: DNA methylation is a potential biomarker for early cancer detection. Previous studies suggested that the methylations of several genes are promising markers for the detection of cervical intraepithelial neoplasia at grade III or worse (CIN3+). The purpose of the present study was to explore the feasibility of these DNA methylation testing in cervical cancer screening. METHODS: A total of 443 women were recruited from the Yuan's General Hospital. Cervical scrapings were collected for Papanicolaou (Pap) test by using cervical brushes, and the cytological data were used for analysis. The residual cells on the brush were preserved in phosphate-buffered saline solution at 4°C until DNA extraction. Then, the extracted DNA were used for molecular tests, which included human papillomavirus typing and quantification of the methylation levels for PAX1, SOX1, and NKX6-1 genes. Subjects who had abnormal Pap test results underwent colposcopy or biopsy with subsequent conization or major surgery when biopsy results revealed CIN2+. The final diagnosis for this group was confirmed by colposcopy or pathological examination. The study was approved by the institutional review board of Yuan's General Hospital, and all the molecular tests were performed by ISO17025 certified laboratories. RESULTS: The sensitivity of PAX1 and SOX1 was greater than 80%, and the specificity of PAX1 and NXK6-1 was greater than 80% for the detection of CIN3+ lesions. PAX1 detection alone had a sensitivity and specificity of 86% and 85%, respectively, whereas when used as a cotest with the Pap test, the sensitivity and specificity were 89% and 83%, respectively. CONCLUSIONS: PAX1 showed great potential as a biomarker for cervical cancer screening. When incorporating PAX1 detection into current screening protocol, the efficacy of screening could be greatly improved. Moreover, unnecessary referral for colposcopy and biopsy could be reduced up to 60%. However, prospective population-based studies are necessary for further implementation of this screening program.

Modified novel technique for improving the success rate of applying seprafilm by using laparoscopy.

STUDY OBJECTIVE: To describe a modified surgical procedure for applying the adhesion barrier Seprafilm laparoscopically. DESIGN: Retrospective analysis with videos and illustrations showing laparoscopic application of Seprafilm. SETTING: University hospital. PATIENTS: Women undergoing fertility-sparing laparoscopic surgery (myomectomy, endometriotic ovarian cyst or dermoid cyst enucleation, and tuboplasty) via a modified technique. INTERVENTION: Two layers of Seprafilm with plastic covering were rolled together and delivered through a 10-mm trocar, and an irrigation tube was used to moisten the Seprafilm and cover the irregular postoperative rough surface of the organ. After application of Seprafilm, the patient was placed in a reverse Trendelenburg position to check whether the Seprafilm remained in situ on the target surgical surface to act as a physical barrier to adhesion development. MEASUREMENTS AND MAIN RESULTS: After changing the patient's position, illustrations and videos showed that the Seprafilm remained on the postoperative surgical surface, creating a site-specific physical barrier. On day 4 after myomectomy, second-look laparoscopy in 2 patients showed that the Seprafilm had become gel-like and remained between the intestine and posterior rough surface of the uterus. There were no systemic second-look laparoscopic data. CONCLUSION: It is feasible and easier to apply Seprafilm adhesion barrier laparoscopically using the modified technique. Further studies are warranted to prove its efficacy after such use.

Post-coital vaginal douching is risky for non-regression of low-grade squamous intraepithelial lesion of the cervix.

BACKGROUND: Vaginal douching is a common practice worldwide. Its effect on the natural history of the early lesion of human papillomavirus (HPV) infection, low-grade squamous intraepithelial lesion (LSIL), is unknown. METHODS: In a prospective nation-wide cohort (n=1332), epidemiological variables including habit of vaginal douching after intercourse and outcomes of LSIL were studied. Colposcopy-confirmed LSIL women (n=295) were followed every 3 months. Parameters of HPV infection, sexual behavior, personal hygiene and environmental exposures were compared with the follow-up outcomes. RESULTS: There was a 15% chance of HSIL co-existing with the LSIL cytology result. Eight percent of colposcopy-confirmed LSIL were found with HSIL in 1 year. With a follow-up of up to 36 months, 83% LSIL regressed, 11% progressed and 6% persisted. The mean time (95% CIs) to regression and progression were 5.2 (4.7-5.8) and 8.0 (5.8-10.3) months, respectively. Risk factors of the non-regression of LSIL included HPV prevalence on enrollment, habit of vaginal douching after intercourse with a hygiene product and non-regular Pap screening, with odd ratio of 4.4 (1.9-10.3), 3.14 (1.04-9.49) and 2.12 (1.24-3.62), respectively. HPV prevalence and vaginal douching also conferred a slower regression of LSIL (8.0 vs. 4.1 months, P<.001 and 8.0 vs. 5.6 months, P=0.02, respectively). CONCLUSION: The study disclosed a transient but warning nature of cytological LSIL. Practicing of vaginal douching after intercourse, especially with hygiene products, is associated with non-regression of LSIL.

Successful management of a pregnant woman with HELLP syndrome, pulmonary edema, postpartum hemorrhage and acute renal failure, using early hemodialysis, intravenous immunoglobulin and noninvasive monitoring: a case report.

BACKGROUND: HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) with medical complications is a major cause of maternal mortality in pregnancy. A vicious cycle may occur without expeditious delivery and proper management. CASE: A woman with severe HELLP syndrome, hemolytic renal failure, pulmonary edema and postpartum hemorrhage was successfully managed using early hemodialysis, intravenous immunoglobulin (IVIG) and noninvasive hemodynamic monitoring. CONCLUSION: Pulmonary edema is easily managed by early hemodialysis. IVIG may be a viable treatment for thrombocytopenia and hemolysis but can induce reversible interstitial nephritis and membranous glomerulonephritis.

"Silent" rupture of unscarred gravid uterus with subsequent pelvic abscess: successful laparoscopic management.

Intrapartum rupture of an unscarred uterus is rare in current times. However, it is still associated with significant maternal and fetal mortality and morbidity. Unlike rupture or dehiscence of a previous cesarean scar, which is occasionally bloodless, complete rupture of a gravid unscarred uterus frequently results in fetal jeopardy and significant maternal intraperitoneal bleeding, causes acute abdomen, and demands emergency surgical (laparotomy) intervention. Laparoscopy generally has no role in such circumstances due to the generally unstable maternal hemodynamic condition and the necessity of prompt fetal delivery with an abdominal approach. We present a rare case of intrapartum rupture of an unscarred gravid uterus with an atypical insidious clinical course. The diagnosis of complete uterine rupture was made 20 days after the patient's successful vaginal delivery, at which time a large pelvic abscess formed. The condition was successfully managed laparoscopically. Successful vaginal delivery, even with normal lochia, good uterine contraction, and stable vital signs, does not preclude the possibility of uterine rupture. For patients with unusual postpartum pelvic pain, uterine rupture should be considered as one of the possible etiologic factors, and prompt survey should be performed. Laparoscopic intervention may be valuable in such situations.

Very large yolk sac and bicornuate uterus in a live birth.

Pregnancies with a very large yolk sac are generally always associated with poor outcomes. Herein, we present a case in which a very large yolk sac (mean diameter, 8.1 mm) and a bicornuate uterus were shown on transvaginal sonography in the first trimester, but which resulted in a live birth. To our knowledge, this is the largest yolk sac among all cases accompanying live births which have been published in the literature. The unusual enlargement of the yolk sac may be secondary to the compensation effect for the poor blood supply in the medial wall of the bicornuate uterus for the conceptus. To predict the outcome of pregnancy, based on this case report, the quality of the yolk sac might be more important than its size.

The feasibility of low-dose CT for pulmonary metastasis in patients with primary gynecologic malignancy.

PURPOSE: To assess the feasibility of low-dose CT (LDCT) in the detection of pulmonary metastases in patients with primary gynecologic malignancies and also to compare the performance of chest digital radiography (DR) and LDCT for their delectability of pulmonary metastases, with use of standard-dose CT (SDCT) as the reference standard. MATERIALS AND METHODS: Thirty female patients with primary gynecologic malignancies (age range, 20-76 years; mean age, 50 years) underwent DR, noncontrast LDCT and contrast-enhanced SDCT, which were performed within an interval of 2 weeks. We used lung nodule, mediastinal lymphadenopathy (>10 mm in the short axis) and pleural changes (including effusion, irregular thickening, or nodularity) as the cardinal imaging findings of lung metastases. A five-point scoring system was designed to indicate the probability of lung metastasis from primary gynecologic malignancies. The five-point scores of DR, LDCT, and SDCT were analyzed by receiver operating characteristic (ROC) curve. RESULTS: SDCT probability scores of +2 and -2 were set to indicate true positive and true negative for pulmonary nodule, mediastinal lymphadenopathy, and pleural effusion, respectively. All the areas under the ROC curve of LDCT appeared to be larger than those of DR[pulmonary nodule: 0.96 [95% confidence interval (CI): 0.92-1.01] vs. 0.74 [95% CI: 0.57-0.91], 0.82 [95% CI: 0.70-0.95] vs. 0.61 [95% CI: 0.50-0.77]; mediastinal lymphadenopathy: 0.98 [95% CI: 0.93-1.03] vs. 0.90 [95% CI: 0.79-1.01], 0.94 [95% CI: 0.82-1.06] vs. 0.66 [95% CI: 0.44-0.88]; and pleural effusion: 0.98 [95% CI: 0.93-1.03] vs. 0.56 [95% CI: 0.29-0.82], 0.90 [95% CI: 0.74-1.05] vs. 0.46 [95% CI: 0.23-0.68]]. CONCLUSION: The performance of LDCT were comparable to those of SDCT and superior to those of DR for detection of pulmonary nodule, mediastinal lymphadenopathy, and pleural effusion. By using LDCT, there was no need of intravenous contrast injection and less radiation exposure. We propose a protocol including standard-dose abdominal CT and low-dose chest CT for the initial and follow-up stagings of primary gynecologic malignancy. The use of chest DR is unnecessary.

Prenatal sonographic findings in a fetus with congenital isolated ileal atresia.

Most cases of isolated nonduodenal bowel atresia are thought to be due to ischemic events from hypotension, vascular accident, volvulus, intussusception and cocaine. We present a case of isolated ileal atresia suggested using results of prenatal sonography which showed multiple markedly dilated fluid-filled intestinal loops with changeable shapes and positions secondary to active peristalsis. Postnatal oral contrast radiography demonstrated obstruction located at the ileal level. Exploratory laparotomy confirmed isolated ileal atresia. Primary end-to-end anastomosis was done. The infant endured the procedure well. Cases with multiple intestinal atresia always have fatal prognosis, even after surgery. Cases of isolated intestinal atresia usually have better prognosis and deserve more attention. Early diagnosis and early intervention are both important for good outcomes.