Successful delayed delivery of the second twin by evacuating the cord prolapsed first fetus and emergent cerclage: a report of 2 cases.

BACKGROUND: In twin pregnancies, the cord prolapse of either fetus during the pre-viable period leads to fetal death but can also cause an intrauterine infection, leading to death or prematu-re birth of the remaining fetus. However, there are no validated protocols to prolong the gestational period or decrease the morbidity and mortality of the remaining fetus. CASE PRESENTATION: The present cases were PPROM and cord prolapse very early during the second trimester (around 17 weeks in the first case and 19 weeks in the second case). The first fetus was evacuated, and cervical cerclage was performed at 23 and 20 weeks in the two cases, respectively. After maintaining the pregnancy, the second baby was born around 27 and 39 weeks in the first and second cases, respectively. The delivery interval between the first and second fetuses was 46 days in the first case and 126 days in the second case. CONCLUSION: If cord prolapse is identified at a pre-viable time in twin fetuses, evacuation and cerclage should be performed as soon as possible after the cord prolapse to reduce intrauterine infection and increase the survival chances of the remaining fetus.

Fenofibrate Exerts Anticancer Effects on Human Cervical Cancer HeLa Cells via Caspase-Dependent Apoptosis and Cell Cycle Arrest.

OBJECTIVE: In the present study, we attempted to identify the effects of fenofibrate on human cervical cancer cells. METHODS: The cytotoxicity of fenofibrate in cervical cancer cells was determined by Cell Counting Kit-8. Immunoblotting assay was used to determine the protein expression of caspase-3, poly ADP-ribose polymerase cleavage, B-cell lymphoma 2 family protein expression, microtubule-associated protein 1A/1B-light chain 3 (LC3), as well as cyclins and cyclin-dependent kinases. Immunofluorescence imaging was used to determine the expression of cleaved caspase-3 and LC3. Flow cytometry was used to determine cell cycle and apoptosis. RESULTS: We first showed that fenofibrate treatment reduced cell viability in HeLa cervical cancer cells in a dose-dependent manner at 24 h and 48 h. Importantly, fenofibrate-induced cell death was mediated through cell cycle arrest in the G0-G1 phase and caspase-dependent apoptosis. Moreover, fenofibrate also induced autophagy activation in a dose-dependent manner and pharmacological inhibition of autophagy led to increase of sub-G1 phase and caspase-dependent cell death in HeLa cells. CONCLUSION: In conclusion, these data demonstrated that fenofibrate initially induced cell cycle arrest, followed by caspase-3-dependent cell death in cervical cancer HeLa cells. However, fenofibrate also induced autophagy activation, which is closely related to the survival of diverse cancer cells, thus reducing the anticancer effects of fenofibrate. Therefore, the combination of an autophagy inhibitor and fenofibrate might have the potential to become a new therapeutic strategy for cervical cancer.

Comparative performance of various human papillomavirus assays available in Korea for detecting cervical intraepithelial neoplasia.

AIM: The aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea. METHODS: Eligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher. RESULTS: A total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9-44.1) in patients positive for HPV 16/18. The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p < 0.05) compared to Cobas 4800, in aspect of high-risk HPV positive, Anyplex II HPV28 showed increased sensitivity (96.9%, p < 0.05). CONCLUSION: The performance of the HPV genotype test that were commonly used in Korea was concordant with Cobas HPV test. Further studies are needed to evaluate the safety, efficiency, and cost-effectiveness of the various commercially available domestic HPV assays.

Discrepancy between Cytology and Histology in Cervical Cancer Screening: a Multicenter Retrospective Study (KGOG 1040).

BACKGROUND: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells. Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. METHODS: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. RESULTS: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7 (19-88) years and mean BMI was 22.5 (16.9-34.1) kg/m². The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475-3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367-0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385-2.469). CONCLUSION: Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Dual oxidase 1 and NADPH oxidase 2 exert favorable effects in cervical cancer patients by activating immune response.

BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) not only can promote cancer progression, but also they have recently emerged as mediators of the mucosal immune system. However, the roles and clinical relevance of the collective or individual NADPH oxidase (NOX) family genes in cervical cancer have not been studied. METHODS: We investigated the clinical significance of the NOX family genes using data from 307 patients with cervical cancer obtained from The Cancer Genome Atlas. Bioinformatics and experimental analyses were performed to examine NOX family genes in cervical cancer patients. RESULTS: Dual Oxidase1 (DUOX1) and Dual Oxidase 2 (DUOX2) mRNA levels were upregulated 57.9- and 67.5-fold, respectively, in cervical cancer patients. The protein expression of DUOX1, DUOX2, and NOX2 also identified in cervical squamous cell carcinoma tissues. Especially, DUOX1 and DUOX2 mRNA levels were significantly increased in patients infected with human papillomavirus (HPV) 16. Moreover, high DUOX1 mRNA levels were significantly associated with both favorable overall survival and disease-free survival in cervical cancer patients. High NOX2 mRNA levels was significantly associated with favorable overall survival. Gene set enrichment analyses revealed that high DUOX1 and NOX2 expression was significantly correlated with the enrichment of immune pathways related to interferon (IFN)-alpha, IFN-gamma, and natural killer (NK) cell signaling. Cell-type identification by estimating relative subsets of known RNA transcript analyses indicated that the fraction of innate immune cells, including NK cells, monocytes, dendritic cells, and mast cells, was elevated in patients with high DUOX1 expression. CONCLUSIONS: DUOX1 and NOX2 expression are associated with mucosal immunity activated in cervical squamous cell carcinoma and predicts a favorable prognosis in cervical cancer patients.

Phase I/II clinical trial of modulated electro-hyperthermia treatment in patients with relapsed, refractory or progressive heavily treated ovarian cancer.

OBJECTIVE: To determine the maximal tolerated dose (MTD) of modulated electro-hyperthermia (mEHT) treatment and to reveal whether mEHT treatment is feasible and effective as second-line therapy in recurrent and progressive ovarian cancer. METHODS: Patients were treated with mEHT with dose escalation during the first cycle (two sessions each week for three weeks) to determine the MTD. Additional cycles were carried out with the determined dose. Dose limiting toxicity (DLT) was defined grade ≥ 2: skin burns and inability to endure the hyperthermic state of the study. The Fact-O quality of life scale was used to assess health-related well-being. RESULTS: Nineteen patients with recurrent and progressive ovarian cancer were enrolled. In the first cycle of mEHT treatment, no patient developed DLT with applied power up to 110 W, 130 W, and 150 W/day; the 150 W was the maximal applied power. Stable disease was observed in only one patient (12.5%). With median progression of 4.0 months (range, 2-17 months), 18 patients (95%) demonstrated disease progression. With median overall survival of 8.0 months (range, 2-32 months), 18 patients (95%) had died. Physical well-being scores were significantly decreased over the study period, although social, emotional, and functional well-being scores did not significantly change. CONCLUSIONS: The mEHT treatment was feasible in patients with recurrent or progressive ovarian cancer without any complication and optimal dose of mEHT treatment was up to 150 W for 1 hour/day.

Effect of pretreatment with combined oral contraceptives on outcomes of assisted reproductive technology for women with polycystic ovary syndrome: a meta-analysis.

OBJECTIVE: To evaluate the effect of pretreatment with combined oral contraceptives (COC) on outcomes in women with polycystic ovary syndrome (PCOS) who underwent assisted reproductive technology for subfertility. METHODS: Two authors independently searched MEDLINE, EMBASE, and the Cochran Library to identify and review articles published from October 1995 until December 2018 according to selection criteria. Outcomes are expressed as mean difference and odds ratio (OR) in a meta-analysis model. RESULTS: A total of seven studies were included in this meta-analysis: one randomized controlled study and two prospective and four retrospective cohort studies. Meta-analysis showed that the COC pretreatment did not affect rate of clinical pregnancy (OR = 0.93, 95% confidence interval CI 0.65-1.34, I2 = 76%) or ovarian hyperstimulation syndrome (OR = 0.90, 95% CI 0.57-1.44, I2 = 0%). However, the rate of miscarriage in the COC group was significantly higher (OR = 1.33, 95% CI 1.02-1.72, I2 = 9%) and the rate of cumulative live birth was significantly lower compared with the control group (OR = 0.72, 95% CI 0.54-0.98, I2 = 55%). Subgroup analysis showed higher rates of miscarriage and lower rates of cumulative live birth in studies with a gonadotropin-releasing hormone (GnRH) antagonist protocol (OR = 1.69, 95% CI 1.17-2.44, I2 = 0% and OR = 0.38, 95% CI 0.29-0.50, respectively). CONCLUSION: Pretreatment with COC in women with PCOS before assisted reproductive technology may have an adverse effect on clinical outcomes, especially with a GnRH antagonist protocol.

Current practices of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies: an international survey of oncologic surgeons.

BACKGROUND: The goal of the study was to investigate the current clinical practices among oncologic surgeons regarding cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From September to October 2016, an online questionnaire surveyed the oncologic surgeons by email. The questionnaire included 20 multiple-choice questions of the following: eligibility for the CRS with HIPEC procedure, perioperative staging and surgery skill, assessment of residual tumors, and method used for intraperitoneal HIPEC. RESULTS: The response rate was 16% (34/217). The majority of respondents (68%) worked at a university hospital. All respondents indicated that mesenteric invasion is the most crucial factor affecting treatment decision. Most surgeons (79%) used the Sugarbaker's staging system to intraoperatively measure the extent of peritoneal invasion. The methods used to measure the extent of miliary pattern of residual tumor spread, and the amount of residual tumor after electrocauterization varied among the surgeons. Most responders (65%) used the closed system of HIPEC. CONCLUSIONS: Despite the fact that CRS HIPEC is the standard treatment for PSM, the clinical practices are very different according to each clinical situation. Nevertheless, mesenteric invasion was found to be the most important factor impacting the treatment decision-making by the majority of responders.

Relationship between uterine volume and discontinuation of treatment with levonorgestrel-releasing intrauterine devices in patients with adenomyosis.

OBJECTIVE: This study is to evaluate the relationship between the uterine volume and the failure of levonorgestrel-releasing intrauterine device (LNG-IUD) in patients with adenomyosis. METHODS: A total of 171 women with adenomysis were treated with LNG-IUD from November 2009 to December 2011. The amount of menorrhagia, degree of dysmenorrhea, and the uterine volume were compared before and after insertion of LNG-IUD, and the treatment failure of LNG-IUD was observed. RESULTS: The mean age of the participants was 42.5 years (range 29-53 years). The mean uterine volume was 158 mL (range 46-769 mL). Among the total participants, 37 (21.6 %) discontinued the treatment prematurely. There were no different characteristics between the ongoing treatment group and treatment failure group with LNG-IUD. However, there was significant difference of uterine volume between two groups (178 ± 14 and 141 ± 7 mL, P = 0.010). Based on the receiver operator characteristic analysis, the optimum cutoff value of uterine volume more than 150 mL was significantly associated with failure of LNG-IUD (area under curve: 0.763, 95 % CI 0.669-0.856). In univariate analysis, the uterine volume more than 150 mL was the only independent factor for the failure of LNG-IUD (odds ratio 6.76, 95 % CI 1.20-38.02, P = 0.030). CONCLUSION: The rate of treatment failure after LNG-IUD insertion for the patients with adenomyosis was related to the uterine volume. Specifically, the treatment failure rate of large volume uterus (>150 mL) with LNG-IUD was significantly higher than that of small volume uterus.

Development and evaluation of the Korean version of the Gynecologic Cancer Lymphedema Questionnaire in gynecologic cancer survivors.

OBJECTIVE: The purpose of this study was two-fold: first, to develop a Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) and evaluate its reliability and reproducibility and second, to examine the diagnostic efficacy of GCLQ-K in predicting lymphedema in gynecologic cancer survivors. METHODS: We designed a case-control study, and the GCLQ-K was completed by 33 gynecologic cancer survivors with lymphedema and 34 gynecologic cancer survivors without lymphedema. A follow-up GCLQ-K was completed 3weeks after the baseline questionnaire. RESULTS: The GCLQ-K showed high reliability with a Cronbach's α of 0.83 and high reproducibility with an intraclass correlation of 0.96. Of the 7 symptom clusters, 6 identified patients with lymphedema with statistical significance; identification of lymphedema using the physical functioning and infection-related symptom clusters did not reach significance. The area under the receiver operating characteristic curve (AUC) to distinguish patients with and without lymphedema was 0.868 (95% confidence interval [CI], 0.779-0.956). Following the exclusion of the physical functioning and infection-related symptom clusters, which showed poor prediction value for lymphedema, the AUC of the GCLQ-K total score further improved to 0.922 (95% CI, 0.864-0.981). CONCLUSION: The GCLQ-K was successfully developed with minimal modifications to adapt the original GCLQ to the Korean culture and showed high internal consistency and reproducibility. Moreover, gynecologic cancer survivors with and without lymphedema could be satisfactorily distinguished using the GCLQ-K. Thus, GCLQ-K was proven to be a reliable tool, capable of identifying lymphedema in Korean gynecological cancer survivors.

Outcomes and prognosis of postpartum hemorrhage according to management protocol: an 11-year retrospective study from two referral centers.

BACKGROUND: No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment. METHODS: This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26). RESULTS: Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p < 0.001, respectively). Conversely, initial heart rate and body temperature were significantly lower in group 2 (92.5 ± 21.0 vs. 109.0 ± 28.1 beat/min, p < 0.001, and 37.3 ± 0.8 °C vs. 37.0 ± 0.9 °C, p = 0.011, respectively). Logistic regression analysis identified low initial body temperature, high lactic acid level, and shock index as independent predictors of surgical intervention (p = 0.029, p = 0.027, and p = 0.049, respectively). Regarding the causes of PPH, tone was significantly more prevalent in group 1 (57.2% vs. 35.2%, p = 0.002), whereas trauma was significantly more prevalent in group 2 (24.5% vs. 39.4%, p = 0.030). Group 2 had worse overall outcomes and prognoses than group 1. The subgroup analysis showed significantly higher rates of uterine atony combined with other causes, hysterectomy, and disseminated intravascular coagulopathy in the delayed surgical intervention group than the immediate surgical intervention group (42.2% vs. 69.2%, p = 0.027; 51.1% vs. 73.1%, p = 0.049; and 17.8% vs. 46.2%, p = 0.018, respectively). CONCLUSIONS: Patients with PPH presenting with increased lactic acid levels and shock index and decreased body temperature may be surgical candidates. Additionally, immediate surgical intervention in patients with uterine atony combined with other causes of PPH could improve prognosis and reduce postoperative complications.

Transabdominal cardiophrenic lymph node dissection (CPLND) via incised diaphragm replace conventional video-assisted thoracic surgery for cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: The objective of this study is to describe the feasibility of the new approach, transabdominal CPLND, via incised diaphragm in patients with ovarian cancer by gynecologic oncologists instead of the conventional video-assisted thoracic surgery. METHODS: From November 2008 to December 2011, 11 women (10 primary and 1 recurrent ovarian cancers) underwent CPLND for the extensive cytoreductive surgeries via incised muscle of the right diaphragm by gynecologic oncologists. All ≥5 mm tumors in CPLN, which were the criterion for suspicious malignancy on preoperative axial computed tomogram, were completely resected by gynecologic oncologists. RESULTS: The median tumor size of the CPLN was 10mm (range, 7-17 mm) and metastasis was identified in 45% (5/11) of ≥5 mm CPLN on preoperative computed tomogram. The median number of harvested CPLND was 3 (range 1-12) and metastatic node was 1 (range, 0-10). There was no significant morbidity related to CPLND and mortality associated with surgery. Ten patients achieved the no gross residual disease and one patient accomplished gross residual-1, indicating residual disease measuring ≤1 cm in maximal diameter. CONCLUSION: Transabdominal CPLND via incised diaphragm is feasible as a part of the cytoreductive surgery without significant morbidities by gynecologic oncologist. This procedure could substitute the conventional video-assisted thoracic surgery.

Brain metastasis in patients with uterine cervical cancer.

AIM: The purpose of this study was to describe the features of patients with brain metastasis from cervical cancer. MATERIAL AND METHODS: The medical records of patients with cervical cancer between February 2001 and June 2011 were reviewed retrospectively. Clinical characteristics, symptoms, treatment and survival in patients with brain metastasis were analyzed. RESULTS: Eleven patients with brain metastasis from cervical cancer were identified, representing an incidence of brain metastasis in the study population of 0.45%. Median patient age at initial diagnosis of cervical cancer was 50 years (range 33-75 years). Non-squamous cell carcinoma was diagnosed in six (54.5%) of the 11 patients, with small cell carcinoma diagnosed in two patients. Ten of the 11 patients had lung-related metastasis at presentation; eight patients had lung metastasis, one had mediastinal lymph node metastasis, and one had pleural metastasis. The median interval from diagnosis of cervical cancer to identification of brain metastasis was 15.4 months (range 3.4-83.3 months). Nine patients presented with neurologic symptoms, such as headache, nausea, vomiting, seizure and extremity weakness. Initially, six patients received whole brain radiotherapy: three patients received chemotherapy; one underwent surgery; and one patient refused treatment. The median survival time after diagnosis of the brain metastases was 5.9 months (range 0.7-19 months). CONCLUSION: The prognosis after diagnosis of the brain metastasis in patients with uterine cervical cancer is poor. The small cell type and lung metastasis seem to be related with brain metastasis and may be regarded as risk factors.

Endometriosis-Related Chronic Pelvic Pain.

Endometriosis, which is the presence of endometrial stroma and glands outside the uterus, is one of the most frequently diagnosed gynecologic diseases in reproductive women. Patients with endometriosis suffer from various pain symptoms such as dysmenorrhea, dyspareunia, and chronic pelvic pain. The pathophysiology for chronic pain in patients with endometriosis has not been fully understood. Altered inflammatory responses have been shown to contribute to pain symptoms. Increased secretion of cytokines, angiogenic factors, and nerve growth factors has been suggested to increase pain. Also, altered distribution of nerve fibers may also contribute to chronic pain. Aside from local contributing factors, sensitization of the nervous system is also important in understanding persistent pain in endometriosis. Peripheral sensitization as well as central sensitization have been identified in patients with endometriosis. These sensitizations of the nervous system can also explain increased incidence of comorbidities related to pain such as irritable bowel disease, bladder pain syndrome, and vulvodynia in patients with endometriosis. In conclusion, there are various possible mechanisms behind pain in patients with endometriosis, and understanding these mechanisms can help clinicians understand the nature of the pain symptoms and decide on treatments for endometriosis-related pain symptoms.

Tailored versus conventional surgical debridement in complex facial lacerations in emergency department: A retrospective study.

Surgical debridement is an essential step in treating complex facial lacerations (CFL). As the CFL severity increases, conventional surgical debridement (CSD) of wound edges becomes difficult and may be insufficient. Because the severity and shape of each CFL vary, it is necessary to tailor the customized pre-excisional design, that is, tailored surgical debridement (TSD), for each case before performing surgical debridement. The use of TSD can enable effective debridement of CFL with higher severity. This study aimed to compare the cosmetic outcomes and complication incidence of CSD versus TSD according to CFL severity. In this retrospective observational study, eligible patients with CFL who visited the emergency department between August 2020 and December 2021 were examined. CFL severity was graded as Grades I and II. The outcomes of CSD and TSD were compared using the scar cosmesis assessment and rating (SCAR) scale, wherein a good cosmetic outcome was defined as a SCAR score of ≤ 2. The percentage of good cosmetic outcomes between the 2 groups was compared. The SCAR score and percentage of good cosmetic outcomes between the 2 groups were compared overall and by severity. For analyzing complication incidence, asymmetry, infection, and dehiscence incidence were compared. In total, 252 patients were enrolled [121 (48.0%) CSD and 131 (52.0%) TSD]. The median SCAR scores were 3 (1-5) and 1 (0-2) in all enrolled patients (P < .001), 2 (0-4), and 1 (0-1) in Grade I patients (P < .01), and 5 (4-6) and 1 (1-2) in Grade II patients (P < .001) in the CSD and TSD groups, respectively. The percentage of good cosmetic outcomes was 46.3% and 84.0% overall (P < .001), 59.6% and 85.0% in Grade I patients (P < .01), and 9.4% and 83.5% in Grade II patients (P < .001) in the CSD and TSD groups, respectively. The incidence of complications was significantly higher in the CSD group than in the TSD group, but this was limited to asymmetry. No significant difference was noted in infection or dehiscence. Compared with CSD, TSD can lead to an objectively good cosmetic prognosis at higher CFL severity and can reduce facial asymmetry occurrence.

Serum HE4 level is an independent prognostic factor in epithelial ovarian cancer.

BACKGROUND: This study was designed to determine whether serum HE4 is an independent prognostic factor in ovarian cancer patients. METHODS: We measured HE4 in pretreatment serum samples from 80 women with epithelial ovarian cancer, using an enzyme-linked immunosorbent assay. The results were correlated with clinical data. RESULTS: The median serum HE4 level in ovarian cancer patients was 98.7 (range, 80.3-222.8) pg/ml. Elevated serum HE4 levels before therapy significantly correlated with a poorer progression free survival (log-rank test, P = 0.017). Multivariate analysis revealed serum HE4 to be an independent prognostic factor for progression-free survival (P = 0.036). In multivariate regression analysis, high serum HE4 levels significantly correlated with high tumor grade and serous histology (P = 0.004 and 0.017). In addition, high serum HE4 levels were significantly associated with residual tumor size and operative time (P = 0.003 and 0.033). CONCLUSIONS: Pretreatment serum HE4 seems to be an additional factor for predicting the outcome of patients with epithelial ovarian cancer. Due to its independence from established prognostic factors, serum HE4 may provide additional prognostic information.

Phase I clinical trial of alternating belotecan and oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer.

This study was designed to determine the maximum tolerated dose and toxicity profile of belotecan in combination with oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer, fallopian tubal cancer, and primary peritoneal cancer. Belotecan (0.5 mg/m/day) was administered daily (days 1-5) followed by etoposide (50, 75 mg/day) for up to 5 days (days 6-10) every 3 weeks. Dose-limiting toxicities (DLT) were defined as follows: grade 4 neutropenia less than 1 week; either neutropenic fever less than 24 h or sepsis; grade 4 thrombocytopenia; and grade of at least 3 nonhematologic toxicity except alopecia. At the first dose level (50 mg) of etoposide, none of the three patients developed DLT, whereas DLT was observed in two of three patients at the next dose level. Thus, the dose level was reduced to 50 mg, and another three patients were enrolled. DLT was found in one of six patients who received etoposide at the dose level of 50 mg/m. Thus, the maximum tolerated dose was reached (50 mg of oral etoposide) and the trial was terminated. The response was evaluable in nine patients and an objective response was observed in four patients (44%) including two complete responses. The combined regimen of belotecan followed by oral etoposide showed promising activity in platinum-resistant or heavily pretreated ovarian cancer patients at the dose level of 50 mg of oral etoposide.

Correlation between body mass index and prevalence of hereditary nonpolyposis colorectal cancer in Korean patients with endometrial cancer.

OBJECTIVE: The purpose of the study was to investigate the relationship between body mass index (BMI) and hereditary nonpolyposis colorectal cancer (HNPCC) in Korean women with endometrial cancer. METHODS: Among 227 patients with endometrial cancer in the study population, 20 patients (8.8%) had HNPCC. The patients were divided into 2 groups based on the BMI: nonobese (BMI ≤25 kg/m) and obese (BMI >25 kg/m); then the nonobese group was subdivided into 2 groups: normal weight (BMI <23 kg/m) and overweight (BMI, 23-25 kg/m). The distributions of BMI categories were compared between patients with sporadic endometrial cancer and with HNPCC-related endometrial cancer. RESULTS: Among 207 patients with sporadic endometrial cancer, 119 (57.5%) were nonobese and 88 patients (42.5%) were obese. Of 20 patients with endometrial cancer related to HNPCC, 10 (50.0%) were nonobese and 10 (50.0%) were obese. In a subgroup analysis of only nonobese patients, 68 patients with sporadic endometrial cancer had normal weight and 51 were overweight. On the other hand, all 10 patients with HNPCC related to endometrial cancer had normal weight. There was no significant difference between the group with HNPCC-related endometrial cancer and the group with sporadic endometrial cancer according to BMI (P = 0.221). However, BMI proportions in HNPCC related to endometrial cancer were significantly different from those in sporadic endometrial cancer (P = 0.016). Among a subgroup of nonobese patients, the proportion of normal weight was significant higher in patients with HNPCC-related endometrial cancer compared to those in sporadic endometrial cancer (P = 0.006). CONCLUSION: Body mass index was not different between sporadic endometrial cancer and HNPCC-related endometrial cancer in Koreans. However, BMI proportions in the patients with HNPCC related to endometrial cancer was significantly different from those in sporadic endometrial cancer. Specifically, among nonobese patients, the proportion of normal weight was significantly high in Korean women with HNPCC.

Acute renal failure induced by disseminated intravascular coagulopathy in a patient with adenomyosis.

Disseminated intravascular coagulation is most frequently associated with obstetric catastrophes, metastatic malignancy, massive trauma and bacterial sepsis, but relatively rarely related to benign tumors. We report on disseminated intravascular coagulopathy in a patient with significant adenomyosis and menometrorrhagia. An extremely rare case, disseminated intravascular coagulopathy developed in this benign case and was successfully treated with a hysterectomy and blood product transfusions.