HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP.

The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2.

Awareness of genetic counseling and genetic testing for hereditary gynecologic cancers among Korean healthcare providers: A survey.

We conducted a survey to evaluate the awareness of genetic counseling and testing for hereditary gynecologic cancers among Korean healthcare providers. We performed an on-the-spot survey using 29 questions on respondents' basic information, awareness of pre/post-test genetic counseling, genetic information management, and related social issues. We surveyed healthcare providers who attended the 2019 Hereditary Gynecologic Cancer Symposium organized by the Korean Society of Gynecologic Oncology. Of the 108 attendees, 85 (78.7%) participated in the survey. Among them, 45% (37/83) and 40% (33/83) did not have a separate clinic and had a dedicated team for genetic counseling in their institutions, respectively. Most respondents (60/76, 79%) recommended genetic testing for all women diagnosed with epithelial ovarian cancer. Many respondents simultaneously (20/85, 24%) or sequentially (45/85, 53%) tested for both pathogenic somatic and germline variants, whereas a few respondents (2/85, 2%) checked for only pathogenic somatic variants using tissue samples. Only 20% (17/85) of the respondents recommended genetic testing for all women with endometrial cancer; meanwhile, 68% (58/86) offered the test based on the results of the screening test or family history. Risk-reducing salpingo-oophorectomy was recommended to unaffected women with pathogenic BRCA1/2 variants by 69.4% of the respondents (59/85). Most respondents (73/85, 85.9%) needed a manual on bioethics law; a few required a clinical update of hereditary cancer (73/85, 85.9%). The awareness of genetic counseling and testing and the pattern of clinical practice for hereditary gynecologic cancers differ among institutions and regions in Korea. A discussion on these issues and the development of an integrated manual for healthcare providers are required.

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.

Mutually exclusive antiproliferative effect of cell line-specific HOX inhibition in epithelial ovarian cancer cell lines: SKOV-3 vs RMUG-S.

We aimed to discover cell line-specific overexpressed HOX genes responsible for chemoresistance and to identify the mechanisms behind HOX-induced cell line-specific chemoresistance in EOC. Ten HOX genes and eight EOC cell lines were tested for any cell line-specific overexpression that presents a mutually exclusive pattern. Cell viability was evaluated after treatment with cisplatin and/or siRNA for cell line-specific overexpressed HOX genes. Immunohistochemical (IHC) staining for HOXB9 was performed in 84 human EOC tissues. HOXA10 and HOXB9 were identified as cell line-specific overexpressed HOX genes for SKOV-3 and RMUG-S, respectively. Inhibiting the expression of cell line-specific HOX genes, but not of other HOX genes, significantly decreased cell viability. In SKOV-3 cells, cell viability decreased to 46.5% after initial 10 µM cisplatin treatment; however, there was no further decrease upon additional treatment with HOXA10 siRNA. In contrast, cell viability did not significantly decrease upon cisplatin treatment in RMUG-S cells, but decreased to 65.5% after additional treatment with HOXB9 siRNA. In both cell lines, inhibiting cell line-specific HOX expression enhanced apoptosis but suppressed the expression of epithelial-mesenchymal transition (EMT) markers such as vimentin, MMP9, and Oct4. IHC analysis showed that platinum-resistant cancer tissues more frequently had high HOXB9 expression than platinum-sensitive cancer tissues. HOXB9, which is overexpressed in RMUG-S but not in SKOV-3 cells, appeared to be associated with cell line-specific platinum resistance in RMUG-S. Inhibiting HOXB9 overexpression in RMUG-S cells may effectively eliminate platinum-resistant ovarian cancer cells by facilitating apoptosis and inhibiting EMT.

Characterization of neuraminidase inhibitor-resistant influenza virus isolates from immunocompromised patients in the Republic of Korea.

BACKGROUND: The emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemics of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission. METHODS: Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018-2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates. RESULTS: Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the respiratory tract despite oseltamivir and peramivir treatment. Through the neuraminidase inhibition assay, both viruses were found to be resistant to oseltamivir and peramivir, but not to zanamivir. Although hemagglutinin and neuraminidase phylogenetic analyses suggested that the 2 A(H1N1)pdm09 isolates were not identical, their antigenicity was similar to that of the 2018-19 influenza vaccine virus. CONCLUSIONS: Our data indicate the utility of monitoring influenza-infected immunocompromised patients in general hospitals for the early detection of emerging neuraminidase inhibitor-resistant viruses and maintaining continuous laboratory surveillance of patients with influenza-like illness in sentinel clinics to monitor the spread of such new variants. Finally, characterization of the virus can inform the risk assessment for future epidemics and pandemics caused by drug-resistant influenza viruses.

Pregnancies after vaginal radical trachelectomy (RT) in patients with early invasive uterine cervical cancer: results from a single institute.

BACKGROUND: Radical tracheletomy (RT) with pelvic lymphadenectomy has become an option for young patients with early invasive uterine cervical cancer who desire to maintain their fertility. However, this operative method entails a high risk for the following pregnancy due to its radicality. METHODS: We have performed vaginal RT for 71 patients and have experienced 28 pregnancies in 21 patients. They were followed up carefully according to the follow-up methods we reported previously. Their pregnancy courses and prognoses after the pregnancy were retrospectively reviewed. RESULTS: All the vaginal RTs were performed safely without serious complications, including 6 patients who underwent the operation during pregnancy. The median time to be pregnant after RT was 29.5 months. 13 patients (46%) became pregnant without artificial insemination by husband or assisted reproductive technology. Cesarean section was performed for all of them. The median time of pregnancy was 34 weeks, and emergent cesarean section was performed for 7 pregnancies (25%). The median birth weight was 2156 g. Four patients had trouble with cervical cerclage, and they suffered from sudden premature preterm rupture of the membrane (pPROM) during the second trimester of pregnancy. We underwent transabdominal cerclage (TAC) for all of them and careful management for the prevention of uterine infection was performed. One patient had a recurrence of cancer during pregnancy. CONCLUSIONS: Both the obstetrical prognosis and oncological prognosis after vaginal RT have become favorable for pregnant patients after vaginal RT.

Enrichment of Polyglucosylated Isoflavones from Soybean Isoflavone Aglycones Using Optimized Amylosucrase Transglycosylation.

Isoflavones in soybeans are well-known phytoestrogens. Soy isoflavones present in conjugated forms are converted to aglycone forms during processing and storage. Isoflavone aglycones (IFAs) of soybeans in human diets have poor solubility in water, resulting in low bioavailability and bioactivity. Enzyme-mediated glycosylation is an efficient and environmentally friendly way to modify the physicochemical properties of soy IFAs. In this study, we determined the optimal reaction conditions for Deinococcus geothermalis amylosucrase-mediated α-1,4 glycosylation of IFA-rich soybean extract to improve the bioaccessibility of IFAs. The conversion yields of soy IFAs were in decreasing order as follows: genistein > daidzein > glycitein. An enzyme quantity of 5 U and donor:acceptor ratios of 1000:1 (glycitein) and 400:1 (daidzein and genistein) resulted in high conversion yield (average 95.7%). These optimal reaction conditions for transglycosylation can be used to obtain transglycosylated IFA-rich functional ingredients from soybeans.

Genetic Characterization of Middle East Respiratory Syndrome Coronavirus, South Korea, 2018.

We evaluated genetic variation in Middle East respiratory syndrome coronavirus (MERS-CoV) imported to South Korea in 2018 using specimens from a patient and isolates from infected Caco-2 cells. The MERS-CoV strain in this study was genetically similar to a strain isolated in Riyadh, Saudi Arabia, in 2017.

Distinct molecular evolution of influenza H3N2 strains in the 2016/17 season and its implications for vaccine effectiveness.

Influenza virus is a respiratory pathogen that causes seasonal epidemics by resulting in a considerable number of influenza-like illness (ILI) patients. During the 2016/17 season, ILI rates increased unusually earlier and higher than previous seasons in Korea, and most viral isolates were subtyped as H3N2 strains. Notably, the hemagglutinin (HA) of most Korean H3N2 strains retained newly introduced lysine signatures in HA antigenic sites A and D, compared with that of clade 3C.2a vaccine virus, which affected antigenic distances to the standard vaccine antisera in a hemagglutination inhibition assay. The neuraminidase (NA) of Korean H3N2 strains also harbored amino acid mutations. However, neither consistent amino acid mutations nor common phylogenetic clustering patterns were observed. These suggest that Korean H3N2 strains of the 2016/17 season might be distantly related with the vaccine virus both in genotypic and phenotypic classifications, which would adversely affect vaccine effectiveness.

Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708).

BACKGROUND: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer. METHODS: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes. RESULTS: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively). CONCLUSIONS: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.

Oligonol, a Low Molecular Weight Polyphenol, Enhances Apoptotic Cell Death in Ovarian Cancer Cells via Suppressing NF-κB Activation.

BACKGROUND: Oligonol, a low molecular weight polyphenol derived from lychee fruit, not only has anti-inflammatory effects in various disease conditions but also has antitumor-promoting effects. We evaluate the nuclear factor-kappa B (NF-κB)-related anticancer effect of oligonol in ovarian cancer using SKOV-3 cells. METHODS: Cell viability was examined after oligonol treatment using MTT assay and reactive oxygen species (ROS) production measurement. Subsequently, apoptotic cell death was visualized by the TdT-mediated dUTP nick-end labeling (TUNEL) method. The effect of oligonol on the NF-κB signaling pathway was evaluated using western blot analysis and luciferase activity measurement of p65, an NF-κB subunit. RESULTS: Cell viability significantly decreased after oligonol treatment of 72 h. Apoptosis-related markers were highly expressed in oligonol-treated cells, and increased apoptosis after oligonol treatment was also confirmed using the TUNEL assay. Western blotting results showed the expression of NF-κB signaling pathway factors, p-ERK, TRAF2, and p-IκBα, increased following treatment with oligonol, whereas p65 and COX-2 expression decreased. Immunofluorescence imaging results showed p65 luciferase activity in the nucleus as well as a shift to cytoplasmic expression. CONCLUSION: Oligonol treatment significantly enhances apoptotic cell death in SKOV-3 cells, with the suppression of NF-κB activation, which plays an essential role in this anticancer effect.

Molecular Diagnosis of Taenia saginata Tapeworm Infection in 2 Schoolchildren, Myanmar.

Taenia saginata is the most common human tapeworm worldwide but has been unknown in Myanmar. In 2017, fecal examination in Yangon, Myanmar, revealed eggs of Taenia species in 2 children from a monastic school. Several proglottids expelled after medication with praziquantel were morphologically and molecularly confirmed to be T. saginata tapeworms.

Three-Year Recurrence-Free Survival in Patients With a Very Low Risk of Endometrial Cancer Who Did Not Undergo Lymph Node Dissection (Tree Retro): A Korean Multicenter Study.

OBJECTIVE: Randomized studies have not demonstrated a survival benefit of routine lymph node dissection in early-stage endometrial cancer. Many surgeons nevertheless perform lymph node dissection in all patients with early-stage endometrial cancer. This study aimed to ascertain the survival outcomes of very low-risk endometrial cancer patients (by the Korean Gynecologic Oncology Group [KGOG] criteria) who did not undergo lymph node dissection. MATERIALS AND METHODS: Medical records of 156 consecutive patients who underwent surgical staging without lymph node dissection were collected from 10 institutions. All patients fulfilled the KGOG criteria: (1) endometrioid corpus cancer diagnosed by preoperative endometrial biopsy, (2) serum cancer antigen-125 level ≤35 IU/mL, (3) <50% myometrial invasion with no extension beyond the uterine corpus by magnetic resonance imaging (MRI), and (4) no lymph nodes with a short diameter ≥1.0 cm by MRI or computed tomography. Sampling of <5 nodes was allowed at a surgeon's discretion. We evaluated the 3-year recurrence-free survival (RFS) and 5-year overall survival (OS) using the Kaplan-Meier method. RESULTS: The median patient age was 52 years (range, 24-86 years). The median follow-up was 59 months (range, 0-189 months). The 3-year RFS and 5-year OS were 98.6% (95% confidence interval [CI], 96.8%-100.0%) and 98.6% (95% CI, 96.7%-100.0%), respectively. No disease-related mortality occurred. The final pathology report revealed ≥50% myometrial invasion in 29 patients (18.6%) and extension beyond the uterine corpus in 2 patients (1.3%). One patient (0.6%) was diagnosed with lymph node metastasis after lymph node sampling. Eighteen patients (11.5%) received adjuvant therapy after the final pathologic results indicated high risk. CONCLUSIONS: Very low-risk patients who did not undergo lymph node dissection had acceptable survival outcomes. Omitting lymph node dissection may be reasonable in patients satisfying the KGOG criteria.

Do fertile women have an inferior treatment for high-grade precancerous lesions?

AIM: To investigate whether a concern for future pregnancy is reflected in the extent of large loop excision of the transformation zone (LLETZ) and to assess the clinical outcome. METHODS: We reviewed the medical records of 275 women who underwent LLETZ for precancerous lesions in cervix. We divided them into two groups according to pregnancy possibility in the future: nonpotential versus potential group. The potential group was arbitrarily defined as women who met one of the following: (i) regardless of marital status, younger than 41 years with less than two parities and (ii) regardless of parity, younger than 46 years and unmarried. After propensity score matching (1:1, 44 women in each group), we compared the extent of LLETZ with respect to short-term recurrence. RESULTS: After LLETZ, similar percentages of patients were finally diagnosed with ≥CIN3 (cervical intraepithelial neoplasia 3) in the two groups (27 [61.4%] vs 32 [72.7%], P = 0.257). Notably, the largest transverse diameter of LLETZ specimen was significantly larger in the nonpotential group (2.74 ± 1.06 vs 2.37 ± 0.62 cm, P = 0.047). There were more women with exocervical resection margin involvement in the potential group than in the nonpotential group (14 [31.8%] vs 6 [13.6%], P = 0.042). However, there was no significant difference in the incidence of short-term recurrence ≥HSIL (high-grade squamous intraepithelial lesion) within 24 months after LLETZ between the two groups (1 [2.3%] vs 1 [2.3%], P > 0.999). CONCLUSION: Pregnancy possibility in the future may affect the extent of LLETZ, as assessed by the largest transverse diameter obtained. This finding may be associated with increased resection margin involvement in women with future pregnancy possibility.

Transabdominal cerclage (TAC) for patients with ultra-short uterine cervix after uterine cervix surgery and its impact on pregnancy.

AIM: Patients with an ultra-short uterine cervix as a result of large conization, repeated conization or radical trachelectomy (RT), are at high risk of preterm premature rupture of the membrane, which leads to preterm birth. We have commenced performing transabdominal cerclage (TAC) of the uterine cervix for these patients. In this study, we examined the safety of TAC and its impact on pregnancy. METHODS: We have performed TAC in 11 patients before pregnancy: in six after large cervical operations, such as repeated conization; and in five for difficulties with cervical cerclage after RT. After laparotomy, a Teflon thread was placed in the avascular space between the uterine vessels and the uterine muscle, and tied. The clinical course of the patients after TAC and their pregnancy course were retrospectively reviewed. RESULTS: TAC was performed safely without any complications. The mean operative duration was 53 ± 10 min, and the mean blood loss during the operation was 49 ± 64 mL. Seven women conceived within 2 years after TAC. Their pregnancy courses were favorable. Five of the women underwent scheduled cesarean sections, while two pregnancies are ongoing. CONCLUSIONS: Although there are risks of various complications as a result of the use of non-absorbable thread and the need for two extra laparotomies, TAC can be a safe and useful option for patients who show cervical incompetence after large uterine cervical operations, such as RT or large conization.

Identifying risk factors for occult lower extremity lymphedema using computed tomography in patients undergoing lymphadenectomy for gynecologic cancers.

OBJECTIVE: To identify risk factors for lower extremity lymphedema (LEL) using computed tomographic (CT) scan in patients undergoing lymphadenectomy for gynecologic cancers. METHODS: We retrospectively reviewed 511 consecutive gynecologic cancer patients undergoing lymphadenectomy. Mean difference (3.77±3.14mm) of subcutaneous layer thicknesses between preoperative and postoperative 1-year CT scans of 106 patients with clinical LEL was used as an objective criterion for regrouping all the patients into those with mean difference >3.77mm and ≤3.77mm. Risk factors for clinical LEL and significant increase of subcutaneous layer thickness on CT were evaluated using a logistic regression model. RESULTS: A total of 106 (20.7%) patients were clinically diagnosed with LEL by a physician. Total number of lymph nodes (LNs) retrieved >30 (Odds ratio [OR] 3.2; 95% Confidence interval [CI] 1.94-5.32; p<0.001) and adjuvant pelvic radiotherapy (OR 3.1; 95% CI 1.75-5.52; p<0.001) were risk factors for clinical LEL. One hundred-nineteen (23.3%) had subcutaneous layer thickness increase of >3.77mm. In addition to number of LNs retrieved >30 (OR 2.3; 95% CI 1.40-3.74; p=0.001) and adjuvant pelvic radiotherapy (OR 1.7; 95% CI 1.01-2.74; p=0.046), open surgery (OR 1.8; 95% CI 1.01-3.11; p=0.045), long operation time (OR 1.7; 95% CI 1.05-2.83; p=0.032), and no use of intermittent pneumatic compression (IPC) (OR 2.1; 95% CI 1.06-4.16; p=0.034) were risk factors for thick subcutaneous layer on postoperative CT. CONCLUSIONS: In addition to high LN retrieval and adjuvant pelvic radiotherapy, open surgery, long operation time, and no IPC use could be risk factors for occult LEL after lymphadenectomy in gynecologic cancers.

Favorable factors for preserving bladder function after nerve-sparing radical hysterectomy: A protocol-based validation study.

OBJECTIVES: To investigate favorable factors of nerve-sparing radical hysterectomy (NSRH) for preserving the pelvic autonomic nerves and subsequent bladder function and to compare the safety between NSRH and conventional radical hysterectomy (CRH) for cervical cancer. METHODS: We recruited 87 consecutive patients with IB1-IIA cervical cancer who underwent NSRH, and reviewed the information of 81 patients who received CRH for historical comparisons. One gynaecologic oncologist performed all operations. RESULTS: IB1 disease was the only favorable factor for unilateral or bilateral preservation (adjusted OR, 0.245; 95% CI, 0.077-0.774), whereas IB1 disease and squamous cell carcinoma (SqCC) were favorable for bilateral preservation (adjusted ORs, 0.336 and 0.116; 95% CIs, 0.162-0.982 and 0.023-0.581). The median duration of postoperative catheterization (DPC) was different among bilateral, unilateral and failed preservation (median 6 vs 18 vs 90 days; P < 0.001). The median DPC was shorter in NSRH patients with stage IB1 disease or SqCC (7 vs 14 days; P < 0.05) despite no difference between NSRH and CRH in those with IB2-IIA disease or non-SqCC. Survival was not different between NSRH and CRH patients. CONCLUSIONS: IB1 disease and SqCC are favorable for preserving the pelvic autonomic nerves and subsequent bladder function without compromising survival outcomes in patients treated with NSRH.

Magnetic Resonance Imaging as a Valuable Tool for Predicting Parametrial Invasion in Stage IB1 to IIA2 Cervical Cancer.

OBJECTIVES: The aims of study were to determine the predictive value of preoperative magnetic resonance imaging (MRI) for parametrial invasion (PMI) and to develop a predictive model for PMI in patients with stage IB1 to IIA2 cervical cancer. METHODS: We retrospectively analyzed patients with stage IB1 to IIA2 cervical cancer (n = 215) who underwent radical hysterectomy between 2003 and 2014. The presence of PMI from postoperative pathological reports and its association with preoperative MRI findings were evaluated. We developed a predictive model for PMI using independent predictive factors identified by logistic regression and estimated its predictive performance. RESULTS: Thirty patients (14.0%) had PMI from postoperative pathological reports. Among the preoperative MRI findings, a greater tumor diameter (4.2 vs 2.0 cm; P < 0.001), a larger tumor volume (92.6 vs 12.7 cm; P < 0.001), the presence of PMI (53.3% vs 8.6%; P < 0.001), and upper vaginal involvement (73.3% vs 22.7%; P < 0.001) were significantly associated with PMI. Multivariate analysis identified tumor volume (odds ratio, 7.0; 95% confidence interval, 2.63-18.53; P < 0.001) and PMI (odds ratio, 6.1; 95% confidence interval, 2.31-15.97; P < 0.001) from preoperative MRI findings as independent predictive factors for PMI. Our predictive model demonstrates that the presence of PMI or a tumor volume of greater than 18.0 cm has a higher sensitivity (86.7% vs 53.3%) and lower specificity (74.6% vs 91.4%) than the presence of PMI alone. Specifically, the model's negative predictive value was superior to that of PMI only (97.2% vs 92.3%). In the low-risk group, defined as preoperative MRI findings suggesting no PMI and a tumor volume of 18.0 cm or less, the proportion of false negative cases was just 2.8%. CONCLUSIONS: When tumor volume with findings suggesting that PMI is considered, preoperative MRI is useful in excluding PMI. A predictive model based on preoperative MRI findings seems to be valuable in identifying potential candidates for less radical surgery in stage IB1 to IIA2 cervical cancer.

Possibility of less radical treatment for patients with early invasive uterine cervical cancer.

AIM: Radical trachelectomy (RT) with lymphadenectomy has become a standard treatment modality for patients with early invasive uterine cervical cancer who hope to preserve fertility. However, pregnancy after RT has high risks of preterm birth. The possibility of more conservative RT and the application of RT for patients with higher clinical stages were studied. METHODS: The medical charts and specimens of 42 patients who underwent RT and 64 patients who underwent radical hysterectomy were retrospectively studied. Tumor size, distance between the margin of the cancer and the internal orifice of the uterus (os), parametrial invasion, lymph node metastasis and prognoses were investigated. RESULTS: The average distances between the inner margin of the cancer and the internal os were 37 mm, 29 mm, 18.7 mm and 14 mm for patients with stage 1 A2, 1B1 (≤ 2 cm), 1B1 (> 2 cm) and 1B2, respectively. When amputation was performed 10 mm below the internal os, all 10 patients with 1 A2, 57 with 1B1 (≤ 2 cm), 19 with 1B1 (> 2 cm), and one with 1B2 had a cancer-free margin > 10 mm. Patients with stage 1 A2 had a cancer-free margin > 10 mm even if we amputated the cervix 20 mm below the internal os. Parametrial invasion was detected in two patients with stage 1B1. CONCLUSIONS: A simple trachelectomy 20 mm below the internal os with pelvic lymphadenectomy might be possible for stage 1 A2 patients. The present method is best for stage 1B1 patients (≤ 2 cm). RT for stage 1B1 (>2 cm) or higher stages should be contraindicated.