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The cervical microbiome is associated with cervical cancer risk, but how microbial diversity and functional profiles change in cervical cancer remains unclear. Herein, we investigated microbial-compositional and functional differences between a control group and a high-grade cervical intraepithelial neoplasia and cervical cancer (CIN2/3-CC) group. After retrospective collection of 92 cervical swab samples, we carried out 16S rRNA amplicon sequencing on 50 and 42 samples from the control and CIN2/3-CC groups, respectively. The EzBioCloud pipeline was applied to identify the genomic features associated with the groups using 16S rRNA data. A linear discriminant analysis effect size (LEfSe) was performed to assess the enrichment in the assigned taxonomic and functional profiles. We found a lower richness in the control group relative to the CIN2/3-CC group; however, the β-diversity tended to be similar between the groups. The LEfSe analysis showed that a phylum Sacchaaribacteria_TM7, 11 genera, and 21 species were more abundant in the CIN2/3-CC group and that one uncharacterized Gardnerella species was more abundant only in the control group. Further characterization of the functional pathways using EzBioCloud showed that the 4 KEGG orthologs (Phosphotransferase system [PTS] sucrose-specific IIA, IIB, IIC components and PTS cellubiose-specific IIC component) were involved in the KEGG pathway of starch and sucrose metabolism. The two pathways of folate biosynthesis and oxidative phosphorylation were more abundant in the CIN2/3-CC group. Further confirmation of these results in larger samples can help to elucidate the potential association between the cervical microbiome and cervical cancer. [ABSTRACT FROM AUTHOR]

Tobacco smoking is established as a cofactor of human papillomavirus (HPV) for cervical cancer risk. However, the role of secondhand smoking in cervical carcinogenesis is controversial. We aimed to assess the association between secondhand smoking and high risk- (HR-) HPV persistence, a pivotal event in development of cervical cancer. In total, 9,846 women who underwent health-screening examinations from 2002 to 2011 at the National Cancer Center, Korea, were included. Secondhand smoking was defined as being exposed to secondhand smoke at home or in the workplace. Multivariate logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for risks of HR-HPV infection at baseline (N, 9,846, negative vs. positive), 1-year persistence (n, 1,237, 1-year negative vs. 1-year persistence), and 2-year persistence (n, 481, 2-year negative vs. 2-year persistence). Active smoking, secondhand smoking, and secondhand smoking in nonactive smokers had no association with these risks. Among alcohol drinkers, secondhand smoking in nonactive smokers had higher risks of HR-HPV infection at baseline (OR = 1.25, 95% CI = 1.05–1.48, p for multiplicative interaction = 0.003), 1-year persistence (1.75, 1.14–2.68, 0.004), and 2-year persistence (2.96, 1.42–6.15, 0.006), when compared to HR-HPV negative, 1-year negative, and 2-year negative categories, respectively. However, among nonalcohol drinkers, there was no association between smoking or secondhand smoking status and these risks. These findings suggest that women exposed to secondhand smoking at home or in the workplace might be at high risk of HR-HPV persistence when it is combined with alcohol drinking, even though neither active smoking nor secondhand smoking independently affects the risk. [ABSTRACT FROM AUTHOR]

Objective. The purpose of this study was to (i) determine the cervical microbial composition in different abortion samples and to (ii) investigate the correlation between spontaneous abortion and cervical microbes in Korean women. Methods. We collected cervical swabs from women who had never undergone abortion (N=36), had spontaneous abortion (N=23), and had undergone induced abortion (N=88) and subjected those samples to 16S rRNA pyrosequencing. Further, factor analysis and correlation between cervical microbiota and spontaneous abortion were evaluated by logistic regression analysis. Results. In spontaneous abortion women, 16 S rRNA gene sequences showed significant increases in Atopobium vaginae, Megasphaera spp., Gardnerella vaginalis, Leptotrichia amnionii, and Sneathia sanguinegens compared to women in nonabortion group. In multivariate logistic regression analysis, A. vaginae (OD = 11.27; 95% = 1.57–81), L. amnionii (OD = 11.47; 95% = 1.22–107.94), S. sanguinegens (OD = 6.89; 95% = 1.07–44.33), and factor 1 microbes (OD = 16.4; 95% = 1.88–42.5) were strongly associated with spontaneous abortion. Conclusions. This study showed a high prevalence of L. amnionii, A. vaginae, S. sanguinegens, and factor 1 microbes in spontaneous abortion and association with spontaneous abortion in Korean women. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study aimed to examine the combined effect of viral load and alcohol consumption on the risk of persistent high-risk (HR) human papillomavirus (HPV) infection. Methods: Among women undergoing health screening between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR-HPV infection and cytological findings of low-grade squamous intraepithelial or lower-grade lesions were followed up for 1 and 2 years, respectively. Multivariate logistic regression analysis was performed, and the relative excess risk due to interaction (RERI) and synergy index (S) were calculated. Results: Among drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.05–8.18) and 2-year persistence (OR 8.08, CI 2.36–27.6) were significantly higher for high HPV loads than for low HPV loads; this association was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89–9.05) and 2-year persistence (OR 6.61, CI 2.09–20.9) were significantly higher in subjects with a high HPV load who were also drinkers than in those who were non-drinkers. A high HPV load together with a longer drinking duration or higher alcohol consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40–6.75 or OR 2.05, CI 0.87–4.83) and 2-year persistence (OR 6.40, CI 1.72–23.8 or OR 4.14, CI 1.18–14.6). The synergistic effect of alcohol consumption and HR-HPV load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38) than on the risk of 1-year persistence (RERI = 1.21, S = 1.63). Conclusions: The synergistic effect of HR-HPV load and alcohol consumption was associated with the risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection. Limiting alcohol consumption might be an important measure to prevent the development of cervical cancer in women with a high HR-HPV load. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This prospective study was performed to evaluate the clearance of high-risk human papillomavirus (HPV) infection and incidence of cytologic abnormality and cervical intraepithelial neoplasia (CIN) during the follow-up of persistent infection in Korean women. Methods: A total of 4170 women who were screened for cervical cancer, were aged 30 years or older, had no abnormal last Pap smear results for 3 years, had no history of treatment for cervical neoplastic disease, and were not pregnant were analyzed for high-risk HPV prevalence using the Hybrid capture (HC) II assay. The 224 women with normal cytology but positive for high-risk HPV DNA using the HC-II assay were analyzed for their clearance of HPV infection. Results: The median time to clearance in women with initially normal cytology was 7.5 months from initial detection (95% CI, 5.2–9.8 months). There were significant differences in the median time to clearance (4.5 vs. 14.5 months, p <0.001) of high-risk HPV infection between women with the initial relative light unit/cutoff (RLU/CO) ratio values <10.0 and ≥10.0, as determined by the HC-II assay. In Kaplan–Meier analysis, probability of development of cytologic abnormalities, CIN and high-grade CIN was 38.2%, 21.7% and 8.5% respectively at 24 months of persistent high-risk HPV infection. Conclusion: The prevalence and clearance of high-risk infection in Korean women was similar to that in Western countries. Persistent high-risk HPV infection was associated with high viral load. [Copyright &y& Elsevier]

Abstract: Background: To evaluate the toxicity and efficacy of a newly developed topoisomerase I inhibitor, CKD-602 in second-line therapy of ovarian cancer. Methods: We enrolled 24 patients with recurrent ovarian cancer, of median age 54 years (range, 39–64). Eleven patients had measurable lesions on CT scan, and the other 13 had increased serum CA-125 levels. Eighteen patients had platinum-sensitive disease (minimum treatment free interval≥6 months) and 6 had platinum-resistant disease (minimum treatment free interval<6 months). CKD-602 (0.5 mg/m2/day) was administered intravenously for 5 days every 3 weeks. The median number of courses per patient was 6 (range, 1 to 12). Response was evaluated by the evaluation of the size of the mass by CT scan and CA-125 response. Results: The overall response rate was 45.0% (9/20), with 4 patients exhibiting partial responses and 5 patients exhibiting 75% CA-125 responses in 20 evaluable patients. Of the 9 responsive patients, 8 were platinum-sensitive (8/15, 53.3%) and 1 was platinum-resistant (1/5, 20.0%). An additional 5 patients showed stable disease, whereas 6 patients exhibited progressive lesions. Of 24 patients, the most common toxicity was hematological, with grades 3 or 4 neutropenia developing in all 24 patients (100%) and in 94 cycles (71.7%). Grade 3 thrombocytopenia developed in 4 patients (16.7%) and 6 cycles (4.6%). None of the patients experienced grades 3 and 4 gastrointestinal toxicities, including nausea, vomiting, and anorexia. Conclusions: The newly developed topoisomerase I inhibitor, CKD-602, showed activity against both platinum-sensitive and -resistant ovarian cancer, with acceptable toxicity. [Copyright &y& Elsevier]

Abstract: Objectives. : The aim of this study was to assess the safety, efficacy and impact on survival of low anterior resection and primary anastomosis at the time of en bloc resection for primary and recurrent epithelial ovarian carcinoma. Methods. : We performed a retrospective review of 46 primary and 14 recurrent epithelial ovarian carcinoma patients who underwent procedures between April 2001 and May 2005 in our center. Data were obtained from patient medical records and the cancer registry. Parameters for safety, efficacy and survival were considered as primary endpoints. Results. : For primary advanced ovarian cancer patients, 43.5% showed no visible tumor at the completion of surgery and optimal cytorection (residual tumor [RT] less than or equal 5 mm) was achieved in 89.2%. Complications associated with en bloc resection occurred in two patients (1 leakage of anastomosis site and 1 rectovaginal fistula), and these were managed with diversion colostomy. Patients with no visible residual tumor had longer disease-free survival compared to those with visible RT (median, 30 vs. 7 months; P =0.0082) and longer overall survival (3-year survival rate, 82.03% vs. 66.63%; P =0.0437). Patients with rectal invasions up to the serosa/subserosa had longer disease-free survival than those with rectal invasion up to the muscle/mucosa (P =0.0176) but did not differ significantly in terms of overall survival (P =0.0880). For recurrent ovarian cancer patients, 42.9% showed no visible tumor at the completion of surgery and optimal cytorection was achieved in 64.3%. One patient experienced an en-bloc-resection-associated complication (a rectovaginal fistula), which was managed conservatively. Patients with no visible residual tumor (RT) had longer disease-free survival than visible RT patients (median, not reached vs. 5 months; P =0.0156) but did not differ significantly in terms of overall survival (median, 32 months for no visible RT vs. 24 months for visible RT patients; P =0.0833). There were no surgery-related deaths among the overall 60 primary and recurrent ovarian cancer patients. Conclusions. : En bloc resection of primary and recurrent epithelial ovarian carcinomas with low anterior resection permits a high rate of complete debulking with acceptable morbidity and mortality rates. Patients with no visible RT after surgery had a survival advantage over patients with visible RT. [Copyright &y& Elsevier]

Abstract: Objectives. : To evaluate the efficacy of self-collected vaginal samples for high-risk HPV detection by the HPV oligonucleotide microarray method (HPVDNAChip™). Methods. : One hundred and eighteen patients with abnormal Pap smears were included. Self-collected vaginal and clinician-collected cervical samples for HPV testing were obtained. The result of the HPV DNA test was compared with the histopathological diagnosis or colposcopic finding. Results. : Of the 118 patients, 42 (35.6%) had ≥ cervical intraepithelial neoplasia (CIN) III lesions. Using the HPVDNAChip™, high-risk types of HPV were detected in 38 of these 42 patients (90.5%) with the self-collected vaginal samples and in 37 of 42 (88.1%) with the clinician-collected cervical samples. The agreement of HPVDNAchip™ results between self- and clinician-collected samples was very good (κ = 0.81) with a 93.2% concordance rate. Multiple HPV infections were found in 17 of 88 (19.3%) HPV-positive clinician-collected cervical samples. The rate of multiple HPV infection tended to decrease as the degree of pathologic classification increased. Conclusion. : Using the HPVDNAchip™ to assay for HPV infection, results from self-collected vaginal samples were compatible with those from clinician-collected cervical samples. [Copyright &y& Elsevier]

Abstract: We evaluated the accuracy of FDG-PET in diagnosing metastatic para-aortic and pelvic lymph nodes in patients with cervical cancer by comparing this noninvasive imaging technique with surgicopathologic results. We performed FDG-PET in 54 patients with cervical cancer at FIGO stages IB–IVA who were about to undergo lymphadenectomy. For region-specific comparisons, we divided the nodes into eight regions (four on each side: para-aortic, common iliac, external iliac, and internal iliac/obturator). Histological examination revealed metastases in 15 (28%) of the patients, with region-specific analysis identifying 37 (8.6%) metastases in 432 regions. The region-specific findings of FDG-PET exhibited a sensitivity of 38% and a positive predictive value (PPV) of 56%. The sensitivity increased to 52% and 65% when we restricted the pathologic criterion for metastases to tumour-invasion diameters of >5 and >10mm, respectively. These results indicate that FDG-PET exhibited low sensitivity and PPV (especially for microscopic metastases) and hence cannot replace surgical staging, although it might still be useful for detecting metastases in patients with clinical conditions that make surgical staging inappropriate. [Copyright &y& Elsevier]

Objectives. This study examines whether expression of COX-2 is associated with clinicopathological features and other molecular markers of ovarian cancer.Methods. Sixty-four paraffin-embedded tissue specimens were obtained from patients with ovarian cancer who received cytoreductive surgery and combination chemotherapy. Tissue specimens were subjected to immunohistochemical analysis using antibodies to COX-2, p53, and VEGF.Results. Increased COX-2 expression significantly correlated with histologic type (mucinous 5.6% vs. non-mucinous 65.2%, P < 0.001). COX-2 expression was also significantly associated with stage, tumor grade, residual disease status, and presence of ascites. COX-2 expression correlated positively with expression of p53 (P = 0.006) and VEGF (P = 0.025). Although survival was lower in patients with high COX-2 expression than in those without high COX-2 expression (P < 0.001), only tumor grade and stage were independent prognostic indicators. In patients with non-mucinous cancer, COX-2 expression correlated with stage (P < 0.001) and presence of ascites (P = 0.033).Conclusions. Our results suggest that expression of COX-2 in ovarian cancers is specific to histologic type of tumor and is associated with poor clinicopathologic prognostic factors. Expression of COX-2 also correlates well with expression of p53 and VEGF. [Copyright &y& Elsevier]

: ObjectivesThis study examines the relationship between expression of COX-1, COX-2, and vascular endothelial growth factor (VEGF), and their association with clinicopathological features in primary tumor and metastatic lymph node specimens from cervical cancer patients. The relationship between COX-2 expression and human papillomavirus (HPV) positivity was also examined.: MethodsThe following samples were analyzed: 97 paraffin-embedded specimens from patients with cervical cancer (Ib-IIb), including 49 primary cervical cancer specimens without lymph node metastasis and 24 primary specimens with lymph node metastasis and their metastatic lymph nodes. Immunohistochemical analysis was performed with antibodies to COX-1, COX-2, and VEGF. HPV viratype was identified by PCR and HPVDNAChip.: ResultsVEGF expression was strongly correlated with expression of COX-1 (P = 0.03) and not COX-2 (P = 0.12) in primary tumor and metastatic lymph nodes. COX-2 expression correlated with lymph node metastasis (P = 0.001), but not with any other clinicopathological features. The parametrial invasion showed borderline significance with COX-2 expression (P = 0.058). COX-1 or VEGF expression did not correlate with any clinicopathological features. In addition, COX-2 expression was not associated with HPV positivity.: ConclusionCOX-1 expression is associated with VEGF expression in primary tumor tissue and at sites of metastasis to lymph nodes. COX-2 expression is associated with lymph node metastasis and possibly parametrial invasion, but expression of COX-1 and VEGF is not associated with clinicopathological features. COX-2 expression is not associated with HPV positivity. [Copyright &y& Elsevier]

The somatic BRCA1 or BRCA2 Pathogenic Variant (PV)/Likely PV (LPV) from Next Generation Sequencing (NGS) is the most important biomarker for PARP inhibitor use and maintenance-targeted therapies. A discrepancy in the detection rates of BRCA1 and BRCA2 PV/LPV was identified among the NGS platforms. The objective of this study was to compare the somatic BRCA results from two distinct platforms using the same cohort and to identify the causes of these differences. Patients with epithelial ovarian cancer who concurrently underwent tumor NGS using two different platforms between January 2022 and June 2023 were included in this study. The two platforms used were in-house tumor NGS (Illumina NextSeq 550Dx, SureSelectXT library kit, and datasets from 1000 Genomes, ESP6500, ExAC, and ClinVar) and GreenPlan homologous recombination deficiency (HRD) test (Illumina NextSeq 550Dx, customized Twist Bioscience library kit, and datasets from COSMIC and OncoKB). The results of somatic mutations in BRCA1 and BRCA2 were compared between the two platforms. Of the 118 patients, 11.9% (n = 14) exhibited a discordant interpretation of BRCA1 or BRCA2 between the two platforms. Eleven patients (9.3%) exhibited negative results in the in-house platform but positive results (eight seven as PV of BRCA1, one as PV of BRCA2, one as LPV of BRCA1, and two as LPV of BRCA2) in the GreenPlan HRD test, while three patients (2.6%) had positive BRCA pathogenic variants (two as PV of BRCA1 [c.3340G > T, c.5152 + 3 A > C], one as LPV of BRCA2 [c.8174G > T], and one as LPV of BRCA1 [c.5017_5019delCAC]) in the in-house platform but a negative result in the GreenPlan HRD test. The discordance rate of somatic BRCA1 or BRCA2 mutations from different platforms was approximately 12%. In the case of the strong implication of BRCA PV/LPV with a negative result with one genetic test, different platforms could be considered in limited cases. Careful interpretation and further studies for the cross-validation of gene analysis platforms are needed. [ABSTRACT FROM AUTHOR]

This study aimed to validate the performance of the Korean Gynecologic Oncologic Group (KGOG)-1024 risk model in predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer (LACC). In a retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, individual risk was calculated using the KGOG-1024 risk model. The cohort was categorized into three risk groups (low-, intermediate-, and high-risk groups) according to the calculated risk. The means of the calculated and observed risks were compared within each group. The study population was classified into low-, intermediate-, and high-risk groups according to the KGOG-1024 risk model (27.2%, 49.3%, and 23.5% of patients, respectively). The calculated and observed 5-year cumulative incidence rates were 12.4% vs. 16.4% in the low-risk group, 23.2% vs. 25.9% in the intermediate-risk group, and 50.7% vs. 36.3% in the high-risk group. Overall, the calculated and observed risk was 26.7% vs. 25.6%. The KGOG-1024 risk assessment model accurately predicted distant recurrence after chemoradiation in patients with LACC, especially in the low- and intermediate-risk groups. The model may be helpful for identifying patients for future trials assessing the possible benefit of adjuvant systemic treatment after chemoradiation. • In locally advanced cervical cancer, the risk of distant failure was predicted. • The model was more accurate in subjects with a low- and intermediate- risk. • The prediction model may be useful in designing more effective trials. [ABSTRACT FROM AUTHOR]

Recent studies have reported the potential role of microbiomes in cervical disease. However, little is known about the microbiome composition and function in cervical carcinogenesis. We aimed to identify the compositional and functional alterations of cervical microbiomes in cases of cervical carcinogenesis of Korean women using shotgun metagenomic sequencing. In this study, using shotgun sequencing, we sequenced the cervical metagenomes of cervical intraneoplasia 2/3 (n = 17), cervical cancer (n = 12), and normal controls (n = 18) to identify the microbial abundances and enriched metabolic functions in cervical metagenomes. At the genus level, the microbiota of cervical cancer were differentially enriched with genera Alkaliphilus, Pseudothermotoga, and Wolbachia. Cervical intraepithelial neoplasia (CIN) 2/3 were enriched with Lactobacillus, Staphylococcus, and Candidatus Endolissoclinum. The normal group was enriched with Pseudoalteromonas and Psychrobacter. Further characterization of the functionalities of the metagenomes may suggest that six Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) that are involved in 10 pathways are associated with an increased risk of CIN2/3 and cervical cancer. Specifically, cervical metagenomes were enriched in the course of peptidoglycan synthesis and depleted by dioxin degradation and 4-oxalocrotonate tautomerase. The Cluster of Orthologous Groups (COG) category 'Defense mechanisms' was depleted in cervical cancer patients. Our findings based on shotgun metagenomic sequencing suggest that cervical microbiome community compositions and their metagenomics profiles differed between cervical lesions and normal subjects. Future studies should have larger sample sizes and/or aggregate their results to have sufficient power to detect reproducible and significant associations. [ABSTRACT FROM AUTHOR]

Background: The aim of the study is to evaluate the risk factors of anastomotic leakage (AL) and develop a nomogram to predict the risk of AL in surgical management of primary ovarian cancer. Methods: We retrospectively reviewed 770 patients with primary ovarian cancer who underwent surgical resection of the rectosigmoid colon as part of cytoreductive surgery between January 2000 to December 2020. AL was defined based on radiologic studies or sigmoidoscopy with relevant clinical findings. Logistic regression analyses were performed to identify the risk factor of AL, and a nomogram was developed based on the multivariable analysis. The bootstrapped-concordance index was used for internal validation of the nomogram, and calibration plots were constructed. Results: The incidence of AL after resection of the rectosigmoid colon was 4.2% (32/770). Diabetes (OR 3.79; 95% CI, 1.31–12.69; p = 0.031), co-operation with distal pancreatectomy (OR, 4.8150; 95% CI, 1.35–17.10; p = 0.015), macroscopic residual tumor (OR, 7.43; 95% CI, 3.24–17.07; p = 0<001) and anastomotic level from the anal verge shorter than 10 cm (OR, 6.28; 95% CI, 2.29–21.43; p = 0.001) were significant prognostic factors for AL on multivariable analysis. Using four variables, the nomogram has been developed to predict anastomotic leakage: https://ALnomogram.github.io/. Conclusion: Four risk factors for AL after resection of the rectosigmoid colon are identified from the largest ovarian cancer study cohort. The nomogram from this information provides a numerical risk probability of AL, which could be used in preoperative counseling with patients and intraoperative decision for accompanying surgical procedures and prophylactic use of ileostomy or colostomy to minimize the risk of postoperative leakage. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

We explored the prevalence of smoking, alcohol consumption, physical activity, and obesity in cervical cancer survivors and examined associations between sociodemographic factors and each health behavior. We studied 448 cervical cancer survivors ≥2 years after their initial diagnosis who had completed treatment. The total sample consisted of these survivors, and 4,480 cancer-free controls who were grouped into 5-year age cohorts and matched to the survivors in terms of both education and monthly household income. The prevalence of current smoking, current alcohol consumption, physical inactivity, and obesity in cervical cancer survivors (2.68, 23.88, 62.02, and 32.81%, respectively) did not differ significantly from those of matched non-cancer controls. Age (younger), marital status (married), and education (≥college) were associated with lower probabilities of current alcohol consumption (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.88–0.95; OR = 0.42, 95% CI = 0.23–0.78; OR = 0.49, 95% CI = 0.25–0.97, respectively). A monthly household income ≥$2,000, being employed, and self–rated health status (less healthy) were associated with physical inactivity (OR = 0.61, 95% CI = 0.37–0.99; OR = 2.16, 95% CI = 1.36–3.42; OR = 1.94, 95% CI = 1.23–3.05, respectively). Both age and number of years since diagnosis were associated with obesity (OR = 1.04, 95% CI = 1.01–1.08; OR = 0.38; 95% CI = 0.20–0.72, respectively). The health behaviors of cervical cancer survivors did not differ from those of matched cancer-free controls. As health behaviors are modifiable, identification of cervical cancer survivors who are at risk of an unhealthy lifestyle would allow individual- and population-based intervention programs to more effectively use their limited resources. [ABSTRACT FROM AUTHOR]

Background: Ureteral reconstruction is required after surgical resection of the tumor invading the urinary tract in ovarian cancer with low incidence. There are no currently reported surgical outcomes of ureteral reconstruction during cytoreductive surgery. The aim of the study is to investigate the clinical features and surgical outcomes of ureteral reconstruction during primary, interval and secondary cytoreductive surgery for ovarian cancer.  METHODS: A total of 3226 patients who underwent primary, interval or secondary cytoreductive surgery for ovarian cancer between January 2000 and May 2021 were reviewed. Fifty-six patients who underwent ureteral reconstruction during cytoreductive surgery were included in the analysis.  RESULTS: Ureteral reconstruction was required in 1.7% (56/3226) of ovarian cancer patients. Of the 56 patients who underwent ureteral reconstruction during cytoreductive surgery, 35 (62.5%) had primary ovarian cancer, and 21 (37.5%) had recurrent ovarian cancer. The median tumor size invading the lower urinary tract was 2.0 cm (range, 0.4-9.5 cm). Ureteroneocystostomy with direct implantation (51.8%) and psoas hitch (8.9%), transureteroureterostomy (7.1%), and ureteroureterostomy (32.1%) were required as part of cytoreductive surgery. Complete cytoreduction with ureteral reconstruction was achieved in 83.9% (47/56) and the rest of the patient population (16.1%) achieved a gross residual tumor size of less than 1 cm. All complications, including hydronephrosis (33.9%), were managed, none resulting in long-term sequelae. In primary ovarian cancer, the 5-year disease-free survival and overall survival were 50.0% and 89.5%, respectively. In patients with recurrent ovarian cancer, the 5-year disease-free survival and overall survival were 23.6% and 64.0%, respectively.Conclusions: Ureteral reconstruction as a part of cytoreductive surgery for ovarian cancer could be performed with acceptable morbidities. Complete cytoreduction by a multidisciplinary surgical team, including urologic oncologists, should be pursued for the surgical management of ovarian cancer.Trial Registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objective: This study investigated site-specific differences in clinical factors for recurrence in patients who were newly diagnosed and treated for endometrial cancer. A model for predicting recurrence sites was generated.Methods: Electronic medical records' data were retrieved from January 2006 to December 2018 for patients who were diagnosed with endometrial cancer at the National cancer center in Korea. Recurrence sites were classified as local, regional, or distant. We used multinomial logistic regression models that modeled the log-odds for the three recurrence sites relative to non-recurrence as a linear combination of possible risk factors for the recurrence of endometrial cancer.Results: The data of 611 patients were selected for analysis; there were 20, 12, and 25 cases of local, regional, and distant recurrence, respectively, and 554 patients had no recurrence. High-grade disease was associated with local recurrence; non-endometrioid histology and parametrial invasion were risk factors for regional recurrence; additionally, parametrial invasion and no lymphadenectomy were associated with distant metastasis.Conclusion: We identified different risk factors specific for each type of recurrence site. Using these risk factors, we suggest that individually tailored adjuvant treatments be introduced for patients. [ABSTRACT FROM AUTHOR]

Objective: The prognosis of stage IVB cervical cancer is generally poor. In the current study, treatment outcomes were evaluated in patients with International Federation of Gynecologic Oncology stage IVB cervical cancer treated with radiotherapy and chemotherapy for progression-free survival (PFS) and treated-related toxicities. Study Design: The medical records of the patients with stage IVB cervical cancer who were treated at the National Cancer Center, South Korea were reviewed retrospectively. From February 2002 to February 2010, 45 patients were diagnosed with FIGO stage IVB cervical cancer. Survival and toxicities were compared between the 13 patients with concomitant chemoradiotherapy (CCRT) with weekly cisplatin versus 20 patients with CCRT with 5-fluorouracil/cisplatin. Results: Initial treatment included weekly cisplatin-CCRT, 5-fluorouracil/cisplatin-CCRT, neoadjuvant chemotherapy, and radiotherapy with subsequent combination chemotherapy in 13, 20, 4, and 5 patients, respectively. Overall survival (OS) and PFS were 26.2 and 6.7 months, respectively. There was no statistical difference in OS ( p = 0.47) and PFS ( p = 0.64) between the weekly cisplatin-CCRT and 5-fluorouracil/cisplatin-CCRT groups; however, the incidence of anemia >grade 3 as an acute toxicity was higher in the 5-fluorouracil/cisplatin-CCRT chemotherapy regimen group than the weekly cisplatin-CCRT group ( p = 0.03). Acute toxicity >grade 2 showed a tendency to be higher in the 5-fluorouracil/cisplatin-CCRT group. Based on multivariate analysis, poor performance status was the only independent prognostic factor of OS ( p = 0.03, 9.77; 95% CI 1.3-73.3) and PFS ( p = 0.04, 9.58; 95% CI 1.14-81.26). Conclusions: CCRT using combination chemotherapeutic agents may not have survival advantage over single agent cisplatin-based CCRT. Further improvement in treatment is needed to increase survival outcomes and to decrease treatment-related toxicities in patients with stage IVB cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine the ideal cut-off of nadir serum CA-125 level for prediction of progression free survival. Methods: Among 267 patients who achieved complete remission after chemotherapy, the correlation between nadir CA-125 and progression free survival were compared among the subgroups classified according to the distribution of CA-125. The diagnostic odds ratio and area under the receiver operator characteristics curve were compared at various cut-off points. Results: The nadir CA-125 levels did not have prognostic value under 12 U/mL (to 75 percentile). In contrast, they were significantly correlated with progression free survival only when the CA-125 level was greater than 12, which was 75 percentile (p=0.034). In predicting progression free survival <6 and 12 months, the cut-off value of 18 (90 percentile) showed superior diagnostic performance over 10 or 12 U/mL. Compared with patients who showed nadir levels between 0 and 12 U/mL (0 to 75 percentile), those with nadir >18 U/mL showed a hazard ratio of 2.85 (95% confidence interval, 1.70 to 4.76; p<0.001); patients with nadir levels between 18 and 12 U/mL showed a the hazard ratio of 1.68 (95% confidence interval, 1.11 to 2.56; p=0.015) compared with those whose nadir levels were under 12 U/mL. Conclusion: The predictive power of the traditional cut-off of 10 U/mL to classify a risk group or to identify high risk patients was unsatisfactory. The optimal diagnostic performance was observed at the cut-off of 18 U/mL and this can be proposed to dichotomize cut-off values to predict outcomes among individual patients. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine whether the inclusion of additional cycles of carboplatin-paclitaxel is beneficial to patients with high posttreatment serum CA-125 levels. Methods: Among patients who achieved remission after six cycles of carboplatin-paclitaxel chemotherapy, those with CA-125 of 10-35 U/ml at the time of remission were divided into two groups (group A: six cycles of standard chemotherapy vs. group B: two or more additional cycles) and were analyzed. Results: Among the 436 patients with advanced epithelial ovarian cancer, 154 patients (46.8%) had CA-125 of 10-35 U/ml at the time of remission. Fifty-six patients (36.4%) received two or more cycles after the first six cycles of chemotherapy (group B). The addition of two or more cycles of chemotherapy did not improve the progression-free survival (p = 0.660). There was no statistical difference in the rates of CA-125 falling to <10 U/ml between the two groups (p = 0.256). Moreover, the degree of CA-125 decrease after six cycles of chemotherapy was similar regardless of the additional cycles (p = 0.656). Conclusion: The addition of two or more cycles of standard chemotherapy based on posttreatment CA-125 levels was not beneficial. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Objective : This study aims to determine whether neoadjuvant chemotherapy (NAC) has survival benefit in selected patients with advanced epithelial ovarian cancer (EOC) who have high risk of suboptimal cytoreduction which is represented by high serum CA-125 level. Methods : We retrospectively reviewed records of 314 patients with EOC including 94 patients who received NAC. After stratification by preoperative CA-125 levels, the progression-free survival (PFS) was compared between the NAC group and the primary debulking surgery (PDS) group. Results : The NAC group had more FIGO stage IV disease (P <0.001) and higher CA-125 levels (P <0.001). Although suboptimal resection rate was higher in the PDS group (50% vs. 18%, P <0.001), however, NAC was not associated with increased PFS in multivariate Cox analysis (P =0.334). Nevertheless, after stratification according to CA-125 levels, NAC showed survival benefit in the subgroup with high CA-125 levels (>2000U/ml; HR 0.62, P =0.037). Conclusion : Our preliminary data suggests the possible interaction between CA-125 levels and survival benefit of NAC. The randomized trial data about NAC should be stratified by the reproducible and relevant criteria such as preoperative serum CA-125 level to elucidate true survival benefit of NAC in ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Objectives : The purpose of this study was to clarify the role of resection for suspicious thoracic metastasis in cervical cancer patients with thoracotomy or video-assisted thoracic surgery (VATS). Methods : A retrospective study was performed involving patients with primary and recurrent cervical cancer who underwent surgical resections for suspicious thoracic metastatic lesions at a single academic institution between January 2003 and February 2009. Results : Twenty-three pulmonary resections were performed on 21 patients via thoracotomies (n =10), VATS (n =11), and thoracotomies following VATS (n =2). All suspicious pulmonary lesions were completely resected in all 3 surgical groups. A total of 49 surgical procedures were performed, as follows: 25 wedge resections, 9 lobectomies, 12 mediastinal lymph node dissections, 1 segmentectomy, 1 diaphragmatic resection, and 1 pleurectomy. The pathologic evaluation revealed metastasis from cervical cancer, primary lung cancer, no pathologic abnormality, and tuberculosis in 14, 7, 2, and 1 of the surgical specimens, respectively; 1 patient had primary lung cancer and mediastinal lymph node metastasis from cervical cancer. Different pathologic diagnoses were rendered in 6 patients compared to the image-based diagnoses. After pulmonary metastasectomy, 2 patients died from the disease, 3 patients were alive with disease, and 16 patients were alive without disease, with a median follow-up of 16 months (range, 2–67 months). Conclusions : Resection of suspicious thoracic metastasis with thoracotomy or VATS permits accurate pathologic diagnosis and favorable curative resection in selected patients with cervical cancer. [Copyright &y& Elsevier]

The aim of this study was to determine the maximum tolerated dose (MTD) and therapeutic efficacy of a newly developed CKD-602 topoisomerase I inhibitor and cisplatin in patients with recurrent epithelial ovarian cancer. CKD-602 (0.30 mg/m2 daily for 5 days) and cisplatin (60 mg/m2 on day 5) were administered to patients every 3 weeks with dose adjustment of CKD-602 by 0.05 mg/m2 daily until the MTD was reached. Dose-limiting toxicity was defined as grade ≥ 3 neutropenia or thrombocytopenia for more than 4 days or accompanied by fever ≥ 38.5°C, infection, hemorrhage, or transfusion; grade ≥ 3 nonhematological toxicity except for alopecia, nausea, and vomiting. We enrolled 26 patients with recurrent epithelial ovarian cancer who had measurable disease (MD) estimated by computed tomography scan ( n= 12) and nonmeasurable disease (NMD) evaluated by serum CA-125 levels ( n= 14). All patients received 188 cycles of CKD-602 and cisplatin with a median number of six cycles per patient (range, 2 to 12). MTD of CKD-602 was 0.30 mg/m2 daily. The overall response rate was 69.2% (18/26) with 58.3% (7/12) and 78.6% (11/14) in MD and NMD, respectively. Among the responsive patients, 14 were platinum sensitive (14/18, 77.7%) and four were platinum resistant (4/8, 50.0%). The most common toxicity was grade ≥ 3 neutropenia developing in 17 patients (65.4%) and 72 cycles (38.3%). Grade 3 nausea and anorexia were the most common gastrointestinal toxicities, developing in 15 cycles (8.0%) of four patients (15.4%) and 10 cycles (5.3%) of five patients (19.3%), respectively. The median disease-free interval was 6 months (range 0–26 months). CKD-602 at a concentration of 0.3 mg/m2 daily for 5 days and cisplatin at 60 mg/m2 on day 5 every 3 weeks showed high efficacy, with acceptable toxicity, against platinum-sensitive/resistant recurrent epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Single-nucleotide polymorphisms of the FAS −1377G/A, FAS −670A/G, and FASL −844T/C genes may alter transcriptional activity of these genes. Recent evidence suggests an association of these polymorphisms with an increased risk of cervical cancer, so we explored this relationship. Genotypes of 155 patients with cervical cancer and 160 healthy control subjects were determined using polymerase chain reaction–based restriction fragment length polymorphism (PCR-RFLP). Associations with cancer risk were estimated using two-sided logistic regression. We observed a significantly increased risk of lymph node metastasis associated with the FAS −1377 GA or AA polymorphism [odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.10 to 15.74; P = 0.036]. In addition, the FAS −670AG or GG genotype showed an increased incidence of node metastasis, but these findings were not statistically significant (OR = 3.67, 95% CI = 0.96–14.00, P = 0.059). There was no significant association between an increased risk of cervical cancer and polymorphisms of the death pathway genes FAS and FASL. None of the polymorphisms were associated with risk of advanced stage or histologic subtype of cervical cancer. In conclusion, FAS −1377 G→A polymorphism may be associated with an increased risk of lymph node metastasis in Korean cervical cancer patients. [Copyright &y& Elsevier]

Abstract: Objective.: Although the incidence of cervical adenocarcinoma is increasing, few genetic and epigenetic changes in its progression have been described. We hypothesized that RASSF1A methylation and KRAS and BRAF mutations may play an important role in cervical adenocarcinoma. Methods. : Archival primary carcinoma tissues (n =258) in uterine cervix consisting cervical adenocarcinomas (n =115) and squamous cell carcinomas (n =143) were evaluated for activating mutations of BRAF and KRAS and promoter hypermethylation of RASSF1A using methylation specific PCR and specific sequence analysis. HPV E7 Type-specific PCR was used for HPV-16 and -18 status. Results.: KRAS mutations were found in 16 adenocarcinomas (13.9%), while BRAF mutations were found in 5 (4.3%). RASSF1A methylation was found in 27 adenocarcinomas (23.5%) and inversely correlated with KRAS and/or BRAF mutation (p =0.002) in cervical adenocarcinoma. In cervical squamous cell carcinomas, KRAS mutations were detected only in 1 (0.7%) cases and RASSF1A hypermethylation was detected in 2 (1.4%). The frequency of KRAS mutation and RASSF1A methylation were significantly different between adenocarcinomas (P <0.001) and squamous cell carcinomas (P <0.001). Neither KRAS mutation nor RASSF1A methylation were associated with HPV status. RASSF1A hypermethylation and KRAS mutations and BRAF mutations are inversely correlated and play an important role in the development of adenocarcinomas. Conclusions. : These results are suggesting that these two histological types of cervical cancer arise through different molecular pathways in tumor development. Different genetic/epigenetic alterations may explain the possible different therapeutic responsiveness between adenocarcinoma and squamous cell carcinoma of uterine cervix seen in clinic. [Copyright &y& Elsevier]

An "ovarian cancer cluster region" (OCCR) has been reported in both BRCA1 and BRCA2. However, the clinical significance of the OCCR of BRCA1/2 has not yet been investigated. The medical records of 991 patients with epithelial ovarian, primary peritoneal, and fallopian tube cancer who underwent genetic testing for BRCA1 and/or BRCA2 from January 1, 2006, to August 31, 2019, were retrospectively reviewed. Sanger and next-generation sequencing analyses were used to test the BRCA1 and BRCA2 mutation status. Progression-free survival (PFS) and overall survival (OS) were compared according to the mutation location (OCCR vs. non-OCCR region). Survival outcomes were determined using Kaplan–Meier survival analysis. A total of 162 patients had BRCA1 pathogenic variants (PVs), and 76 had BRCA2 PVs. Patients with BRCA1 PV that in the OCCR region showed shorter PFS than those with BRCA1 PV outside the OCCR (22.6 months vs. 27.6 months, P = 0.038). In the platinum-sensitive subgroup of BRCA1 , patients with BRCA1 PV in the OCCR region showed shorter PFS than those in the non-OCCR group (P = 0.0197). On the other hand, BRCA2 variants did not exhibit any particular trend (32.8 months vs. 27.9 months , P = 0.468). However, no significant differences were detected in OS between patients with BRCA1/2 PVs, regardless of the location of the variants. Patients with BRCA1 PV in the OCCR had shorter PFS than those outside the OCCR. This tendency was more pronounced in the platinum-sensitive subgroup. To our knowledge, this is the first study of BRCA1/2 mutations based on the OCCR. • The clinical impact of pathogenic variants in the ovarian cancer cluster region (OCCR) of BRCA1 and BRCA2 was assessed. • The patients with BRCA1 mutations in the OCCR had shorter progression-free survival than those outside the OCCR. • This tendency was increased in platinum-sensitive patients. [ABSTRACT FROM AUTHOR]

The aims of this study were to determine whether polymorphisms of the interleukin (IL)-10 promoter might be associated with an increased risk of cervical cancer, and further whether systemic IL-10 concentration might be influenced by the genotypes in Korean women. Peripheral blood samples from patients with invasive cervical cancer (ICC, n=144) and non-cancer controls (NCC, n=179) were used to detect three biallelic IL-10 promoter polymorphisms at −1082, −819, and −592 sites by polymerase chain reaction-restriction fragment length polymorphism assay using MnlI, MaeIII and RsaI, respectively. The IL-10 serum concentration was measured with enzyme-linked immunosorbent assay. We compared the distribution of genotypes in both groups, evaluated the serum IL-10 level according to the genotypes, and analyzed the association of these polymorphisms with the risk of cervical cancer. The genotype at the −1082 site exhibited only the *A homozygote, and only two haplotypes were found in Korean women, one being −1082*A/−819*T/−592*A (ATA) and the other −1082*A/−819*C/−592*C (ACC). No association was found for IL-10 promoter polymorphisms among the ICC patients in comparison with the NCC subjects. The risk of cervical cancer was not increased in either genotype and the IL-10 serum concentration was not influenced by the genotypes in either group. Polymorphisms of the IL-10 promoter do not appear to be associated with cervical cancer risk or systemic IL-10 production in Korean women. [Copyright &y& Elsevier]

Backgrounds: We aimed to evaluate the prognosis in patients with synchronous endometrial and ovarian cancer (SEOC) by comparing the differences between double primary cancer (DPC) and metastatic cancer (MC).Methods: The medical records of 47 patients diagnosed synchronously with endometrial and ovarian cancer between January 2006 and December 2018 were retrospectively reviewed. Twenty-eight and 19 patients were diagnosed with DPC and MC, respectively. Demographics, recurrence-free survival (RFS), and 5-year overall survival (OS) were compared. The clinical factors affecting survival were evaluated using univariate and multivariate analyses.Results: The demographics were not different between both groups. Endometrioid histology and the International Federation of Gynecology and Obstetrics grade were higher in the MC group than in the DPC group (42.1% vs. 10.7%; P = 0.018, P = 0.002, respectively). The ratio of post-operative adjuvant therapy was not different in both groups. Recurrence occurred in five patients with DPC and seven with MC. The difference in RFS was not significantly different (P = 0.131) but the OS was different between both groups (P = 0.020). Histology and para-aortic lymph node metastasis were associated wtih RFS in univariate analysis, but no difference was found in multivariate analysis.Conclusions: Although DPC patients had longer OS, multivariate analysis did not identify any influential factors. Focus should be placed on defining the appropriate adjuvant treatment for high-risk patients, which will improve prognosis, rather than on discriminating between DPC and MC. [ABSTRACT FROM AUTHOR]

Background: Survival outcomes for patients with recurrent or advanced cervical cancer are poor. Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall response rate of 14·3%. GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer. We aimed to investigate whether a combination of GX-188E therapeutic DNA vaccine plus pembrolizumab showed antitumour activity against recurrent or advanced cervical cancer.Methods: In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced, inoperable cervical cancer, who were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically confirmed recurrent or advanced HPV-positive (HPV-16 or HPV-18) cervical cancer, and who had progressed after available standard-of-care therapy were recruited from seven hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, and 19, with one optional dose at week 46 that was at the investigator's discretion, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the overall response rate within 24 weeks assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 in patients who received at least 45 days of treatment 45 days of treatment with at least one post-baseline tumour assessment, and this is the report of a planned interim analysis. This trial is registered with ClinicalTrials.gov, NCT03444376.Findings: Between June 19, 2018, and March 20, 2020, 36 patients were enrolled and received at least one dose of the study treatment. 26 patients were evaluable for interim activity assessment, with at least one post-baseline tumour assessment at week 10. At the data cutoff date on March 30, 2020, median follow-up duration was 6·2 months (IQR 3·5-8·1). At 24 weeks, 11 (42%; 95% CI 23-63) of 26 patients achieved an overall response; four (15%) had a complete response and seven (27%) had a partial response. 16 (44%) of 36 patients had treatment-related adverse events of any grade and four (11%) had grade 3-4 treatment-related adverse events. Grade 3 increased aspartate aminotransferase, syncope, pericardial effusion, and hyperkalaemia, and grade 4 increased alanine aminotransferase were reported in one patient each. No treatment-related deaths were reported.Interpretation: Treatment with GX-188E therapeutic vaccine plus pembrolizumab for patients with recurrent or advanced cervical cancer was safe and treatment-related adverse events were manageable. This combination therapy showed preliminary antitumour activity in this interim analysis, which could represent a new potential treatment option for this patient population. This trial is ongoing.Funding: National OncoVenture. [ABSTRACT FROM AUTHOR]

Embryonic-natural orifice transumbilical endoscopic surgery is currently used for adnexectomy or hysterectomy. Embryonic-natural orifice transumbilical endoscopic surgery for myomectomy with traction of two directional sutures in a 32-year-old woman enabled the minimal surgical approach for myomectomy and efficient and safe morcellation and retrieving of myoma. This novel surgical approach could be used as part of minimal surgery in the surgical management of myoma. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the incidence of colon cancer as a second primary cancer (CCSPC) and the survival outcomes of women with and without CCSPC after the diagnosis of endometrial cancer (EC).Methods: The standardized incidence ratio (SIR) of CCSPC and survival outcomes of EC survivors with and without CCSPC were analyzed using data from January 1 1993 to December 31 2011, obtained from the Korea Central Cancer Registry.Results: Of 14,797 EC survivors, 147 (0.99%) developed CCSPC after an average interval of 5.5 years. The SIR of CCSPC among EC survivors was 2.56, higher than that of colon cancer in the general population. The SIR of CCSPC was highest for the ascending (3.77), followed by the transverse (3.45), descending colon (2.06), and rectum (1.99). The risk of a proximal site of CCSPC was high, especially within 5 years after the diagnosis of EC in the ascending (SIR, 4.37) and transverse (4.91) colon, and in young survivors (< 60 years) in the ascending (5.19) and transverse (3.82) colon. The 5- and 10-year overall survival rates were 84.8 and 80.4% among survivors with EC only and 89.2 and 76.3% for survivors with CCSPC, respectively.Conclusions: The risk of CCSPC among EC survivors increases especially in the proximal colon in young survivors. These results could be used for surveillance and counseling of EC survivors. [ABSTRACT FROM AUTHOR]

Background Human papillomavirus (HPV) testing based on cervical samples is important for use in cervical cancer screening. However, cervical sampling is invasive. Therefore, non-invasive methods for detecting HPV, such as urine samples, are needed. Objectives For HPV detection in urine samples, two real-time PCR (RQ-PCR) tests, Roche cobas 4800 test (Roche_HPV; Roche Molecular Diagnostics) and Abbott RealTime High Risk HPV test (Abbott_HPV; Abbott Laboratories) were compared to standard cervical samples. Study design The performance of Roche_HPV and Abbott_HPV for HPV detection was evaluated at the National Cancer Center using 100 paired cervical and urine samples. The tests were also compared using urine samples stored at various temperatures and for a range of durations. Results The overall agreement between the Roche_HPV and Abbott_HPV tests using urine samples for any hrHPV type was substantial (86.0% with a kappa value of 0.7173), and that for HPV 16/18 was nearly perfect (99.0% with a kappa value of 0.9668). The relative sensitivities (based on cervical samples) for HPV 16/18 detection using Roche_HPV and Abbott_HPV with urine samples were 79.2% (95% CI; 57.9–92.9%) and 81.8% (95% CI; 59.7–94.8%), respectively. When the cut-off C T value for Abbott_HPV was extended to 40 for urine samples, the relative sensitivity of Abbott_HPV increased to 91.7% from 81.8% for HPV16/18 detection and to 87.0% from 68.5% for other hrHPV detection. The specificity was not affected by the change in the C T threshold. Conclusions Roche_HPV and Abbott_HPV showed high concordance. However, HPV DNA detection using urine samples was inferior to HPV DNA detection using cervical samples. Interestingly, when the cut-off C T value was set to 40, Abbott_HPV using urine samples showed high sensitivity and specificity, comparable to those obtained using cervical samples. Fully automated DNA extraction and detection systems, such as Roche_HPV and Abbott_HPV, could reduce the variability in HPV detection and accelerate the standardization of HPV detection in urine. Thus, urine samples may be an effective alternative for HPV detection in women who hesitate to participate in cervical cancer screening programs. [ABSTRACT FROM AUTHOR]

Purpose To analyze the toxicities and dose–volume histogram parameters of external-beam and magnetic resonance imaging–based intracavitary brachytherapy in cervical cancer patients. Methods and Materials Acute and late toxicities were assessed in 135 patients divided into four groups: group 1, grade 0; group 2, grades 1–4; group 3, grades 0–1; and group 4, grades 2–4. The doses at the International Commission on Radiation Units and Measurements (D ICRU ) and minimum doses to the most exposed 0.1, 1, 2, and 5 cc (D 0.1cc , D 1cc , D 2cc , and D 5cc ) of normal organs were calculated as equivalent doses in 2 Gy (α/β = 3). Results The median follow-up was 35.2 months. For rectum, D ICRU , D 0.1cc , D 1cc , and D 2cc were significantly different between groups 1 and 2 and D ICRU , D 0.1cc , and D 1cc between groups 3 and 4. For bladder, D 0.1cc , D 1cc , and D 2cc were significantly different between groups 1 and 2 and D ICRU , D 1cc , D 2cc , and D 5cc between groups 3 and 4. Grade 2–4 bladder toxicity occurred in fewer patients with D 2cc ≤ 95 Gy than those with D 2cc > 95 Gy (7% vs. 22%, p = 0.014). Conclusions D ICRU , D 0.1cc , D 1cc , and D 2cc are relevant for predicting late rectal toxicities. The patients with bladder D 2cc > 95 Gy are required to be in close observation for severe late toxicities. [ABSTRACT FROM AUTHOR]

Background and purpose The efficacy of prophylactic extended-field irradiation (EFI) plus concomitant cisplatin in patients with locally advanced uterine cervical cancer (LAUCC) is unknown, nor is it known whether tumor carbonic anhydrase IX (CA9) expression level, a hypoxia marker, influences survival outcome. Material and methods We recruited patients with UCC, FIGO stage IB1 with pelvic lymph node (LN) metastases to IVA with negative para-aortic LN on PET/CT. CA9 expression was examined and patients were randomized to either EFI or pelvic only radiotherapy (PRT) in each CA9 group. The primary outcomes were para-aortic recurrence-free survival (PARFS) and disease-free survival (DFS). Results Between 2006 and 2011, 79 patients with CA9-positive and 37 with CA9-negative tumors were enrolled, respectively. The median follow-up period was 69.2 months (range 6.8–102.1). For CA9-positive patients, 5-year PARFS was 100% and 81.7% for those receiving EFI and PRT ( p = 0.007), respectively. DFS was 78.6% for EFI and 71.3% for PRT patients ( p = 0.353). For CA9-negative patients, 5y PARFS was 100% and 94.1% for EFI and PRT ( p = 0.317), respectively. DFS was 100% for EFI and 70.7% for PRT ( p = 0.018). Conclusion EFI significantly reduced recurrences in PAN in patients with CA9-positive tumors, but survival outcome was not improved, due to high local recurrence and high distant metastases rates. This study indicates the necessity for new therapeutic strategies for LAUCC patients whose tumors show high CA9 expression. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to identify the uptake rate of risk-reducing salpingo-oophorectomy (RRSO) and the factors affecting this rate among female BRCA1 or BRCA2 mutation carriers at the National Cancer Center of Korea. Methods: Between April 2007 and December 2014, 450 women underwent BRCA gene testing, and 97 women were found to have BRCA1/2 mutations. Through the review of medical records, 42 candidates for RRSO were identified. Of these, 22 underwent RRSO. Demographic, clinical, and consultation-related factors were compared between the RRSO and non-RRSO groups. Results: The uptake rate of RRSO was 52.4 %. The mean time interval between genetic testing and surgery in the RRSO group was 7.3 months (range 0.6-33.9). The prevalence of amenorrhea was greater in the RRSO group than in the non-RRSO group (59.1 % vs. 20.0 %; P = 0.010). More women in the RRSO group were consulted with gynecologic oncologists (95.5 % vs. 60.0 %; P = 0.008). In multivariate analyses, amenorrhea at the time of genetic counseling (OR 16.44; 95 % CI 1.16-232.82; P = 0.038) and consultation with gynecologic oncologists (OR 30.78; 95 % CI 1.34-707.21; P = 0.032) were identified as factors affecting the carrier's decision to undergo RRSO. One patient in the non-RRSO group (5.0 %) developed primary peritoneal carcinoma, which was diagnosed 4.6 years after genetic testing. Conclusions: The uptake rate of RRSO among BRCA1/2 mutation carriers was affected by the presence of amenorrhea and consultation with gynecologic oncologists. Gynecologic oncologists with clinical experience with ovarian cancer should play a major role in aiding carriers' decision-making concerning RRSO. [ABSTRACT FROM AUTHOR]

Objectives Our objective was to assess the effects of chemoradiotherapy with paclitaxel and carboplatin on activity including local and distant control, and acute and late toxicity as adjuvant therapy after primary surgery in patients with cervical cancer. Methods Twenty-eight patients with FIGO stage IBI-IIB cervical cancer who received adjuvant concurrent chemoradiotherapy with paclitaxel and carboplatin from February 2000 to November 2001 were analyzed in this study. Adjuvant chemoradiotherapy was done if there were more than 1 positive finding as following criteria; more than 1 positive lymph node, full-thickness involovement of cervix, and positive resection margin. The stages of the patients were IB1 in 18 patients, IB2 in 2 patients, IIA in 4 patients, and IIB in 4 patients. Medical records were reviewed retrospectively. Paclitaxel 135 mg/m2, followed by carboplatin with AUC of 4.5 mg/ml/min were administered intravaenously with an interval of at least 4 weeks. The toxicity of the treatment was evaluated and graded by WHO criteria. Results Granulocytopenia was the most common toxicity and grade III or IV granulocytopenia were observed in 7 patients (25.0%). Neurotoxicity of grade 1 and 2 was observed in 6 patients (21.4%). None of the patients had a progressive or recurrent disease during the follow-up period ranged from 6 to 33 months (median: 12.5 months). Conclusions The adjuvant chemoradiotherapy with paclitaxel and carboplatin seems to be effective and well-tolerated for the treatment of high risk group of cervical cancer after surgical therapy. A further study with large number of cases and longer duration of follow-up needed to support this study. [ABSTRACT FROM AUTHOR]

Objective To evaluate the impact of lower limb lymphedema (LLL) on quality of life (QOL) in cervical, ovarian, and endometrial cancer survivors after pelvic lymph node dissection. Study design A cross-sectional case-control study was performed using the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). In total, 25 women with LLL and 28 women without LLL completed both questionnaires. Results The GCLQ-K total symptom score and scores for swelling-general, swelling-limb, and heaviness were significantly higher in the LLL group than in the control group. In the EORTC QLQ-C30, the LLL group reported more financial difficulties compared to the control group (mean score, 16.0 vs. 6.0; P = 0.035). Global health status was poorer in the LLL group with borderline statistical significance (mean score, 62.7 vs. 71.4; P = 0.069). Spearman's correlations suggested that global health status in the EORTC QLQ-C30 correlated with the GCLQ-K total symptom score (in the LLL group, R = −0.64, P = 0.001; in the control group, R = −0.42, P = 0.027). Conclusions QOL decreases due to LLL-related symptoms and financial difficulty in women with LLL. Well-designed prospective studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

-Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the surgical outcome of a subcutaneous negative pressure drain without subcutaneous suture on wound healing in women undergoing abdominal gynecologic surgery. Study design: The medical records of total 322 patients who underwent abdominal surgery, including cytoreductive surgery for ovarian cancer, between March 2010 and January 2013 were reviewed retrospectively. Patients were divided into two groups by the presence of subcutaneous negative pressure drains without subcutaneous suture, or suture without drainage. Results: Patient's characteristics in the two groups were not statistically different. Among all patients, the 71 patients who had a subcutaneous wound drain achieved a higher rate of clear healing (97.2% vs. 88.8%; p =0.033): 100% vs. 98.0% (not significant) in 126 benign and 95.6% vs. 82.8% (p =0.032) in 196 malignant disease patients. In a multivariate analysis, wound drain placement was an independent prognostic factor affecting the surgical wound outcome; the disruption (OR, 0.100; 95% CI, 0.021–0.485; p =0.004) rate was significantly lower with subcutaneous negative pressure drain. Placement of a subcutaneous negative pressure drain without subcutaneous suture resulted in clinical benefit, such as shorter admission duration (median, 8 vs. 11 days; p =0.021). Conclusions: Application of subcutaneous negative pressure drain is one of the effective and easy ways for clearer wound healing after major gynecologic surgery for malignant disease. [Copyright &y& Elsevier]

Abstract: Background and purpose: Lymph node (LN) metastasis is a well-known prognostic factor of the cervical cancer. In the current study, the size of metastatic LN was evaluated for its significance in the patients treated with definitive radiotherapy. Materials and methods: LN metastasis was evaluated for the 268 consecutive patients. The short-axis diameters of the largest LN were measured on magnetic resonance images for the 155 patients with LN metastasis. All the patients were classified into three groups: the negative lymphadenopathy (group N), the small (<15mm) lymphadenopathy (group SP), and the large (⩾15mm) lymphadenopathy (group LP). Results: Patients in the group LP showed significantly lower survival rates than the groups N and SP (5-year overall survival rates of 89%, 82%, and 58%, for groups N, SP, and LP, respectively, P <0.001; 5-year disease-free survival rates of 80%, 67%, and 50%, respectively, P <0.001). Regarding the pattern of failure, patients in the group LP showed inferior regional control rates and higher distant metastasis. Conclusion: The current study shows that the patients with large metastatic LNs are at increased risk of dying from early distant metastasis with substantial number of combined regional failures. Adoption of more effective systemic treatment as well as high radiotherapy dose for LNs may improve cure rates for these patients. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and toxicity of combined paclitaxel and carboplatin treatment for persistent or recurrent uterine sarcoma. Methods: Paclitaxel was administrated at 175 mg/m intravenously over 3 h plus carboplatin at AUC 5 intravenously over 30 min every 3-week cycle in patients with recurrent or progressive uterine sarcoma, who were unsuitable candidates for curative treatment with either surgery or radiotherapy. The Simon's two-stage optimal design was chosen for defining the total number of patients required for the phase II study. A total of 13 patients were entered in the study at the first stage of trial. A median of four cycles were administrated per patient, with a range of one to nine cycles. Prior to the study, 4 (30.8 %) of the 13 patients had received radiotherapy or chemotherapy. The response was measured by evaluation of the size of the mass by CT scan. Results: The overall response rate was 15.4 % (2/13), with two patients exhibiting partial responses. There was 1 (7.7 %) case of stable disease and 9 (69.2 %) cases of progression disease. The median progression free survival was 2.23 months (95 % confidence interval 1.94-3.67). Peripheral neuropathy and hematologic toxicity, including anemia and neutropenia, were the most frequent adverse events. One patient died from treatment-related toxicities. Conclusions: Paclitaxel in combination with carboplatin demonstrated acceptable levels of toxicity, but it was not active in the treatment of recurrent or progressive uterine sarcoma. This regimen might have limited role for advanced uterine sarcomas. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The purpose of this study was to evaluate the intra- and postoperative urologic complications and management in patients with cervical or endometrial cancer treated with laparoscopic radical hysterectomy and lymphadenectomy. Methods: We retrospectively reviewed the medical records of 146 patients with cervical or endometrial cancer who underwent total laparoscopic radical hysterectomy with lymphadenectomy between August 2002 and April 2011. The intra- and postoperative urologic complications were analyzed. Results: Double ureteral stents were inserted prophylactically in 13 patients (8.9 %), 2 of whom had postoperative urologic complications. Nine patients (6.2 %) had postoperative urologic complications. Of four patients with ureterovaginal fistulas, two were treated conservatively with cystoscopic placement of ureteral stents and two underwent ureteroneocystostomies. Vesicovaginal fistulas occurred in two patients, both of whom underwent vesicovaginal fistula repairs. One patient noted to have a bladder injury intraoperatively had a laparoscopic repair, and one patient noted to have a ureteral injury postoperatively was treated conservatively with cystoscopic placement of ureteral stents. Conclusions: Iatrogenic lower urinary tract injuries during laparoscopic radical hysterectomy are relatively common complications. Intraoperative prophylactic ureteral stent insertion and the early detection of urologic complications postoperatively is advised for patients who undergo laparoscopic radical hysterectomies. [ABSTRACT FROM AUTHOR]

During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The validity of the sentinel lymph node (SLN) procedure for the assessment of nodal status in patients with endometrial cancer is unclear. We aimed to assess the diagnostic performance of this procedure. Methods: We searched the PubMed and Embase databases for studies published before June 1, 2011. Eligible studies had a sample size of at least 10 patients, and reported the detection rate and/or sensitivity of the SLN biopsy. Results: We identified 26 eligible studies, which included 1101 SLN procedures. The overall weighted-mean number of harvested SLNs was 2.6. The detection rate and the sensitivity were 78% (95% confidence interval [CI]=73%–84%) and 93% (95% CI=87%–100%), respectively. Significant between-study heterogeneity was observed in the analysis of the detection rate (I-squared statistic, 80%). The use of pericervical injection was correlated with the increase of the detection rate (P =0.031). The hysteroscopic injection technique was associated with the decrease of the detection rate (P =0.045) and the subserosal injection technique was associated with the decrease of the sensitivity (P =0.049), if they were not combined with other injection techniques. For the detection rate, significant small-study effects were noted (P <0.001). Conclusions: Although SLN biopsy has shown good diagnostic performance in endometrial cancer, such performance should be interpreted with caution because of significant small study effects. Current evidence is not yet sufficient to establish the true performance of SLN biopsy in endometrial cancer. [Copyright &y& Elsevier]

Abstract: Objective: The objective of this study was to describe the development and experience in resection of tumor at the porta hepatis in patients with ovarian cancer by an interdisciplinary team approach. Methods: From August 2007 to June 2009, 11 women (2 primary and 9 recurrent ovarian cancers) underwent extended cytoreductive surgery including resection of tumor at the porta hepatis by hepatobiliary surgeons. Results: Tumor resection at the porta hepatis was required in 7.1% of the patients (11/155) during the study period. The median tumor size of the porta hepatis was 2.0cm (range, 0.7–4cm). All visible tumors at the porta hepatis were completely resected with co-operation of hepatobiliary surgeons. Optimal cytoreduction was achieved in all patients. There was no significant morbidity related to tumor resection of the porta hepatis and mortality associated with surgery. Five of 11 patients had recurrent disease at median 8months (range, 1–13) after the surgery with a median follow-up of 8months (range, 3–21months). Conclusion: Tumor resection at the porta hepatis is feasible with acceptable morbidities in patients with ovarian cancer by an interdisciplinary team approach with hepatobiliary surgeons. Long term follow up is needed to know the impact on survival. [Copyright &y& Elsevier]

Purpose: To develop a prediction model to identify a low-risk group for distant recurrence in patients with locally advanced cervical cancer treated by concurrent chemoradiation. Methods and Materials: Prospectively, 62 patients with locally advanced cervical cancer were recruited as a training cohort. Clinical variables and parameters obtained from positron emission tomography (PET) and magnetic resonance imaging were analyzed by logistic regression. For the test set, 54 patients were recruited independently. To identify the low-risk group, negative likelihood ratio (LR) less than 0.2 was set to be a cutoff. Results: Among the training cohort, multivariate logistic analysis revealed that advanced International Federation of Gynecology and Obstetrics (FIGO) stage and a high serum squamous cancer cell (SCC) antigen level were significant risk factors (p = 0.015 and 0.025, respectively). Using the two parameters, criteria to determine a low-risk subset for distant recurrence were postulated: (1) FIGO Stage IIB or less and (2) pretreatment SCC < 2.4 (Model A). Positive pelvic node on PET completely predicted all cases with distant recurrence and thus was considered as another prediction model (Model B). In the test cohort, although Model A did not showed diagnostic performance, Model B completely predicted all cases with distant recurrence and showed a sensitivity of 100% with negative LR of 0. Across the training and test cohort (n = 116), the false negative rate was 0 (95% confidence interval 0%–7.6%). Conclusions: Positive pelvic node on PET is a useful marker in prediction of distant recurrence in patients with locally advanced cervical cancer who are treated with concurrent chemoradiation. [ABSTRACT FROM AUTHOR]