Effect of BRCA1/2 Mutational Status on Survival Outcomes According to Secondary Cytoreductive Surgery and Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer: A Real-World Evidence Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to investigate the impact of BRCA1/2 mutational status on survival outcomes in patients with platinum-sensitive relapsed (PSR) epithelial ovarian cancer (EOC). @*Materials and Methods@#We retrospectively identified patients who received secondary treatment for PSR EOC at our institution between January 2007 and June 2021 and who underwent BRCA1/2 gene testing by either germline or somatic methods. The association between BRCA1/2 mutational status and survival outcomes was evaluated. Both secondary cytoreductive surgery (CRS) and maintenance therapy were stratified considering real-world clinical practice. @*Results@#Of 262 patients, 91 (34.7%) and 171 (65.3%) were assigned to BRCA1/2 mutation and wild-type groups, respectively. The two groups had similar proportions of patients undergoing secondary CRS (26.4% vs. 32.7%, p=0.286) and maintenance therapy (54.9% vs. 46.2%, p=0.178). Overall, no differences in progression-free survival (PFS; median, 19.7 vs. 15.1 months, p=0.120) and overall survival (OS; p=0.400) were observed between the two groups. In multivariate analyses, BRCA1/2 mutational status was not associated with PFS (adjusted hazard ratio, 0.816; 95% confidence interval, 0.596 to 1.119; p=0.207). BRCA1/2 mutational status did not affect PFS among patients who underwent secondary CRS (n=80) and among those who did not (n=182) (p=0.074 and p=0.222, respectively). PFS did not differ in the BRCA1/2 mutational status among the patients who received bevacizumab maintenance (n=90, p=0.992). @*Conclusion@#In this real-world evidence study, BRCA1/2 mutational status itself was not associated with PFS and OS in PSR EOC, which was consistent with whether secondary CRS or not and with bevacizumab maintenance.

Image-Guided Versus Conventional Brachytherapy for Locally Advanced Cervical Cancer: Experience of Single Institution with the Same Practitioner and Time Period / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to compare treatment outcomes and toxicity profile between imaged-guided brachytherapy (IGBT) versus conventional brachytherapy (CBT) performed by the same practitioner during the same time period. @*Materials and Methods@#Medical records of 104 eligible patients who underwent brachytherapy for locally advanced cervical cancer were retrospectively reviewed. Fifty patients (48.1%) underwent IGBT, and 54 (51.9%) patients underwent CBT. All patients underwent concurrent chemoradiation with cisplatin. High-dose-rate intracavitary brachytherapy with dose prescription of 25-30 Gy in 4-6 fractions was performed for all patients. Late lower gastrointestinal (GI) and urinary toxicities occurred more than 3 months after the end of brachytherapy were included for comparative and dosimetric analyses. @*Results@#The median follow-up period was 18.33 months (range, 3.25 to 38.43 months). There were no differences in oncologic outcomes between the two groups. The IGBT group had lower rate of actuarial grade ≥ 3 toxicity than the CBT group (2-year, 4.5% vs. 25.7%; p=0.030). Cumulative equieffective D2cc of sigmoid colon was significantly correlated with grade ≥ 2 lower GI toxicity (p=0.033), while equieffective D2cc of rectum (p=0.055) and bladder (p=0.069) showed marginal significance with corresponding grade ≥ 2 toxicities in the IGBT group. Half of grade ≥ 3 lower GI toxicities impacted GI tract above the rectum. Optimal thresholds of cumulative D2cc of sigmoid colon and rectum were 69.7 Gy and 70.8 Gy, respectively, for grade ≥ 2 lower GI toxicity. @*Conclusion@#IGBT showed superior toxicity profile to CBT. Evaluating the dose to the GI tract above rectum by IGBT might prevent some toxicities.

The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.

Lymph Node Ratio Is a Strong Prognostic Factor in Patients with Early-Stage Cervical Cancer Undergoing Minimally Invasive Radical Hysterectomy

Purpose@#To determine whether the prognostic impact of lymph node ratio (LNR), defined as the ratio between the number of positive lymph nodes and removed lymph nodes, differs between open and minimally invasive surgical approaches for radical hysterectomy (RH) in node-positive, early-stage cervical cancer. @*Materials and Methods@#We retrospectively identified 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 patients who underwent primary type C RH between 2010 and 2018. Among them, only those with pathologically proven lymph node metastases who received adjuvant radiation therapy were included. The prognostic significance of LNR was investigated according to open surgery and minimally invasive surgery (MIS). @*Results@#In total, 55 patients were included. The median LNR (%) was 9.524 (range, 2.083–62.500). Based on receiver operating characteristic curve analysis, the cut-off value for LNR (%) was determined as 8.831. Overall, patients with high LNR (≥8.831%;n=29) showed worse disease-free survival (DFS) than those with low LNR (<8.831%, n=26) (p=0.027), whereas no difference in overall survival was observed. Multivariate analyses adjusting for clinicopathologic factors revealed that DFS was adversely affected by both MIS [adjusted hazard ratio (HR), 8.132; p=0.038] and high LNR (adjusted HR, 10.837; p=0.045). In a subgroup of open surgery cases, LNR was not associated with disease recurrence. However, in a subgroup of MIS cases, high LNR was identified as an independent poor prognostic factor for DFS (adjusted HR, 14.578; p=0.034). @*Conclusion@#In patients with node-positive, early-stage cervical cancer, high LNR was associated with a significantly higher disease recurrence rate. This relationship was further consolidated among patients who received MIS RH.

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

Thymoquinone (TQ) is a bioactive component derived from the seeds of Nigella sativa that are commonly as black cumin. Evidences indicate that the medicinal properties of TQ have been recognized for more than 2000 years. TQ has been shown to possess potent chemopreventive properties that include anti-inflammatory and anti-neoplastic activities. Recent studies have unraveled the multiple mechanisms through which TQ exerts its chemopreventive and anticancer activity in different cancer cells in a contextual manner. The present review aims to provide a brief compendium on the molecular mechanisms through which TQ inhibits signaling pathways underlying cancer genesis, progression, and metastasis.

Germline and Somatic BRCA1/2 Gene Mutational Status and Clinical Outcomes in Epithelial Peritoneal, Ovarian, and Fallopian Tube Cancer: Over a Decade of Experience in a Single Institution in Korea / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to present a single institutional experience with BRCA1/2 gene tests and the effects of pathogenic mutations in epithelial peritoneal, ovarian, and fallopian tube cancer (POFTC) on survival outcomes. @*Materials and Methods@#We identified patients with epithelial POFTCs who underwent BRCA1/2 gene testing by either germline or somatic methods between March 2007 and March 2020. Based on the BRCA1/2 test results, patients were divided into BRCA mutation and wild-type groups, followed by comparisons of clinicopathologic characteristics and survival outcomes after primary treatment. @*Results@#The annual number of POFTC patients who received BRCA1/2 gene tests increased gradually. In total, 511 patients were included and BRCA1/2 mutations were observed in 143 (28.0%). Among 57 patients who received both germline and somatic tests, three (5.3%) showed discordant results from the two tests. Overall, no differences in progression-free survival (PFS; p=0.467) and overall survival (p=0.641) were observed between the BRCA mutation and wild-type groups; however, multivariate analyses identified BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted hazard ratio [aHR], 0.765; 95% confidence interval [CI], 0.593 to 0.987; p=0.040). In 389 patients with International Federation of Gynecology and Obstetrics stage III-IV, different results were shown depending on primary treatment strategy: while BRCA1/2 mutation significantly improved PFS in the subgroup of neoadjuvant chemotherapy (aHR, 0.619; 95% CI, 0.385 to 0.995; p=0.048), it did not affect patient PFS in the subgroup of primary debulking surgery (aHR, 0.759; 95% CI, 0.530 to 1.089; p=0.135). @*Conclusion@#BRCA1/2 mutations are frequently observed in patients with epithelial POFTCs, and such patients showed better PFS than did those harboring wild-type BRCA1/2.

The power of the Risk of Ovarian Malignancy Algorithm considering menopausal status: a comparison with CA 125 and HE4 / 부인종양

OBJECTIVE: To identify the power of tumor markers for predicting ovarian cancer according to menopausal status. METHODS: The medical records of 876 women with ovarian cysts were retrospectively reviewed. Cancer antigen 125 (CA 125), human epididymis protein 4 (HE4), and Risk of Ovarian Malignancy Algorithm (ROMA) were analyzed. Sensitivity, specificity, and the receiver operating characteristic (ROC) curve analyses of these tumor markers were evaluated. RESULTS: The sensitivity of ROMA was 66.7% and the specificity was 86.8% to detect ovarian malignancy. The patients were divided into 2 groups according to menopausal status: premenopause (n=532, 60.7%) and postmenopause (n=344, 39.3%). For diagnostic accuracy, ROMA was lower than HE4 in premenopausal women (82.7% vs. 91.4%) and lower than CA 125 in postmenopausal women (86.9% vs. 88.7%). The ROC curve analysis revealed that the power of ROMA was not significantly better than that of HE4 in premenopausal women (area under the curve [AUC], 0.731 vs. 0.732, p=0.832), and it was also not significantly better than that of CA 125 in postmenopausal women (AUC, 0.871 vs. 0.888, p=0.440). CONCLUSION: The discrimination power of tumor markers for ovarian cancer was different according to menopausal status. In predicting ovarian malignancy, ROMA was neither superior to HE4 in premenopausal women nor superior to CA 125 in postmenopausal women.

Development of Web-Based Nomograms to Predict Treatment Response and Prognosis of Epithelial Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Discovery of models predicting the exact prognosis of epithelial ovarian cancer (EOC) is necessary as the first step of implementation of individualized treatment. This study aimed to develop nomograms predicting treatment response and prognosis in EOC. MATERIALS AND METHODS: We comprehensively reviewed medical records of 866 patients diagnosed with and treated for EOC at two tertiary institutional hospitals between 2007 and 2016. Patients’ clinico-pathologic characteristics, details of primary treatment, intra-operative surgical findings, and survival outcomes were collected. To construct predictive nomograms for platinum sensitivity, 3-year progression-free survival (PFS), and 5-year overall survival (OS), we performed stepwise variable selection by measuring the area under the receiver operating characteristic curve (AUC) with leave-one-out cross-validation. For model validation, 10-fold cross-validation was applied. RESULTS: The median length of observation was 42.4 months (interquartile range, 25.7 to 69.9 months), during which 441 patients (50.9%) experienced disease recurrence. The median value of PFS was 32.6 months and 3-year PFS rate was 47.8% while 5-year OS rate was 68.4%. The AUCs of the newly developed nomograms predicting platinum sensitivity, 3-year PFS, and 5-year OS were 0.758, 0.841, and 0.805, respectively. We also developed predictive nomograms confined to the patients who underwent primary debulking surgery. The AUCs for platinum sensitivity, 3-year PFS, and 5-year OS were 0.713, 0.839, and 0.803, respectively. CONCLUSION: We successfully developed nomograms predicting treatment response and prognosis of patients with EOC. These nomograms are expected to be useful in clinical practice and designing clinical trials.

Ovarian Cancer Prognostic Prediction Model Using RNA Sequencing Data

Ovarian cancer is one of the leading causes of cancer-related deaths in gynecological malignancies. Over 70% of ovarian cancer cases are high-grade serous ovarian cancers and have high death rates due to their resistance to chemotherapy. Despite advances in surgical and pharmaceutical therapies, overall survival rates are not good, and making an accurate prediction of the prognosis is not easy because of the highly heterogeneous nature of ovarian cancer. To improve the patient's prognosis through proper treatment, we present a prognostic prediction model by integrating high-dimensional RNA sequencing data with their clinical data through the following steps: gene filtration, pre-screening, gene marker selection, integrated study of selected gene markers and prediction model building. These steps of the prognostic prediction model can be applied to other types of cancer besides ovarian cancer.

Endometrial polyp surveillance in premenopausal breast cancer patients using tamoxifen

OBJECTIVE: To describe the endometrial pathologic lesions in premenopausal breast cancer patients with a history of tamoxifen (TMX) use. METHODS: We retrospectively reviewed the medical records of 120 premenopausal breast cancer patients with a history of TMX use that had undergone a gynecological examination. RESULTS: Among 120 patients, 44.2% (n=53) were asymptomatic with an endometrial thickness ≥5 mm, as assessed by transvaginal ultrasonography. Of the patients that reported abnormal uterine bleeding, 5% (n=6) had an endometrial thickness <5 mm and 20% (n=24) had an endometrial thickness ≥5 mm by transvaginal ultrasonography. The final group of patients were asymptomatic, but showed an abnormal endometrial lesion, such as an endometrial polyp, by transvaginal ultrasonography (30.8%, n=37). Of the 56 benign lesions that were histologically reviewed, 50 (41.7%) were endometrial polyps, 3 (2.5%) were submucosal myomas, 2 (1.7%) were endometrial hyperplasias, and 1 (0.8%) was chronic endometritis. There were 64 (53.3%) other non-pathologic conditions, including secreting, proliferative, and atrophic endometrium, or in some cases, there was insufficient material for diagnosis. In our data, only one case was reported as a complex hyperplasia without atypia arising from an endometrial polyp, and one patient was diagnosed with endometrioid adenocarcinoma. CONCLUSION: For premenopausal breast cancer patients with a history of TMX use, the majority of the patients were asymptomatic, and endometrial polyps were the most common endometrial pathology observed. Therefore, we believe that endometrial assessment before starting TMX treatment, and regular endometrial screening throughout TMX treatment, are reasonable suggestions for premenopausal breast cancer patients.

Elevated plasma fibrinogen levels and prognosis of epithelial ovarian cancer: a cohort study and meta-analysis / 부인종양

OBJECTIVE: To evaluate the effect of elevated plasma fibrinogen levels on the prognosis of epithelial ovarian cancer (EOC). METHODS: We reviewed the data of 217 patients with advanced-stage EOC between 2000 and 2012, and investigated the prognostic role of elevated plasma fibrinogen levels compared with serum CA-125 levels, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). For further evaluation, we performed a meta-analysis using 5 cohort studies published to July 2015, including our cohort study after a literature review. RESULTS: Among the four biomarkers, only plasma fibrinogen levels >485.2 mg/dL were correlated with impaired progression-free survival (PFS) and overall survival (OS) (median, 13.9 vs. 20.3 months and 42.2 vs. 55.4 months; p<0.010). Elevated plasma fibrinogen levels were an independent factor for poor PFS with marginal significance and OS (adjusted hazard ratios [HRs]=1.389 and 1.581; 95% confidence intervals [CIs]=0.979–1.972 and 1.032–2.423, respectively). Furthermore, crude and subgroup meta-analyses demonstrated that elevated plasma fibrinogen levels were associated with impaired PFS and OS in patients with all stage EOC. CONCLUSION: Elevated plasma fibrinogen levels be more important for predicting survival than serum CA-125 levels, NLR and PLR in patients with EOC, in particular, advanced-stage disease. Moreover, it may be related to poor prognosis of EOC.

Adipose Stromal Cells from Visceral and Subcutaneous Fat Facilitate Migration of Ovarian Cancer Cells via IL-6/JAK2/STAT3 Pathway / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Adipose stromal cells (ASCs) play an important regulatory role in cancer progression and metastasis by regulating systemic inflammation and tissue metabolism. This study examined whether visceral and subcutaneous ASCs (V- and S-ASCs) facilitate the growth and migration of ovarian cancer cells. MATERIALS AND METHODS: CD45– and CD31– double-negative ASCs were isolated from the subcutaneous and visceral fat using magnetic-activated cell sorting. Ovarian cancer cells were cultured in conditioned media (CM) obtained from ASCs to determine the cancer-promoting effects of ASCs. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, Boyden chamber assay, and western blotting were performed to determine the proliferative activity, migration ability, and activation of the JAK2/STAT3 pathway, respectively. RESULTS: CM from ASCs enhanced the migration of the ovarian cancer line, SKOV3, via activation of the JAK2/STAT3 signaling pathway. Interestingly, in response to ASC-CM, the ascites cells derived from an ovarian cancer patient showed an increase in growth and migration. The migration of ovarian cancer cells was suppressed by blocking the activation of JAK2 and STAT3 using a neutralizing antibody against interleukin 6, small molecular inhibitors (e.g., WP1066 and TG101348), and silencing of STAT3 using siRNA. Anatomical differences between S- and V-ASCs did not affect the growth and migration of the ovarian cancer cell line and ascites cells from the ovarian cancer patients. CONCLUSION: ASCs may regulate the progression of ovarian cancer, and possibly provide a potential target for anticancer therapy.

Prognostic factors in neuroendocrine cervical carcinoma

OBJECTIVE: To evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine cervical carcinoma (NECC). METHODS: The records of 61 patients with NECC diagnosed between 2000 and 2014 at Seoul National University Hospital and the National Cancer Center were retrospectively reviewed. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS: Of the 61 patients, 67.2% were diagnosed at early stage (I to IIA) with a median age of 49 years. Of those, 78% underwent surgery and 75.6% received postoperative adjuvant treatment. For patients diagnosed at advanced stage, 60.0% received chemotherapy only and 25.0% received concurrent chemoradiation therapy. In the univariate analysis, advanced stage (77 vs. 40 months, P=0.013), tumor size ≥2 cm (133 vs. 47 months, P=0.002) and mixed tumor (101 vs. 34 months, P=0.004) were shown to be poor prognostic factors. In the multivariate analysis, tumor stage, tumor size and tumor homology were shown to be independent prognostic factors for overall survival. Of the total, 39.3% of the patients experienced recurrence, and 54.1% of the patients had metastasis. Of the patients diagnosed at early stage, 51.2% experienced recurrence. CONCLUSION: Tumor stage, tumor size and tumor homology were found to be independent prognostic factors in patients with NECC. Even in patients diagnosed at early stage, recurrence and distant metastasis were frequently observed.

Systemic Inflammatory Response Markers and CA-125 Levels in Ovarian Clear Cell Carcinoma: A Two Center Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We compared the predictive and prognostic values of leukocyte differential counts, systemic inflammatory (SIR) markers and cancer antigen 125 (CA-125) levels, and identified the most useful marker in patients with ovarian clear cell carcinoma (OCCC). MATERIALS AND METHODS: The study included 109 patients with OCCC who did not have any inflammatory conditions except endometriosis, and underwent primary debulking surgery between 1997 and 2012. Leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet), SIR markers including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR), and CA-125 levels were estimated to select potential markers for clinical outcomes. RESULTS: Among potential markers (neutrophil, monocyte, platelet, NLR, MLR, PLR, and CA-125 levels) selected by stepwise comparison, CA-125 levels were best at predicting advanced stage disease, suboptimal debulking and platinum-resistance (cut-off values, > or = 46.5, > or = 11.45, and > or = 66.4 U/mL; accuracies, 69.4%, 78.7%, and 68.5%) while PLR > or = 205.4 predicted non-complete response (CR; accuracy, 71.6%) most accurately. Moreover, PLR < 205.4 was an independent factor for the reduced risk of non-CR (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.04 to 0.69), and NLR < 2.8 was a favorable factor for improved progression-free survival (PFS; adjusted hazard ratio, 0.49; 95% CI, 0.25 to 0.99) despite lack of a marker for overall survival among the potential markers. CONCLUSION: CA-125 levels may be the most useful marker for predicting advanced-stage disease. Suboptimal debulking and platinum-resistance, and PLR and NLR may be most effective to predict non-CR and PFS in patients with OCCC.

An Alternative Triage Strategy Based on Preoperative MRI for Avoiding Trimodality Therapy in Stage IB Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Adjuvant chemoradiation following primary surgery is frequently indicated in patients with stage IB cervical cancer. The aim of this study is to evaluate the role of a magnetic resonance imaging (MRI)-based strategy in avoiding trimodality therapy. MATERIALS AND METHODS: We retrospectively reviewed all patients with stage IB cervical cancer treated initially with primary surgery at Seoul National University Hospital. We suggest an alternative triage strategy in which the primary treatment modality is determined based on preoperative MRI findings. Using this strategy, primary surgery is only indicated when there is no evidence of parametrial involvement (PMI) and lymph node metastasis (LNM) in the MRI results; when there is evidence of either or both of these factors, primary chemoradiation is selected. Assuming that this strategy is applied to our cohort, we evaluate how the rate of trimodality therapy is affected. RESULTS: Of the 254 patients in our sample, 77 (30.3%) had at least one category 1 risk factor (PMI, LNM, positive resection margin) upon pathologic examination. If the MRI-based strategy had been applied to our cohort, 168 patients would have undergone primary surgery and 86 would have undergone primary chemoradiation. Only 25 patients (9.8%) would have required trimodality therapy based on an indication of at least one category 1 pathologic risk factor following radical hysterectomy. CONCLUSION: The inclusion of MRI in the decision-making process for primary treatment modality could have reduced the number of patients requiring trimodality therapy based on the indication of a category 1 risk factor from 30.3% to 9.8% in our cohort.

Prognostic value of preoperative intratumoral FDG uptake heterogeneity in early stage uterine cervical cancer / 부인종양

OBJECTIVE: We investigated the prognostic value of intratumoral [18F]fluorodeoxyglucose (FDG) uptake heterogeneity (IFH) derived from positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer. METHODS: Patients with uterine cervical cancer of the International Federation of Obstetrics and Gynecology (FIGO) stage IB to IIA were imaged with [18F]FDG PET/CT before radical surgery. PET/CT parameters such as maximum and average standardized uptake values (SUV(max) and SUV(avg)), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and IFH were assessed. Regression analyses were used to identify clinicopathological and imaging variables associated with progression-free survival (PFS). RESULTS: We retrospectively reviewed clinical data of 85 eligible patients. Median PFS was 32 months (range, 6 to 83 months), with recurrence observed in 14 patients (16.5%). IFH at an SUV of 2.0 was correlated with primary tumor size (p<0.001), SUV(tumor) (p<0.001), MTV(tumor) (p<0.001), TLG(tumor) (p<0.001), depth of cervical invasion (p<0.001), and negatively correlated with age (p=0.036). Tumor recurrence was significantly associated with TLG(tumor) (p<0.001), MTV(tumor) (p=0.001), SUV(LN) (p=0.004), IFH (p=0.005), SUV(tumor) (p=0.015), and FIGO stage (p=0.015). Multivariate analysis identified that IFH (p=0.028; hazard ratio, 756.997; 95% CI, 2.047 to 279,923.191) was the only independent risk factor for recurrence. The Kaplan-Meier survival graphs showed that PFS significantly differed in groups categorized based on IFH (p=0.013, log-rank test). CONCLUSION: Preoperative IFH was significantly associated with cervical cancer recurrence. [18F]FDG based heterogeneity may be a useful and potential predicator of patient recurrence before treatment.

Conventional versus nerve-sparing radical surgery for cervical cancer: a meta-analysis / 부인종양

OBJECTIVE: Although nerve-sparing radical surgery (NSRS) is an emerging technique for reducing surgery-related dysfunctions, its efficacy is controversial in patients with cervical cancer. Thus, we performed a meta-analysis to compare clinical outcomes, and urinary, anorectal, and sexual dysfunctions between conventional radical surgery (CRS) and NSRS. METHODS: After searching PubMed, Embase, and the Cochrane Library, two randomized controlled trials, seven prospective and eleven retrospective cohort studies were included with 2,253 patients from January 2000 to February 2014. We performed crude analyses and then conducted subgroup analyses according to study design, quality of study, surgical approach, radicality, and adjustment for potential confounding factors. RESULTS: Crude analyses showed decreases in blood loss, hospital stay, frequency of intraoperative complications, length of the resected vagina, duration of postoperative catheterization (DPC), urinary frequency, and abnormal sensation in NSRS, whereas there were no significant differences in other clinical parameters and dysfunctions between CRS and NSRS. In subgroup analyses, operative time was longer (standardized difference in means, 0.948; 95% confidence interval [CI], 0.642 to 1.253), while intraoperative complications were less common (odds ratio, 0.147; 95% CI, 0.035 to 0.621) in NSRS. Furthermore, subgroup analyses showed that DPC was shorter, urinary incontinence or frequency, and constipation were less frequent in NSRS without adverse effects on survival and sexual functions. CONCLUSION: NSRS may not affect prognosis and sexual dysfunctions in patients with cervical cancer, whereas it may decrease intraoperative complications, and urinary and anorectal dysfunctions despite long operative time and short length of the resected vagina when compared with CRS.

Clinicopathological aspects of patients with recurrence of borderline ovarian tumors

OBJECTIVE: Despite the good prognosis of borderline ovarian tumors (BOTs), a few BOT patients experience the relapse of disease, either borderline or malignant. However, the risk of recurrence of BOTs is somewhat controversial. We intended to find out the specific characteristics and prognosis of the recurrence of BOTs. METHODS: Between 1995 and 2012, 130 women were diagnosed with BOTs at a single institution. Eleven patients diagnosed and treated for the recurrence of BOTs including seven cancerous and four borderline relapses were included for the analysis in this retrospective study. Clinicopathological characteristics and surgical procedures as well as follow-up data with overall survival were assessed. Statistical analyses was performed using the chi2 test, t-test and log-rank test with Cox regression. RESULTS: One hundred and thirty patients with mean follow-up of 65.8 months were evaluated, of whom half were below 40 years old at their first diagnosis of BOTs. Among 11 recurrent cases (8.5%), 7 cancerous transformations (5.4%) and 4 borderline recurrences (3.1%) were detected with median time of 6 and 71 months after the primary surgery, respectively. Nine out of 11 recurrences were happened at their equal or below 40-years-old age at the primary diagnosis (P=0.027). Also, all 7 cancerous relapses arose from premenopausal women of median age of 35 years old. Twenty (15%) patients had laparoscopic surgery and they were all treated conservatively. Among those 20, 5 were suffered from relapse of BOTs and laparoscopic approach was proved to be a significant risk factor for disease relapse in our study (P=0.013). Although laparoscopic surgery was revealed had meaningful influence on disease free survival (P=0.024), it was not significant on overall survival (P=0.226). CONCLUSION: Laparoscopic conservative surgery for BOTs can be accepted under close follow-ups. And younger patients should be followed for long period to evaluate recurrence.

Characteristics of hereditary nonpolyposis colorectal cancer patients with double primary cancers in endometrium and colorectum

OBJECTIVE: The hereditary nonpolyposis colorectal cancer is inherited syndrome characterized by the development of cancers in various organ system; these includes colorectum, endometrium, and less frequently, small bowel, stomach, urinary tract, ovaries, and brain. We aimed to investigate the clinicopathologic characteristics of hereditary nonpolyposis colorectal cancer patients who had both endometrial and colorectal cancers. METHODS: Between January 2004 and December 2013, 12 women diagnosed with endometrial and colorectal cancers in a single institution were included in this analysis. For these patients, clinical and molecular findings were analyzed retrospectively. RESULTS: All 12 women undertook microsatellite instability analysis, and 9 (75%) were confirmed of having microsatellite instability-high. Among 9 cases with immunohistochemical staining for MLH1 and MSH2, 6 were positive for the loss of mismatch repair protein. Mutational analyses for MLH1 and MSH2 were performed in 3 out of 12 patients; all of them showed germline mutation. CONCLUSION: This study suggests that there is a genetic background in patients with double primary malignancies in their endometrium and colorectum when analyzed with microsatellite instability studies, immunohistochemistry staining, and mutation studies. This finding supports the necessity of re-defining the high-risk groups in endometrial cancers clinically. This will also help diagnose malignancies in such patients in early stages, as well as counsel other family members.

Outcome analysis in patients with uterine sarcoma

PURPOSE: To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. MATERIALS AND METHODS: We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). RESULTS: The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. CONCLUSION: The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.