Postoperative Adjuvant Chemoradiotherapy Versus Chemotherapy Alone for Stage III Endometrial Cancer: A Multicenter Retrospective Study.

INTRODUCTION: We aimed to evaluate the efficacy and toxicity of the combination of 6 cycles of chemotherapy and radiation therapy compared with chemotherapy alone as postoperative adjuvant therapy for patients with stage III endometrial cancer. METHODS: This retrospective cohort study included patients with stage III endometrial cancer who received postoperative chemoradiotherapy or chemotherapy alone at 6 hospitals between January 2009 and December 2019. The progression-free survival (PFS) and overall survival (OS) for each treatment group were analyzed using the Kaplan-Meier method. We also assessed differences in toxicity profiles between the treatment groups. RESULTS: A total of 133 patients met the inclusion criteria. Of these, 80 patients (60.2%) received adjuvant chemoradiotherapy and 53 (39.8%) received chemotherapy alone. The PFS and OS did not differ significantly between the groups. For patients with stage IIIC endometrioid subtype, the chemoradiotherapy group had significantly longer PFS rate than did the chemotherapy alone group (log-rank test, P = .019), although there was no significant difference in the OS (log-rank test, P = .100). CRT was identified as a favorable prognostic factor for PFS in multivariate analysis (adjusted HR, .37; 95% CI, .16-.87; P = .022). Patients treated with chemoradiotherapy more frequently suffered from grade 4 neutropenia (73.8% vs 52.8%; P = .018) and grade 3 or worse thrombocytopenia (36.3% vs 9.4%; P = .001) compared with the chemotherapy alone group. There were no differences between the 2 treatment groups in the frequency of toxicity-related treatment discontinuation or dose reduction. CONCLUSION: We confirmed that chemoradiotherapy yields longer progression-free survival than does chemotherapy alone for patients with stage IIIC endometrioid endometrial cancer, with an acceptable toxicity profile.

Secondhand smoke exposure, diabetes, and high BMI are risk factors for uterine cervical cancer: a cross-sectional study from the Korea national health and nutrition examination survey (2010-2018).

BACKGROUND: Human papilloma virus infection and tobacco smoking are the major risk factors for cervical cancer. There are limited studies searching other risk factors for cervical cancer and the results are not consistent. This study investigated the relations between cervical cancer and possible risk factors, including secondhand cigarette smoke exposure, diabetes, body mass index (BMI), and work schedule. METHODS: In this cross-sectional study, 29,557 women completed a cervical cancer questionnaire and were selected using 2010-2018 data from the Korea National Health and Nutrition Examination Survey. Details in secondhand smoke exposure, diabetes, BMI, and work schedule were assessed with participants' health interviews and health-related surveys. RESULTS: Two hundred sixty-two women (0.89%) in the sample were diagnosed with cervical cancer. Domestic secondhand smoke exposure, diabetes, and high BMI significantly increased cervical cancer risk. Respective odds ratios and 95% confidence intervals were: 1.547 (1.042-2.297), 2.156 (1.535-3.027), and 1.036 (1.006-1.067). Weekly work hours, and work schedule were not significantly related to cervical cancer incidence. CONCLUSION: Among Korean women, passive exposure to cigarette smoke at home, diabetes, and high BMI increase risk for cervical cancer.

Survival rates of patients who undergo minimally invasive surgery for endometrial cancer with cervical involvement.

Objective: Compare the oncologic outcomes of patients with intermediate-risk endometrial cancer who were staged by minimally invasive surgery with the outcomes of patients who underwent open surgery. Methods: Data from 206 patients with intermediate-risk endometrial cancer who were treated between January 2009 and January 2019 were reviewed. The patients' data were retrieved from five institutions. The patients were divided into two groups: those who underwent open surgery and those who underwent minimally invasive surgery. Tumor characteristics, recurrence rate, disease-free survival, and overall survival were compared according to surgical approach. Results: Among the 206 patients included in this study, 76 underwent open surgery (36.9%) and 130 underwent MIS (63.1%). In patients with stage IB endometrial cancer, the recurrence rate, disease-free survival, and overall survival were not significantly different between those who underwent minimally invasive surgery and those who underwent open surgery. However, in patients with stage II endometrial cancer, the recurrence rate was significantly higher among those who underwent minimally invasive surgery (37.5% vs. 5.3%, p = 0.013). Patients with stage II endometrial cancer who underwent minimally invasive surgery had a significantly lower disease-free survival (p = 0.012) than those who underwent open surgery, however, the overall survival (p = 0.252) was similar between the two groups. Conclusion: Minimally invasive surgery results in less favorable survival outcomes than open surgery in patients with stage II endometrial cancer.

Prediction of lymphovascular space invasion in patients with endometrial cancer.

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC). Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis. Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the "LVSI index" as "TD×%MMI×tumor grade×cervical stromal involvement." The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200. Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.

Minimally invasive surgery for patients with advanced stage endometrial cancer.

Objective: Compare the oncologic outcomes of patients with advanced stage endometrial cancer who were staged by minimally invasive surgery with the outcomes of patients who underwent open surgery. Methods: Data from 138 patients with advanced stage endometrial cancer who were treated between January 2009 and January 2019 were reviewed. The patients' data were retrieved from five institutions. The patients were divided into two groups: those who underwent open surgery and those who underwent minimally invasive surgery. Tumor characteristics, recurrence rate, disease-free survival, and overall survival were compared according to surgical approach. Results: Among the 138 patients included in this study, 72 underwent open surgery (52.2%) and 66 underwent MIS (47.8%). In patients with advanced-stage endometrial cancer, the recurrence rate was significantly higher among those who underwent open surgery (43.1% vs. 25.8%, p = 0.033). Patients with advanced-stage endometrial cancer who underwent open surgery had a significantly lower disease-free survival (p = 0.029) than those who underwent minimally invasive surgery, however, the overall survival (p = 0.051) was similar between the two groups. Conclusion: Minimally invasive surgery showed better survival outcomes when compared to open surgery in advanced-stage EC patients irrespective of the histologic type.

Preoperative neutrophil-to-lymphocyte, platelet-to-lymphocyte and monocyte-to-lymphocyte ratio as a prognostic factor in non-endometrioid endometrial cancer.

Objective: Evaluate the prognostic value of neutrophil-lymphocyte ratio (NMR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) in patients with non-endometrioid endometrial cancer. Method: Laboratory and clinicopathological data from 118 patients with non-endometrioid endometrial cancer who underwent surgical resection between January 2010 and December 2019 were reviewed. NLR, PLR and MLR were analyzed for correlations with recurrence and survival. The receiver operating characteristic (ROC) curves were generated for the NLR, PLR, and MLR. Optimal cut-off values were determined as the points at which the Youden index (sensitivity + specificity - 1) was maximal. Based on the results of the ROC curve analysis, the patients were grouped into high MLR and low MLR groups. Recurrence rate, disease-free survival, and overall survival were compared between the two groups. The prognostic factors were investigated using univariate and multivariate Cox proportional hazards model. Results: The optimal cut-off value of MLR was 0.191 (AUC, 0.718; p < 0.001). Significantly more patients in the high MLR group experienced recurrence (60.3% vs. 15.6%, p < 0.0001) and cancer-related deaths (46.6% vs. 13.3%, p = 0.003). In multivariate analysis, advanced stage and high MLR were independent prognostic factors for disease-free survival and overall survival. Conclusion: Elevated MLR was significantly associated poor clinical outcomes in patients with non endometrioid endometrial cancer. Our findings suggest that MLR may be clinically reliable and useful as an independent prognostic marker for patients with non-endometrioid endometrial cancer.

Higher parity and risk of metabolic syndrome in Korean postmenopausal women: Korea National Health and Nutrition Examination Survey 2010-2012.

AIM: We sought to examine whether parity is associated with higher incidence of metabolic syndrome in postmenopausal women. METHODS: We conducted a cross-sectional study on 4098 Korean postmenopausal women by using nationally representative data from the Korea National Health and Nutrition Examination Survey 2010-2012. Multivariate logistic regression was performed to evaluate the relationship between parity and metabolic syndrome, with adjustment for potential confounding variables. RESULTS: The rate of metabolic syndrome was significantly higher with increasing number of parity, with dose-response relationship in univariate analysis (P <0.001). In addition, higher parity (≥3 live births) was associated with more prevalence of all components of metabolic syndrome compared with two live births (parity 2 vs 3 vs ≥4: 5.5 vs 12.1 and 14.4%, respectively; P < 0.001). However, after adjusting for demographic, socioeconomic, lifestyle and reproductive factors, we found that only higher parity was significantly associated with metabolic syndrome compared with two live births, and failed to show a dose-dependent relationship (parity 2 vs 3 vs ≥4: odds ratio 1 vs 1.404 vs 1.379, respectively; P = 0.043). We also proved that among the components of metabolic syndrome, only waist circumference had a significant positive relationship with parity in a multivariable adjusted model (parity 2 vs 3 vs ≥4: odds ratio 1 vs 1.559 vs 1.656, respectively; P < 0.001). CONCLUSION: Higher parity was independently associated with a higher risk of metabolic syndrome in postmenopausal women.

Does diabetes mellitus have an impact on the prognosis for patients with cervical cancer?

OBJECTIVE: To evaluate the impact of comorbid diabetes mellitus (DM) on prognoses among patients with cervical cancer. METHODS: We analyzed cervical cancer outcomes in patients who treated in two hospitals retrospectively. Patients were divided into those with DM and those without. Clinicopathologic parameters, disease-free survival (DFS), and overall survival (OS) rates were evaluated. RESULTS: Of the 494 patients, 50 had DM. These were more likely to be older than those in the non-DM group and their body mass index (BMI) was higher. They showed higher levels of tumor markers and had more combined diseases. They were less likely to have had surgical treatment. Among these patients, 12 (24%) experienced a recurrence (hazard ratio, HR, 1.484; 95% confidence interval, CI, 0.746-2.951). Differences in DFS did not show statistical significance. In the OS analysis, 11 (22%) in the DM group and 62 (14%) in the non-DM group died (HR, 1.239; 95% CI, 0.606-2.533). No statistically significant differences were also observed for cancer-specific death (HR, 1.246; 95% CI, 0.567-2.737). Those with DM and an adenocarcinoma tended to have an increased risk of dying compared with the non-DM patients with an adenocarcinoma (HR, 3.673; 95% CI, 0.990-13.625), but this difference was not statistically significant (p=0.0518). CONCLUSION: Diabetes mellitus did not have an impact on the prognosis for patients with cervical cancers. In those with an adenocarcinoma, patients with diabetes tended to have an increased risk of dying compared with the non-DM group, but this difference was not statistically significant.

Is neoadjuvant chemotherapy followed by radical surgery more effective than radiation therapy for stage IIB cervical cancer?

OBJECTIVE: The primary objective of the study was to compare the survival rate of patients who had received neoadjuvant chemotherapy with that of patients who had received radiation therapy for stage IIB cervical cancer. The secondary objective was to analyze the effect of neoadjuvant chemotherapy on pathological prognostic factors. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who had received therapy for stage IIB cervical cancer. Based on the primary therapy, 192 patients were divided into 2 groups; patients in the neoadjuvant chemotherapy group (n =103) underwent a type III radical hysterectomy after completion of the neoadjuvant chemotherapy. Patients in the other group (n = 89) were treated with radiation alone or a combination of chemotherapy and radiotherapy. RESULTS: After neoadjuvant chemotherapy, the level of squamous cell carcinoma antigen, tumor size, lymph node involvement, and parametrium involvement were significantly decreased. However, 90.3% of the patients who had received neoadjuvant chemotherapy needed to have adjuvant therapy after radical surgery because of poor pathological prognostic factors. The rate of disease-free survival did not differ significantly between the 2 groups. However, the overall survival rate was significantly lower in the neoadjuvant chemotherapy group for patients who were 60 years or older (P = 0.03). The rates of disease-free survival and overall survival for patients who had a good (complete or partial) response to the neoadjuvant chemotherapy were not significantly higher than the rates for patients in the radiation therapy group. CONCLUSIONS: Although neoadjuvant chemotherapy improved pathological prognostic factors in patients with stage IIB cervical cancer, it was not sufficiently effective to decrease adjuvant therapy. Neoadjuvant chemotherapy also did not improve the rate of patient survival compared to the rate of patient survival in the radiation therapy group.

Laparoscopic colposuspension to the Cooper's ligament after hysterectomy for uterovaginal prolapse.

AIM: The goal of this study was to evaluate the long-term outcomes of laparoscopic colposuspension to the Cooper's ligament after hysterectomy for uterovaginal prolapse. MATERIAL AND METHODS: We performed chart reviews of 43 patients with uterovaginal prolapse who underwent laparoscopic colposuspension to the Cooper's ligament after hysterectomy at Daejeon St. Mary's Hospital, Catholic University of Korea from 2003 to 2009. These patients exhibited grade 3 (29 patients) or grade 4 (14 patients) uterovaginal prolapse. RESULTS: The mean age was 63.2 years (range, 39-76). The mean follow-up period was 44.2 months (95% CI, 36.8-51.5). Forty-three patients showed no sign or recurrence of prolapse. Postoperative complications were tolerable and curable. Urinary frequency (2 patients, 4.7%), voiding difficulty (2 patients, 4.7%), nocturia (1 patient, 2.3%) and vaginal spotting (1 patient, 2.3%) were reported. CONCLUSION: Laparoscopic colposuspension using Cooper's ligament after hysterectomy could be an effective surgical option for the treatment of uterovaginal prolapse.

Nectin-4 as a Predictive Marker for Poor Prognosis of Endometrial Cancer with Mismatch Repair Impairment.

The adhesion molecule Nectin-4 is a new potential therapeutic target for different types of cancer; however, little is known about its diagnosis significance in endometrial cancer (EC). We found that Nectin-4 expression was significantly higher in EC tissues than in nonadjacent normal tissue. The area under the receiver operating characteristic curve value of 0.922 indicated good diagnostic accuracy for Nectin-4 expression in EC. Furthermore, Nectin-4 expression was associated with DNA mismatch repair (MMR) protein deficiency. Notably, the high Nectin-4 expression group of patients with MSH2/6-deficient EC had shorter progression-free survival than that of the low Nectin-4 expression group. The number of lymphovascular space invasion-positive patients in groups with MMR deficiency and high Nectin-4 expression was also increased compared with that in the low Nectin-4 expression group. Bioinformatics analysis revealed that alteration in Nectin-4 and MMR genes is associated with Nectin-4 expression in EC. To the best of our knowledge, this is the first study to show that Nectin-4 expression may be a potential biomarker for EC diagnosis and that high Nectin-4 expression in MMR-deficient patients with EC can predict short progression-free survival, thus providing clues to identify patients for adjuvant therapy.

Prognostic value of ß-Arrestins in combination with glucocorticoid receptor in epithelial ovarian cancer.

Hormones may be key factors driving cancer development, and epidemiological findings suggest that steroid hormones play a crucial role in ovarian tumorigenesis. We demonstrated that high glucocorticoid receptor (GR) expression is associated with a poor prognosis of epithelial ovarian cancer. Recent studies have shown that the GR affects ß-arrestin expression, and vice versa. Hence, we assessed the clinical significance of ß-arrestin expression in ovarian cancer and determined whether ß-arrestin and the GR synergistically have clinical significance and value as prognostic factors. We evaluated the expression of ß-arrestins 1 and 2 and the GR in 169 patients with primary epithelial ovarian cancer using immunohistochemistry. The staining intensity was graded on a scale of 0-4 and multiplied by the percentage of positive cells. We divided the samples into two categories based on the expression levels. ß-arrestin 1 and GR expression showed a moderate correlation, whereas ß-arrestin 2 and GR expression did not demonstrate any correlation. Patients with high ß-arrestin 1 and 2 expression exhibited improved survival rates, whereas patients with low GR expression showed a better survival rate. Patients with high ß-arrestin 1 and low GR levels had the best prognosis among all groups. ß-arrestin is highly expressed in ovarian cancer, suggesting its potential as a diagnostic and therapeutic biomarker. The combination of ß-arrestin and GR demonstrated greater predictive prognostic power than GR expression alone, implicating another possible role in prognostication.

Prognostic Significance of Clinical Factors Including BRCA Mutation in Epithelial Ovarian, Peritoneal, Fallopian Tube Cancer.

BACKGROUND/AIM: We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. PATIENTS AND METHODS: We included patients who had been diagnosed with and treated for epithelial ovarian, peritoneal, or fallopian tube cancer and had undergone germline BRCA testing in six hospitals between January 2012 and December 2019. RESULTS: Of the 378 identified patients, 76 (20.1%) carried a BRCA1/2 mutation. Progression-free survival (PFS) and overall survival (OS) did not differ between patients with and without BRCA1/2 mutation. Multivariate analysis for 18 months after the primary treatment showed higher PFS in the BRCA1/2 mutation group (p=0.024). Subgroup analysis in patients with high-grade serous carcinoma showed that BRCA1/2 mutation was an independent favorable prognostic factor for PFS (p=0.035). Subgroup analysis of patients with stage III or IV disease demonstrated an independent gain in PFS in patients with BRCA1/2 mutation (p=0.015). Neoadjuvant chemotherapy as a primary treatment was related to poor PFS (p<0.001) and reduced OS (p=0.005). CONCLUSION: Having a germline BRCA1/2 mutation improved short-term PFS in patients with epithelial ovarian, peritoneal, or fallopian tube cancer. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.

Oncologic safety of minimally invasive surgery in non-endometrioid endometrial cancer.

OBJECTIVE: This study was aimed to compare the oncologic outcomes of patients with non-endometrioid endometrial cancer who underwent minimally invasive surgery with the outcomes of patients who underwent open surgery. METHOD: This is a retrospective, multi-institutional study of patients with non-endometrioid endometrial cancer who were surgically staged by either minimally invasive surgery or open surgery. Oncologic outcomes of the patients were compared according to surgical approach. RESULTS: 113 patients met the inclusion and exclusion criteria. 57 underwent minimally invasive surgery and 56 underwent open surgery. Patients who underwent minimally invasive surgery had smaller tumors (median size, 3.3 vs. 5.2%, p = 0.0001) and a lower lymphovascular space invasion rate (29.8% vs. 48.2%, p = 0.045). In the overall population, the numbers and rate of recurrence were significantly higher in the open surgery group (p = 0.016). In multivariate analysis, disease stage and tumor size were associated with DFS in contrast to surgical procedure. CONCLUSION: Minimally invasive surgery showed similar survival outcomes when compared to open surgery in non-endometrioid endometrial cancer patients, irrespective of disease stage. When minimally invasive surgery is managed by expert surgeons, non-endometrioid histological subtypes should not be considered a contraindication for minimally invasive surgery.

Weekly cisplatin therapy compared with triweekly combination chemotherapy as concurrent adjuvant chemoradiation therapy after radical hysterectomy for cervical cancer.

OBJECTIVE: To evaluate whether the use of triweekly combination chemotherapy together with radiation exerts a more beneficial systemic effect than weekly cisplatin chemoradiation in patients with cervical cancer after radical surgery. METHODS: We retrospectively analyzed patients with stage IB1 to stage IIB cervical cancer who had undergone radical hysterectomy with pelvic lymph node dissection, followed by concurrent adjuvant chemoradiation therapy. The patients were divided into 2 groups: the triweekly combination chemotherapy group and the weekly cisplatin chemotherapy group. We evaluated the survival and adverse effects of the 2 groups. RESULTS: In total, 201 patients were included. The mean duration of follow-up was 52.2 months. Of the 201 patients, 130 received triweekly combination chemotherapy, and 71 patients received weekly cisplatin chemotherapy as an adjuvant treatment. The 5-year disease-free survival was 82.2% for patients treated with weekly cisplatin chemotherapy and 74.3% for those treated with triweekly combination chemotherapy (P = 0.3929). The 5-year overall survival was 81.4% and 79.3% for the same treatment groups, respectively (P = 0.9833). The overall survival of the patients with stage IIB cervical cancer was marginally higher in the triweekly combination chemotherapy group than in the weekly cisplatin group (P = 0.0582). Leukopenia, neutropenia, thrombocytopenia, anemia, and hepatopathy were significantly more common in the triweekly combination chemotherapy group. CONCLUSIONS: The weekly cisplatin chemotherapy group experienced the same therapeutic effect as the triweekly combination chemotherapy group but with less toxicity. Therefore, weekly cisplatin chemotherapy is considered the more useful concurrent adjuvant chemoradiation regimen after radical surgery.

Does intraabdominal pressure affect development of subcutaneous emphysema at gynecologic laparoscopy?

STUDY OBJECTIVE: To estimate the effect of intraabdominal pressure and risk factors related to the occurrence of subcutaneous emphysema during laparoscopic surgery. DESIGN: Prospective randomized study (Canadian Task Force classification I). SETTING: University hospital. PATIENTS: Two hundred patients who underwent gynecologic laparoscopy because of benign gynecologic disease or cervical intraepithelial neoplasia. INTERVENTIONS: Gynecologic laparoscopy. MEASUREMENTS AND MAIN RESULTS: Before surgery, patients were divided randomly into 2 groups. During surgery, the first group were limited to 12 mm Hg intraabdominal pressure (n = 100), and the second group 10 mm Hg intraabdominal pressure (n = 100). The incidence of subcutaneous emphysema in each group and the relationship between subcutaneous emphysema and operation time, table tilt angle, patient age, body mass index (BMI) and end-tidal CO(2) (ETco(2)) were analyzed. The occurrence of subcutaneous emphysema was significantly lower in the group 2 than in group 1 (p = .02). The BMI was significantly lower (p = .02), and peak ETco(2) significantly higher (p < .001) in the group in which subcutaneous emphysema developed. However, there were no significant differences in age, operative time, table tilt angle, number of ports used, and initial ETco(2) between the groups with and without subcutaneous emphysema. CONCLUSIONS: The incidence of subcutaneous emphysema increased with higher intraabdominal pressure during gynecology laparoscopy. Low BMI and increased intraoperative ETco(2) concentration were also related to the occurrence of subcutaneous emphysema.

Dual inhibition of FOXM1 and its compensatory signaling pathway decreased the survival of ovarian cancer cells.

The present study aimed to analyze the compensatory signaling pathways induced by forkhead domain inhibitor­6 (FDI­6), which is a forkhead box protein M1 (FOXM1) inhibitor, in ovarian cancer cells and evaluate the effectiveness of simultaneous inhibition of FOXM1 and the compensatory signaling pathway in decreasing the survival of ovarian cancer cells. The present study identified the proteins involved in the compensatory mechanism activated by FDI­6 in HeyA8 ovarian cancer cells using western blot analysis and a reverse­phase protein array. In addition, a cell viability assay was performed to determine the effects of FDI­6 and the compensatory signaling pathway on cancer cell viability. All experiments were performed in three­dimensional cell cultures. The present study observed that FDI­6 stimulated the upregulation of N­Ras, phosphoprotein kinase Cδ (p­PKCδ) (S664) and HER3 in HeyA8 cells. Tipifarnib as an N­Ras inhibitor, rottlerin as a p­PKCδ (S664) inhibitor and sapitinib as a HER3 inhibitor were selected. The combination of FDI­6 with tipifarnib attenuated the upregulation of N­Ras induced by FDI­6 and the combination of FDI­6 with sapitinib also attenuated HER3 downstream signaling pathway in HeyA8 cells, as shown by on western blot analysis. Rottlerin downregulated p­PKCδ (S664) by inhibiting the activity of a Src­related tyrosine kinase that transfers a phosphate group to PKCδ. Compared with FDI­6 alone, the addition of tipifarnib or rottlerin to FDI­6 was significantly more effective in reducing the growth of HeyA8 cells. However, the combination of FDI­6 and sapitinib did not induce a significant decrease in survival of HeyA8 cells. In conclusion, the addition of tipifarnib or rottlerin to inhibit N­Ras or p­PKCδ (S664), respectively, inhibited the compensatory signaling pathway response induced by FDI­6 in HeyA8 cells. These inhibitors increased the efficacy of FDI­6, which inhibits FOXM1, in reducing ovarian cancer cell viability.

Low serum T3 levels are associated with false-positive results when using the risk of ovarian malignancy algorithm (ROMA) in women with benign ovarian disease.

OBJECTIVE: We investigated factors that could cause false-positive results when using the risk of ovarian malignancy algorithm (ROMA) for assessing ovarian cancer risk. MATERIALS AND METHODS: ROMA scores were calculated from patients followed surgery to remove a pelvic mass. We compared a false-positive group with a true-negative group of ROMA scores. RESULTS: We analyzed 324 patients using medical records. There were 22 with an epithelial ovarian cancer (EOC), 15 with a borderline ovarian tumor, and 287 with benign disease. Twenty-nine (10.1%) of the patients with benign disease showed high-risk ROMA score (false positive) and 13/37 (35%) patients with EOC, or borderline ovarian tumor showed low ROMA scores (false negatives). The median serum triiodothyronine (T3) level of the false-positive ROMA group in patients with benign disease was lower than in the true-negative ROMA group (p < 0.001) and the estimated glomerular filtration rate (eGFR) was also lower (p = 0.001) in the false-positive ROMA group. Median serum T3 levels in the true-positive ROMA group among patients with EOC, or borderline ovarian tumor were lower than in the false-negative ROMA group (p = 0.043). CONCLUSION: Median serum T3 level and eGFR in the false-positive ROMA group in patients with benign ovarian disease were lower than in the true-negative group.

Does the type of hysterectomy affect the prognosis in clinical stage I endometrial cancer?

AIM: To determine whether clinical outcomes show a benefit from extended hysterectomy in patients with early endometrial cancer. METHODS: We reviewed the medical records of 101 patients who had endometrial cancer with clinical stage I disease. All the patients were surgically staged, and two types of hysterectomy, simple hysterectomy (SH) or extended hysterectomy (EH), were performed by surgeon's preference. The postoperative pathology findings, recurrence rate and disease-free survivals (DFS) between the two groups were compared. RESULTS: Sixty-six patients and thirty-five patients underwent SH and EH, respectively. At subsequent surgical staging, seven patients (10.6%) in the SH and four (11.4%) in EH group were upgraded to stage II or III disease. The surgical and pathological features were not different between the groups. Though the recurrence rate was lower in the EH group (9.09% for SH vs 2.86% for EH), it showed no statistical significance (P = 0.241). The 5-year DFS (88.2% for SH vs 96.0% for EH) showed no statistically significant difference between the groups either (P = 0.242). CONCLUSION: Compared to SH, EH did not have any prognostic benefit in clinical stage I endometrial cancer. Until the therapeutic role of the EH is determined by further studies using a larger sample size, SH remains the treatment of choice in patients with early endometrial cancer, and surgeons should not perform extended operation without definite evidence of the disease.

A prospective comparison of vaginal stump suturing techniques during total laparoscopic hysterectomy.

PURPOSE: We compared the incidence of vaginal cuff dehiscence and other surgical complications after different modes of suturing during total laparoscopic hysterectomy (TLH), and reviewed the characteristics of patients with complications. METHODS: We enrolled 248 patients undergoing TLH for benign diseases at Daejeon St Mary's Hospital of Korea from March 2007 through February 2009. We evaluated the clinical outcomes of different vaginal cuff suture techniques during TLH: the widely used interrupted figure-of-eight suture and a two-layer running suture. RESULTS: All operations were completed successfully by laparoscopy. Three of 248 hysterectomies (1.2%) were complicated by vaginal cuff dehiscence. One of them belonged to the two-layer running suture group, and the others belonged to the interrupted figure-of-eight suture group. However, there was no statistically significant difference in outcomes between the suture methods. One case of trocar site incisional herniation occurred. No ureteral, bladder, or major vascular injury occurred. The overall major complication rate including vaginal bleeding was 2.0% (5/248). CONCLUSIONS: The two-layer running suture technique was safe and effective for vaginal cuff suture during TLH, but there was no statistically significant advantage over the widely used figure-of-eight suture method. Diabetes, cigarette smoking and pelvic adhesions produced statistically significant increased risks of complication.