Epithelial ovarian cancer in younger age versus older age groups: Survival and clinicopathological features.

OBJECTIVES: This study aimed to analyze the survivals and clinicopathological features of epithelial ovarian cancer (EOC) in younger age patients and to determine the impact of age on survival. METHODS: EOC patients aged ≤40 years were matched to patients aged >40 years at a 1:4 ratio. Disease-specific survival (DSS), progression-free survival (PFS), and clinicopathological and treatment features were compared between patients aged ≤40 and >40 years. RESULTS: A total of 763 EOC patients were reviewed. During a median follow-up period of 41 (range, 1-195) months, EOC patients aged ≤40 and >40 years did not show any statistically significant difference in median DSS (120 versusversus 84.7 months; hazard ratio, 0.78; 95% confidence interval, 0.58, 1.06); however, the median PFS was better in patients aged ≤40 years (median PFS not reached versusversus 41 months; HR, 0.65; 95% CI, 0.5, 0.85). Age ≤40 years was an independent favorable prognostic factor for DSS at 3 years after diagnosis. In contrast, younger age was an independent poor prognostic factor prior to this time point. EOC patients aged ≤40 years exhibited a significantly higher rate of early-stage disease, a higher proportion of mucinous subtype, and lower cancer antigen-125 level. CONCLUSION: Overall, EOC patients in the younger age group were associated with more favorable prognostic factors and showed better PFS, but not DSS, than those in the older age group. Younger age was identified as an unfavorable prognostic factor within 3 years of diagnosis and became a favorable prognostic factor after 3 years.

Impact of appendectomy of a grossly normal appendix on the survival outcomes of mucinous ovarian carcinomas in a tertiary hospital.

OBJECTIVE: To evaluate the survival outcomes of appendectomy for a grossly normal appendix in patients with mucinous ovarian carcinomas. METHODS: Retrospective cohort study. Patients with mucinous ovarian carcinomas with grossly normal appendices who underwent primary surgery between 2002 and 2022 were enrolled. The overall survival (OS) and progression-free survival (PFS) of appendectomy and non-appendectomy groups were analyzed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox regression analyses were used to determine the independent factors associated with OS and PFS. RESULTS: Of 192 patients, appendectomy was performed in 138 (71.9%). Three (1.6%) patients had primary appendiceal tumors and two (1.0%) had appendiceal metastases of ovarian origin. The median follow-up time was 68.8 months. The OS and PFS were better in patients in the appendectomy group than in those in the non-appendectomy group (5-year OS: 80.72% vs. 65.05%, P = 0.012; 5-year PFS: 76.32% vs. 58.60%, P = 0.020). Independent factors associated with poor OS and PFS were no omentectomy, peritoneal seeding, and advanced International Federation of Gynecology and Obstetrics (FIGO) stage. CONCLUSION: Appendectomy of a grossly normal appendix was not an independent prognostic factor for OS and PFS in patients with mucinous ovarian carcinomas.

Preoperative modified frailty index to predict surgical complications in endometrial cancer patients.

OBJECTIVE: To assess the predictive value of the preoperative modified frailty index (mFI) for postoperative complications in endometrial carcinoma, evaluate risk factors associated with complications, and compare the predictive properties of the mFI with the American Society of Anesthesiologists (ASA) physical status classification. METHODS: A total of 364 patients with endometrial cancer who underwent primary surgery between January 2009 and December 2016 were examined. The prognostic value of mFI in predicting severe postoperative complications, assessed according to the Clavien-Dindo classification, was analyzed and compared with ASA status. The risk factors for adverse outcomes were determined using multivariate analysis. RESULTS: The 30-day postoperative surgical- or medical-related complication rate was 26.6%. The rates of postoperative complications were 1.3%, 8.8%, 12.2%, and 60.0% for mFI scores of 0, 1, 2, and ≥3, respectively (P<0.001). The odds ratios for predicting postoperative complications in patients with mFI scores of 1, 2, and ≥3 were 7.38, 10.59, and 114.75, respectively. In the multivariate analysis, the significant predictive factors for postoperative complications were mFI ≥1, body mass index (BMI) ≥30 kg/m2, and non-endometrioid cell type. At cut-off points of mFI ≥1 and ASA ≥2, both tools had similar sensitivities but mFI was more specific (sensitivities 92.9% vs. 100%; specificity 45.5% vs. 19.4%). CONCLUSION: mFI provides a satisfactory predictive value for postoperative complications. Patients with an mFI score ≥1, a BMI ≥30 kg/m2, and a non-endometrioid subtype, are at risk of postoperative complications and should receive comprehensive preoperative and postoperative management.

Serum human chorionic gonadotropin ratios for the detection of etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine resistance in high-risk gestational trophoblastic neoplasia.

Aims: This study aimed to identify the optimal human chorionic gonadotropin (hCG) ratio in predicting etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine resistance in women diagnosed with high-risk gestational trophoblastic neoplasia (GTN) and to compare the chemoresistant disease detection rate by using the optimal hCG ratio and traditional criteria. Methods: Seventy-six women with primary high-risk GTN treated with etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine in a tertiary-care center were included. The hCG ratio was determined by its serum pretreatment level divided by that before each cycle of chemotherapy. The traditional criteria for chemoresistance included plateau or rising of hCG or presence of new metastasis. The optimal hCG ratio was determined using receiver operating characteristics (ROC) curve analysis. Results: Among the specificities of 90%, 92.5%, and 95%, the 90% specificity yielded the best ROC curve. At 90% specificity, the best area under curve value was at the fourth cycle with 75% sensitivity. The hCG ratio at the fourth cycle was 31.92. Using the ratio at the fourth cycle, chemoresistant disease was detected in six out of eight patients, compared to one in the traditional criteria. When combining the two diagnostic tools, the cumulative detection rate in the fourth cycle was 10/12 (83.3%) of total drug resistance. Among patients who developed drug resistance at the fourth cycle or thereafter, the use of the ratio at the fourth cycle could diagnose chemoresistance approximately two cycles earlier than that with the traditional criteria. Conclusions: A hCG ratio of <31.9 at the fourth cycle should be considered a high-risk for etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine resistance and may need second-line chemotherapy. The ratio increases the detection rate of resistance to these drugs more than the traditional criteria.

Appendiceal tumors in patients undergoing primary surgery for mucinous ovarian tumors in a tertiary hospital, in Southern Thailand.

OBJECTIVE: To evaluate the prevalence of appendiceal tumors in patients diagnosed with mucinous ovarian tumors and to determine factors associated with coexisting appendiceal tumors. MATERIALS AND METHODS: Retrospective review of all patients who were diagnosed with mucinous ovarian tumors and underwent an appendectomy during surgery between January 2002 and June 2017 was performed. Univariate and multivariate logistic regression analyses were used to identify risk factors for coexisting appendiceal tumors. RESULTS: A total of 303 patients with mucinous ovarian tumors who underwent appendectomy were identified, including 77 (25.4%) mucinous cystadenoma and 226 (74.6%) mucinous borderline tumor or carcinoma. Twenty-one (6.9%) had coexisting appendiceal tumors including 8 that were primary appendiceal mucinous adenocarcinomas, 6 low-grade appendiceal mucinous neoplasms, 6 secondary appendiceal metastasis from the ovary, and one hyperplastic polyp. None of mucinous cystadenoma had coexisting appendiceal tumors. Multivariate analysis revealed advanced age ≥50 years, previous rupture of ovarian tumors, abdominal extension of tumors, and grossly abnormal appendix were independent factors for coexisting appendiceal tumors. CONCLUSION: Prevalence of coexisting appendiceal tumors in mucinous ovarian tumors was not uncommon. The risk factors were grossly abnormal appendix, abdominal extension of tumor, previous rupture of ovarian tumors, and advanced age.

Diagnostic Performance and Agreement of Preoperative, Intraoperative Evaluations, and Final Pathology for Lymphadenectomy and Lymph Node Involvement in Endometrial Cancer

Objective: To determine the accuracy of clinical parameters examined by preoperative and intraoperative evaluations compared with final histological results in patients with endometrial cancer, and to evaluate the application of preoperative investigations, intraoperative evaluations, and final histological results in predicting lymph node involvement Material and Method: The medical records of the patients diagnosed with endometrial cancer who had surgical staging between January 1, 2006 and December 31, 2012 at Songklanagarind Hospital were retrospectively reviewed. The agreement of clinical parameters identified through preoperative investigations and intraoperative evaluations with the final histology findings were calculated using kappa statistics. The diagnostic performance of preoperative investigations, intraoperative evaluations, and final histological results to predict lymph node involvement were calculated in terms of sensitivity, specificity, positive predictive value, and negative predictive value. Results: Preoperative investigations showed a slight to fair agreement whereas intraoperative evaluations had a fair to moderate agreement in detecting clinical parameters compared with the final histological results. Endocervical curettage and endometrial biopsy exhibited the highest sensitivity, pelvic ultrasonography the highest specificity, and intraoperative evaluations had a high-level sensitivity and specificity Conclusion: Preoperative investigations have role as an adjunctive evaluation, whereas intraoperative gross assessment remains the most accurate and useful method of detecting patients for lymphadenectomy.

Human Chorionic Gonadotropin (hCG) Regression Curve for Predicting Response to EMA/CO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide and Vincristine) Regimen in Gestational Trophoblastic Neoplasia.

BACKGROUND: An hCG regression curve has been used to predict the natural history and response to chemotherapy in gestational trophoblastic disease. We constructed hCG regression curves in high-risk gestational trophoblastic neoplasia (GTN) treated with EMA/CO and identified an optimal hCG level to detect EMA/CO resistance in GTN. MATERIALS AND METHODS: Eighty-one women with GTN treated with EMA/CO were classified as primary high-risk GTN (n=65) and single agent-resistance GTN (n=16). The hCG levels prior to each course of chemotherapy were plotted in the 10th, 50th, and 90th percentiles to construct the hCG regression curves. Diagnostic performance was evaluated for an optimal cut-off value. RESULTS: The median hCG levels were 264,482 mIU/mL mIU/mL and 495.5 mIU/mL mIU/mL for primary high-risk GTN and single agent-resistance GTN, respectively. The 50th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 4th and the 2nd course of chemotherapy, respectively. The 90th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 9th and the 2nd course of chemotherapy, respectively. The hCG level of ≥118.6 mIU/mL mIU/mL at the 5thcourse of EMA/CO predicted the EMA/CO resistance in primary high-risk GTN patients with a sensitivity of 85.7% and a specificity of 100%. CONCLUSION: EMA/CO resistance in primary high-risk GTN can be predicted by using an hCG regression curve in combination with the cut-off value of 118.6 mIU/mL at the 5thcourse of chemotherapy.

Radiation, chemotherapy or combined modality therapy in adjuvant treatment for stage III endometrial carcinoma in lower southern Thailand: disease recurrence and overall survival.

OBJECTIVE: To survey disease-free survival (DFS) and overall survival (OS) of patients with stage III endometrial carcinoma treated with post-operative radiation and/or chemotherapy MATERIAL AND METHOD: The medical records of patients with surgical stage III endometrial carcinoma, and receiving adjuvant treatment between January 2003 and December 2012 were reviewed DFS and OS were analyzed using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: Of the 54 eligible patients, 61% underwent radiation, 19% chemotherapy, and 20% chemotherapy with radiation. The median DFS was 36.7 months. The 3-year DFS and OS was 51.9% (95% CI 36.3-74.1%) and 70.6% (95% CI 57.4-86.8%), respectively. There was no significant difference in DFS and OS among treatment groups. Cox regression analysis showed grade 2-3 tumors and menopause were associated with poor DFS and OS. CONCLUSION: The DFS and OS in stage III endometrial carcinoma receiving postoperative adjuvant therapy were quite good and were not different among radiation therapy, chemotherapy, and combined treatment groups. The multi-center randomized prospective study was needed to determine the standard modality.

Cytomorphologic and clinical factors of having high-grade cervical intraepithelial neoplasia/invasive carcinoma in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) smears.

OBJECTIVE: To determine the predictors for high-grade cervical intraepithelial neoplasia (CIN)/invasive carcinoma in women with atypical squamous cells, cannot exclude the high-grade squamous intraepithelial lesion (ASC-H) smears. MATERIAL AND METHOD: All women with ASC-H, who underwent colposcopy and had histolopathologic diagnosis between January 2004 and December 2011, were recruited. Clinical and cytomorphologic features were correlated with final histological diagnosis. Univariate and multivariate analysis were used to determine predicting factors for high-grade CIN/ invasive cancer RESULTS: Among 136,638 smears performed, 193 (0.14%) smears were reported as ASC-H and 121 smears were available for review. The underlying pathology were negative/reactive (N/R) 57 (47.1%), CIN 1 23 (19.0%), CIN 2-3 39 (32.0%), and invasive cancer 2 (1.6%). On univariate analysis, predicting factors of having high-grade CIN included a high N/C ratio, greater nuclear hyperchromasia, nuclear membrane irregularities, and the coarse chromatin. The multivariate analysis showed that a high nuclear-to-cytoplasmic (N/C) ratio (OR = 8.6, 95% CI = 1.1-70.1) and greater nuclear hyperchromasia (OR = 5.8, 95% CI = 1.6-20.8) were the independent predictors for high-grade CIN or invasive carcinoma. CONCLUSION: The presence of a high N/C ratio and greater nuclear hyperchromasia could be used to predict high-grade CIN or invasive carcinoma in ASC-H smears.

Effect of continuous education for evidence-based medicine practice on knowledge, attitudes and skills of medical students.

OBJECTIVE: To assess the effect of the integration of evidence-based medicine (EBM) in a medical curriculum using small-group discussions with case scenario and problem-based learning on the knowledge, attitudes and skills of medical students. METHOD: A quasi-experimental study was conducted in a medical school in southern Thailand during 2008-2009. EBM practice was begun before the completion of the fourth year using case scenario and continued through the fifth year using learner-centred, problem-based self-practice. Knowledge improvement was measured by summative assessment using pre- and post-tests after small-group discussions with a case scenario. Attitudes and skills were measured by self-rating assessments: before initiation of the course (T0) and after the course at week 1, 5, 13, 25 and 37 (T1, T2, T3, T4 and T5), respectively. Data were analyzed using paired t-test and linear mixed-effects model fitted by maximum likelihood. RESULTS: One hundred fourteen students took the course, with a mean age of 22.1 years. Before and after knowledge scores showed a significant improvement (4.93 versus 7.43). The proportion of students who achieved the highest knowledge scores was higher (4% at pre-test versus 54% at post-test). Both self-rated attitudes and skills after EBM practice increased dramatically from the initiation of the course (T0; P < 0.001). Compared with T1, significantly lower scores of attitudes and skills were observed at T2 and T3, but both were higher at T4 assessment. CONCLUSIONS: Continuous EBM education through small-group discussion and learner-centred, problem-based self-practice can be a useful way to improve a medical student's knowledge, attitudes and skills.

Correlation of p53 and Ki-67 (MIB-1) expressions with clinicopathological features and prognosis of early stage cervical squamous cell carcinomas.

AIM: To evaluate the prognostic significance of the expression of p53 and Ki-67, and their correlation with various clinicopathological factors in patients with squamous cell carcinoma of the uterine cervix treated by radical hysterectomy. METHODS: Two hundred and thirty five patients diagnosed between 1987 and 2004 were investigated for p53 and Ki-67 expression by immunohistochemistry. The relationship of these proteins and other potential prognostic factors with recurrence-free survival (RFS) was evaluated. RESULTS: The mean age of the patients was 43.9 years (range, 27-68). There were 28 cases with stage IA2 (11.9%) and 207 cases with stage IB1 (88.1%). The overall 5-year RFS was 91.1% (95% confidence interval [CI] 86.0, 94.4). p53 and Ki-67 expressions were seen in 33.6% and 81.3% of cases, respectively. p53 expression was significantly associated only with parametrial or marginal involvement (P = 0.005), while Ki-67 expression significantly correlated only with larger tumor (P = 0.011) and parametrial or marginal involvement (P = 0.024). There was significant correlation between the expression of p53 and Ki-67 (P = 0.021). In multivariate analysis, Ki-67 expression (hazard ratio for >or=3rd vs 1st tertile [>or=30% vs <20% expression] = 16.0, 95%CI 2.1-124.5; P = 0.0015) appeared to be an independent prognostic factor for RFS, while no prognostic significance of p53 expression was found. CONCLUSION: Ki-67 expression is an independent prognostic parameter for RFS in patients with early stage squamous cell carcinoma of the uterine cervix. Ki-67 expression at or above the cut-off point of 30.0% had significantly poorer RFS.

Predictors of the residual disease of high-grade lesions and microinvasive squamous cell carcinoma of the cervix following conization.

OBJECTIVE: To determine the predictors of residual disease of high-grade lesion (HGL) and microinvasive squamous cell carcinoma of the cervix (MICA) in subsequent hysterectomy following conization. MATERIAL AND METHOD: The medical records of women who underwent any conizations diagnosed of HGL and MICA and followed by subsequent hysterectomy within 6 months were retrospectively reviewed. A case and control was defined as whether or not a residual disease of HGL or more was detected in cervical tissue from hysterectomy after conization. Demographic characteristics and pathological features of cases and controls were recorded independently and blindly. Univariate and multivariate analysis were used. The Receiver Operating Characteristics curve of predictors was created using the fitting value obtained from a logistic regression model. RESULTS: A total of 185 women were diagnosed during January 1, 1997 and July 31, 2008 including 102 women without a residual disease and 83 with residual disease at cervical tissue from hysterectomy. The multivariate analysis showed that postmenopausal status (OR = 3.5, 95% CI = 1.8-6.7), number of quadrant involvement (OR = 3.8, 95% CI = 1.8-8.3), internal margin involvement (OR = 3.8, 95% CI = 1.7-8.2), severe nuclear atypia (OR = 2.0, 95% CI = 1.1-3.8) and high mitotic activity (OR = 2.1, 95% CI = 1.1-3.7) were the predictors of residual disease in hysterectomy specimens after conization. Three or more predictors involved predicted the detection of residual disease. CONCLUSION: The presence of postmenopause, three or four quadrants involved, positive internal margin, severe nuclear atypia and high mitotic activity could be used to predict residual lesions after conization.