Relationships of nuclear, architectural and International Federation of Gynecology and Obstetrics grading systems in endometrial cancer.

PubMed

Toptaş, Tayfun; Peştereli, Elif; Bozkurt, Selen; Erdoğan, Gülgün; Şimşek, Tayup

2018-03-01

To examine correlations among nuclear, architectural, and International Federation of Gynecology and Obstetrics (FIGO) grading systems, and their relationships with lymph node (LN) involvement in endometrioid endometrial cancer. Histopathology slides of 135 consecutive patients were reviewed with respect to tumor grade and LN metastasis. Notable nuclear atypia was defined as grade 3 nuclei. FIGO grade was established by raising the architectural grade (AG) by one grade when the tumor was composed of cells with nuclear grade (NG) 3. Correlations between the grading systems were analyzed using Spearman's rank correlation coefficients, and relationships of grading systems with LN involvement were assessed using logistic regression analysis. Correlation analysis revealed a significant and strongly positive relationship between FIGO and architectural grading systems (r=0.885, p=0.001); however, correlations of nuclear grading with the architectural (r=0.535, p=0.165) and FIGO grading systems (r=0.589, p=0.082) were moderate and statistically non-significant. Twenty-five (18.5%) patients had LN metastasis. LN involvement rates differed significantly between tumors with AG 1 and those with AG 2, and tumors with FIGO grade 1 and those with FIGO grade 2. In contrast, although the difference in LN involvement rates failed to reach statistical significance between tumors with NG 1 and those with NG 2, it was significant between NG 2 and NG 3 (p=0.042). Although all three grading systems were associated with LN involvement in univariate analyses, an independent relationship could not be established after adjustment for other confounders in multivariate analysis. Nuclear grading is significantly correlated with neither architectural nor FIGO grading systems. The differences in LN involvement rates in the nuclear grading system reach significance only in the setting of tumor cells with NG 3; however, none of the grading systems was an independent predictor of LN involvement.

Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Almstedt, Katrin; Heimes, Anne-Sophie; Makris, Georgios-Marios; Weyer, Veronika; Schmidt, Marcus

2016-09-01

New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p = 0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p = 0.025). The MDACC grading system (p = 0.008) but not the FIGO system (p = 0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95 % CI 1.007-2.449; p = 0.047, and HR 0.712; 95 % CI 0.476-1.066; p = 0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95 % CI 1.207-3.835; p = 0.009, and HR 1.258; 95 % CI 0.801-1.975; p = 0.319, respectively). We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system.

Individualized Prediction of Overall Survival After Postoperative Radiation Therapy in Patients With Early-Stage Cervical Cancer: A Korean Radiation Oncology Group Study (KROG 13-03)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Hyun Jin; Han, Seungbong; Kim, Young Seok, E-mail: ysk@amc.seoul.kr

Purpose: A nomogram is a predictive statistical model that generates the continuous probability of a clinical event such as death or recurrence. The aim of the study was to construct a nomogram to predict 5-year overall survival after postoperative radiation therapy for stage IB to IIA cervical cancer. Methods and Materials: The clinical data from 1702 patients with early-stage cervical cancer, treated at 10 participating hospitals from 1990 to 2011, were reviewed to develop a prediction nomogram based on the Cox proportional hazards model. Demographic, clinical, and pathologic variables were included and analyzed to formulate the nomogram. The discrimination andmore » calibration power of the model was measured using a concordance index (c-index) and calibration curve. Results: The median follow-up period for surviving patients was 75.6 months, and the 5-year overall survival probability was 87.1%. The final model was constructed using the following variables: age, number of positive pelvic lymph nodes, parametrial invasion, lymphovascular invasion, and the use of concurrent chemotherapy. The nomogram predicted the 5-year overall survival with a c-index of 0.69, which was superior to the predictive power of the International Federation of Gynecology and Obstetrics (FIGO) staging system (c-index of 0.54). Conclusions: A survival-predicting nomogram that offers an accurate level of prediction and discrimination was developed based on a large multi-center study. The model may be more useful than the FIGO staging system for counseling individual patients regarding prognosis.« less

[Multiparameter magnetic resonance imaging in the diagnosis of cancer of the cervix uteri].

PubMed

Tarachkova, E V; Strel'tsova, O N; Panov, V O; Bazaeva, I Ya; Tyurin, I E

2015-01-01

Cancer of the cervix uteri (CCU) ranks third in the incidence of malignancies in women. The choice of CCU treatment mainly depends on the extent of the tumor process, i.e., the stage of the disease. Determining the stage of CCU is based on the clinical classification of the International Federation of Gynecology and Obstetrics (FIGO) (2009) and has a number of substantial limitations in evaluating parametrial invasion, tumor spread to the pelvic wall, and involvement of regional lymph nodes and in determining the true tumor sizes. Magnetic resonance imaging (MRI) is now the method of choice in staging invasive CCU. Multiparameter MRI will be able to enhance the efficiency of diagnosing microinvasive CCU as well (FIGO 2009), to plan surgical and/or chemoradiation treatment, to evaluate its efficiency, and to diagnose locally recurrent CCU.

The Role of Vaginal Brachytherapy in the Treatment of Surgical Stage I Papillary Serous or Clear Cell Endometrial Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barney, Brandon M., E-mail: barney.brandon@mayo.edu; Petersen, Ivy A.; Mariani, Andrea

2013-01-01

Objectives: The optimal adjuvant therapy for International Federation of Gynecology and Obstetrics (FIGO) stage I papillary serous (UPSC) or clear cell (CC) endometrial cancer is unknown. We report on the largest single-institution experience using adjuvant high-dose-rate vaginal brachytherapy (VBT) for surgically staged women with FIGO stage I UPSC or CC endometrial cancer. Methods and Materials: From 1998-2011, 103 women with FIGO 2009 stage I UPSC (n=74), CC (n=21), or mixed UPSC/CC (n=8) endometrial cancer underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant high-dose-rate VBT. Nearly all patients (n=98, 95%) also underwent extended lymph node dissection of pelvic andmore » paraortic lymph nodes. All VBT was performed with a vaginal cylinder, treating to a dose of 2100 cGy in 3 fractions. Thirty-five patients (34%) also received adjuvant chemotherapy. Results: At a median follow-up time of 36 months (range, 1-146 months), 2 patients had experienced vaginal recurrence, and the 5-year Kaplan Meier estimate of vaginal recurrence was 3%. The rates of isolated pelvic recurrence, locoregional recurrence (vaginal + pelvic), and extrapelvic recurrence (including intraabdominal) were similarly low, with 5-year Kaplan-Meier estimates of 4%, 7%, and 10%, respectively. The estimated 5-year overall survival was 84%. On univariate analysis, delivery of chemotherapy did not affect recurrence or survival. Conclusions: VBT is effective at preventing vaginal relapse in women with surgical stage I UPSC or CC endometrial cancer. In this cohort of patients who underwent comprehensive surgical staging, the risk of isolated pelvic or extrapelvic relapse was low, implying that more extensive adjuvant radiation therapy is likely unnecessary.« less

New FIGO and Swedish intrapartum cardiotocography classification systems incorporated in the fetal ECG ST analysis (STAN) interpretation algorithm: agreements and discrepancies in cardiotocography classification and evaluation of significant ST events.

PubMed

Olofsson, Per; Norén, Håkan; Carlsson, Ann

2018-02-01

The updated intrapartum cardiotocography (CTG) classification system by FIGO in 2015 (FIGO2015) and the FIGO2015-approached classification by the Swedish Society of Obstetricians and Gynecologist in 2017 (SSOG2017) are not harmonized with the fetal ECG ST analysis (STAN) algorithm from 2007 (STAN2007). The study aimed to reveal homogeneity and agreement between the systems in classifying CTG and ST events, and relate them to maternal and perinatal outcomes. Among CTG traces with ST events, 100 traces originally classified as normal, 100 as suspicious and 100 as pathological were randomly selected from a STAN database and classified by two experts in consensus. Homogeneity and agreement statistics between the CTG classifications were performed. Maternal and perinatal outcomes were evaluated in cases with clinically hidden ST data (n = 151). A two-tailed p < 0.05 was regarded as significant. For CTG classes, the heterogeneity was significant between the old and new systems, and agreements were moderate to strong (proportion of agreement, kappa index 0.70-0.86). Between the new classifications, heterogeneity was significant and agreements strong (0.90, 0.92). For significant ST events, heterogeneities were significant and agreements moderate to almost perfect (STAN2007 vs. FIGO2015 0.86, 0.72; STAN2007 vs. SSOG2017 0.92, 0.84; FIGO2015 vs. SSOG2017 0.94, 0.87). Significant ST events occurred more often combined with STAN2007 than with FIGO2015 classification, but not with SSOG2017; correct identification of adverse outcomes was not significantly different between the systems. There are discrepancies in the classification of CTG patterns and significant ST events between the old and new systems. The clinical relevance of the findings remains to be shown. © 2017 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Outcomes of fertility-sparing surgery among young women with FIGO stage I clear cell carcinoma of the ovary.

PubMed

Park, Jeong-Yeol; Suh, Dae-Shik; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun

2016-07-01

To evaluate the outcome of fertility-sparing surgery among young women with early-stage clear cell carcinoma of the ovary. In a retrospective study, data were reviewed for patients aged 45years or younger who had FIGO stage I clear cell carcinoma of the ovary and had attended one institution in South Korea between December 1999 and December 2009. Outcomes were compared between women undergoing fertility-sparing surgery, defined as preservation of the uterus and at least one adnexa, and those undergoing radical surgery. Overall, 47 patients were included (22 underwent fertility-sparing surgery, 25 radical surgery). After a median follow-up of 72months (range 8-175), 5 (23%) patients who underwent fertility-sparing surgery and 5 (20%) in the radical surgery group had recurrent disease (P=0.820). The mean time to recurrence was 19months after fertility-sparing surgery versus 20months after radical surgery (P=0.935). The anatomical location of recurrence did not differ. There was no difference in 5-year disease-free survival (77% vs 84%; P=0.849) or 5-year overall survival (91% vs 88%; P=0.480). Fertility-sparing surgery was found to be a safe alternative for young women with FIGO stage I clear cell carcinoma of the ovary who wish to preserve fertility. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study.

PubMed

Bodurka, Diane C; Deavers, Michael T; Tian, Chunqiao; Sun, Charlotte C; Malpica, Anais; Coleman, Robert L; Lu, Karen H; Sood, Anil K; Birrer, Michael J; Ozols, Robert; Baergen, Rebecca; Emerson, Robert E; Steinhoff, Margaret; Behmaram, Behnaz; Rasty, Golnar; Gershenson, David M

2012-06-15

A study was undertaken to use the 2-tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3-tier system and determine the progression-free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158. The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2-tier system. The association of tumor grade with PFS and OS was assessed. Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2-tier system, patients with low-grade versus high-grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high-grade versus low-grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17-5.04; P = .02). Women with high-grade versus low-grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2-tier grading system provides a simple yet precise framework for predicting clinical outcomes. Copyright © 2011 American Cancer Society.

Can the FIGO 2000 scoring system for gestational trophoblastic neoplasia be simplified? A new retrospective analysis from a nationwide dataset.

PubMed

Eysbouts, Y K; Ottevanger, P B; Massuger, L F A G; IntHout, J; Short, D; Harvey, R; Kaur, B; Sebire, N J; Sarwar, N; Sweep, F C G J; Seckl, M J

2017-08-01

Worldwide introduction of the International Fedaration of Gynaecology and Obstetrics (FIGO) 2000 scoring system has provided an effective means to stratify patients with gestational trophoblastic neoplasia to single- or multi-agent chemotherapy. However, the system is quite elaborate with an extensive set of risk factors. In this study, we re-evaluate all prognostic risk factors involved in the FIGO 2000 scoring system and examine if simplification is feasible. Between January 2003 and December 2012, 813 patients diagnosed with gestational trophoblastic neoplasia were identified at the Trophoblastic Disease Centre in London and scored using the FIGO 2000. Multivariable analysis and stepwise logistic regression were carried out to evaluate whether the FIGO 2000 scoring system could be simplified. Of the eight FIGO risk factors only pre-treatment serum human chorionic gonadotropin (hCG) levels exceeding 10 000 IU/l (OR = 5.0; 95% CI 2.5-10.4) and 100 000 IU/l (OR = 14.3; 95% CI 4.7-44.1), interval exceeding 7 months since antecedent pregnancy (OR = 4.1; 95% CI 1.0-16.2), and tumor size of over 5 cm (OR = 2.2; 95% CI 1.3-3.6) were identified as independently predictive for single-agent resistance. In addition, increased risk was apparent for antecedent term pregnancy (OR = 3.4; 95% CI 0.9-12.7) and the presence of five or more metastases (OR = 3.5; 95% CI 0.4-30.4), but patient numbers in these categories were relatively small. Stepwise logistic regression identified a simplified risk scoring model comprising age, pretreatment serum hCG, number of metastases, antecedent pregnancy, and interval but omitting tumor size, previous failed chemotherapy, and site of metastases. With this model only 1 out 725 patients was classified different from the FIGO 2000 system. Our simplified alternative using only five of the FIGO prognostic factors appears to be an accurate system for discriminating patients requiring single as opposed to multi-agent chemotherapy. Further work is urgently needed to validate these findings. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Histological grading of ovarian clear cell adenocarcinoma: proposal for a simple and reproducible grouping system based on tumor growth architecture.

PubMed

Yamamoto, Sohei; Tsuda, Hitoshi; Shimazaki, Hideyuki; Takano, Masashi; Yoshikawa, Tomoyuki; Kuzuya, Kazuo; Tsuda, Hiroshi; Kurachi, Hirohisa; Kigawa, Junzo; Kikuchi, Yoshihiro; Sugiyama, Toru; Matsubara, Osamu

2012-03-01

In this study, we aimed to develop a histological grading system for ovarian clear cell adenocarcinoma (CCA), based on the tumor growth architectures. Cases were defined as Group A if ≥90% of a tumor examined was composed of well-differentiated tubulocystic and/or papillary architectures; Group C if at least 10% of the tumor was composed of very poorly differentiated histology (i.e. solid masses or individual infiltrating tumor cells with no or little glandular/papillary differentiation); and tumors not corresponding to the first 2 descriptions were defined as Group B. The interobserver reproducibility and prognostic value of the assigned groups were analyzed for 159 CCAs from 5 institutions. The level of agreement in assigning the groups between 2 pathologists was 88.7% (=0.82). After consensus was reached, 46 (29%), 79 (50%), and 34 (21%) tumors were classified in Groups A, B, and C, respectively. In early-stage cases [International Federation of Gynecology and Obstetrics (FIGO) stage I-II], Group A tumors had significantly better outcomes (100% 5-yr survival) than Group B tumors (82% 5-yr survival, P=0.024 by log-rank test) or Group C tumors (56% 5-yr survival, P=0.00054 by log-rank test). Moreover, early-stage Group B tumors had significantly better outcomes than Group C tumors (P<0.001 by a generalized Wilcoxon test). In advanced cases (FIGO stage III-IV), Group A tumors had significantly better outcomes than Group C tumors (52% vs. 16% 5-yr survival, respectively, P=0.043). Group A and C tumors defined with our system were identified to have favorable and unfavorable prognostic factors, respectively, independent of the clinical stage of the disease and presence of residual tumors after the initial surgery. The proposed grouping system could divide patients with CCA into 3 subgroups with distinct prognostic indications, providing a 3-tier histological grading system for ovarian CCA.

Increased expression of placental growth factor in high-grade endometrial carcinoma

PubMed Central

COENEGRACHTS, LIEVE; SCHRAUWEN, STEFANIE; VAN BREE, RITA; DESPIERRE, EVELYN; LUYTEN, CATHERINE; JONCKX, BART; STASSEN, JEAN MARIE; VERGOTE, IGNACE; AMANT, FRÉDÉRIC

2013-01-01

Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models. In the present study, we evaluated the diagnostic and prognostic value of systemic and local expression of PlGF in primary endometrial carcinomas. PlGF levels in tumor lysates (n=128) and serum (n=88) of patients with primary endometrial cancer were determined using ELISA. PlGF mRNA expression in endometrial carcinoma tissues was quantified by quantitative qRT-PCR. Results were compared to endometrial cancer stage and grade. Systemic PlGF levels were not altered in patients with endometrial cancer (FIGO stage I-II-III) as compared to healthy controls. Only in FIGO stage IV patients, serum PlGF levels were slightly increased. Local PlGF mRNA and protein expression in endometrial tumors progressively increased with tumor grade. In endometrioid carcinomas, PlGF mRNA expression was significantly increased in endometrioid grade 3 tumors as compared to normal endometrial tissue. PlGF protein expression was significantly increased in endometrioid grade 2 and 3 carcinomas and in serous carcinomas as compared to normal endometrial tissue. Our study showed that systemic/serum PlGF levels cannot be used as a diagnostic or prognostic marker in endometrial cancer. However, the increased local expression of PlGF, primarily in high-grade carcinomas, underscores the possibility for preclinical assessment of anti-PlGF therapy in endometrial cancer. PMID:23232836

Increased expression of placental growth factor in high-grade endometrial carcinoma.

PubMed

Coenegrachts, Lieve; Schrauwen, Stefanie; Van Bree, Rita; Despierre, Evelyn; Luyten, Catherine; Jonckx, Bart; Stassen, Jean Marie; Vergote, Ignace; Amant, Frédéric

2013-02-01

Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models. In the present study, we evaluated the diagnostic and prognostic value of systemic and local expression of PlGF in primary endometrial carcinomas. PlGF levels in tumor lysates (n=128) and serum (n=88) of patients with primary endometrial cancer were determined using ELISA. PlGF mRNA expression in endometrial carcinoma tissues was quantified by quantitative qRT-PCR. Results were compared to endometrial cancer stage and grade. Systemic PlGF levels were not altered in patients with endometrial cancer (FIGO stage I-II-III) as compared to healthy controls. Only in FIGO stage IV patients, serum PlGF levels were slightly increased. Local PlGF mRNA and protein expression in endometrial tumors progressively increased with tumor grade. In endometrioid carcinomas, PlGF mRNA expression was significantly increased in endometrioid grade 3 tumors as compared to normal endometrial tissue. PlGF protein expression was significantly increased in endometrioid grade 2 and 3 carcinomas and in serous carcinomas as compared to normal endometrial tissue. Our study showed that systemic/serum PlGF levels cannot be used as a diagnostic or prognostic marker in endometrial cancer. However, the increased local expression of PlGF, primarily in high-grade carcinomas, underscores the possibility for preclinical assessment of anti-PlGF therapy in endometrial cancer.

Diagnostic Accuracy of MRI, DWI MRI, FDG-PET/CT and FEC PET/CT in the Detection of Lymph Node Metastases in Surgically Staged Endometrial and Cervical Carcinoma

ClinicalTrials.gov

2017-08-30

Surgically Staged Endometrial and Cervical Carcinoma; Cervical Cancer: Invasive Disease, FIGO Stage 1B1 or Higher; Endometrial Cancer; Stage 1A With Myometrial Invasion or Any Higher Stage and Grade 3; Stage 1A With Myometrial Invasion or Any Other Higher Stage and Serous Papillary or Clear Cell Sub-types; Stage II Disease or Above and Any Histology Grade

Recurrence patterns and survival endpoints in women with stage II uterine endometrioid carcinoma: a multi-institution study.

PubMed

Elshaikh, Mohamed A; Al-Wahab, Zaid; Mahdi, Haider; Albuquerque, Kevin; Mahan, Meredith; Kehoe, Siobhan M; Ali-Fehmi, Rouba; Rose, Peter G; Munkarah, Adnan R

2015-02-01

There is paucity of data in regard to prognostic factors and outcome of women with 2009 FIGO stage II disease. The objective of this study was to investigate prognostic factors, recurrence patterns and survival endpoints in this group of patients. Data from four academic institutions were analyzed. 130 women were identified with 2009 FIGO stage II. All patients underwent hysterectomy, oophorectomy and lymph node evaluation with or without pelvic and paraaortic lymph node dissections and peritoneal cytology. The Kaplan-Meier approach and Cox regression analysis were used to estimate recurrence-free (RFS), disease-specific (DSS) and overall survival (OS). Median follow-up was 44months. 120 patients (92%) underwent simple hysterectomy, 78% had lymph node dissection and 95% had peritoneal cytology examination. 99 patients (76%) received adjuvant radiation treatment (RT). 5-year RFS, DSS and OS were 77%, 90%, and 72%, respectively. On multivariate analysis of RFS, adjuvant RT, the presence of lymphovascular space invasion (LVSI) and high tumor grades were significant predictors. For DSS, LVSI and high tumor grades were significant predictors while older age and high tumor grade were the only predictors of OS. In this multi-institutional study, disease-specific survival for women with FIGO stage II uterine endometrioid carcinoma is excellent. High tumor grade, lymphovascular space invasion, adjuvant radiation treatment and old age are important prognostic factors. There was no significant difference in the outcome between patients who received vaginal cuff brachytherapy compared to those who received pelvic external beam radiation treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.

PubMed

Sood, S; Patel, F D; Ghosh, S; Arora, A; Dhaliwal, L K; Srinivasan, R

2015-12-01

Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Abridged republication of FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum.

PubMed

Prat, Jaime

2015-10-01

Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture ("surgical spill") is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB). © 2015 American Cancer Society.

Radiation therapy in primary carcinoma of the vagina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, S.; Lee, M.S.; Graham, J.E.

1987-01-01

A retrospective analysis of 32 patients with carcinoma of the vagina treated with curative radiotherapy between 1965 and 1981 is presented. Squamous cell carcinoma was the most common histologic type, found in 78% of the patients. Patients were staged according to the FIGO system. Stage I and II disease was found in 8 and 18 patients, respectively. Six patients had either Stage III or IV disease. The absolute survival rate was 100% for Stage I and 72% for Stage II patients. The pattern of failure was analyzed. All patients who failed had done so within 14 months of completion ofmore » treatment. Treatment failure in the pelvis occurred only in 16% of the patients with early disease (Stages I and II) while 81% of the patients with late stage had failed in the pelvis.« less

Cancer of the ovary, fallopian tube, and peritoneum: a population-based comparison of the prognostic factors and outcomes.

PubMed

Rottmann, Miriam; Burges, A; Mahner, S; Anthuber, C; Beck, T; Grab, D; Schnelzer, A; Kiechle, M; Mayr, D; Pölcher, M; Schubert-Fritschle, G; Engel, J

2017-09-01

The objective was to compare the prognostic factors and outcomes among primary ovarian cancer (OC), fallopian tube cancer (FC), and peritoneal cancer (PC) patients in a population-based setting. We analysed 5399 OC, 327 FC, and 416 PC patients diagnosed between 1998 and 2014 in the catchment area of the Munich Cancer Registry (meanwhile 4.8 million inhabitants). Tumour site differences were examined by comparing prognostic factors, treatments, the time to progression, and survival. The effect of the tumour site was additionally analysed by a Cox regression model. The median age at diagnosis, histology, and FIGO stage significantly differed among the tumour sites (p < 0.001); PC patients were older, more often diagnosed with a serous subtype, and in FIGO stage III or IV. The time to progression and survival significantly differed among the tumour sites. When stratified by FIGO stage, the differences in time to progression disappeared, and the differences in survival considerably weakened. The differences in the multivariate survival analysis showed an almost identical outcome in PC patients (HR 1.07 [0.91-1.25]) and an improved survival of FC patients (HR 0.63 [0.49-0.81]) compared to that of OC patients. The comparison of OC, FC, and PC patients in this large-scale population-based study showed differences in the prognostic factors. These differences primarily account for the inferior outcome of PC patients, and for the improved survival of FC compared to OC patients.

Integrated care in ovarian cancer “IgV Ovar”: results of a German pilot for higher quality in treatment of ovarian cancer.

PubMed

Keyver-Paik, M-D; Abramian, A; Domröse, C; Döser, A; Höller, T; Friedrich, M; Meier, W; Menn, K; Kuhn, W

2016-02-01

Late-stage ovarian cancer patient's survival depends on complete cytoreduction and chemotherapy. Complete cytoreduction is more often achieved in institutions with a case volume of >20 cases per year. The Integrated care program Ovar (IgV Ovar) was founded in 2005 and started recruiting in 2006 with 21 health insurances and six expert centers of ovarian cancer treatment as a quality initiative. Results of the pilot and outcomes of patients of three participating centers will be presented here. Data of 1038 patients with ovarian cancer were collected. Adjuvant patients (n = 505) stage FIGO IIB-IV (n = 307) were analyzed for cytoreduction and survival. FIGO IIIC patients were analyzed separately. Median follow-up was 32.7 months. Progression-free survival (PFS) was 23.1 months and overall survival (OS) was 53.6 months for stage IIB-IV. Patients with FIGO IIIC were completely cytoreduced in 48 %. PFS was 21, 29 months if completely cytoreduced. OS was 47.4, 64.9 months if completely cytoreduced.D ISCUSSION: Although the IgV Ovar Rhineland proved to have some structural problems with recruitment and prospective data collection, cytoreduction rates and outcome of patients prove treatment of patients in expert centers is superior to the national and international mean. Therefore, a new quality initiative will be started to bring more awareness to women and to their gynecologists and general practitioners of just how important a good referral strategy is.

Prophylactic lower para-aortic irradiation using intensity-modulated radiotherapy mitigates the risk of para-aortic recurrence in locally advanced cervical cancer: A 10-year institutional experience.

PubMed

Lee, Jie; Lin, Jhen-Bin; Chang, Chih-Long; Jan, Ya-Ting; Sun, Fang-Ju; Wu, Meng-Hao; Chen, Yu-Jen

2017-07-01

To evaluate the effects of prophylactic sub-renal vein radiotherapy (SRVRT) using intensity-modulated radiotherapy (IMRT) for cervical cancer. A total of 206 patients with FIGO stage IB2-IVA cervical cancer and negative para-aortic lymph nodes (PALNs) who underwent pelvic IMRT (PRT) or SRVRT between 2004 and 2013 at our institution were reviewed. SRVRT cranially extended the PRT field for PALNs up to the left renal vein level. The prescribed dose was consistent 50.4Gy in 28 fractions. Overall, 110 and 96 patients underwent PRT and SRVRT, respectively. The SRVRT group had more advanced disease based on FIGO stage and positive pelvic lymph nodes (PLNs). The median follow-up time was 60months (range, 7-143). For the total study population, the 5-year PALN recurrence-free survival (PARFS) and overall survival (OS) for PRT vs. SRVRT were 87.6% vs. 97.9% (p=0.03) and 74.5% vs. 87.8% (p=0.04), respectively. In patients with FIGO III-IVA or positive PLNs, the 5-year PARFS and OS for PRT vs. SRVRT were 80.1% vs. 96.4% (p=0.02) and 58.1% vs. 83.5% (p=0.012), respectively. However, there were no significant differences in these outcomes for patients with FIGO IB-IIB and negative PLNs. In a multivariate analysis, only SRVRT was associated with better PARFS (HR, 0.21; 95% CI, 0.06-0.78; p=0.02). The SRVRT did not significantly increase severe late toxicities. Prophylactic SRVRT using IMRT reduced PALN recurrence with tolerable toxicities, supporting the application of risk-based radiation fields for cervical cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative study of LDR (Manchester system) and HDR image-guided conformal brachytherapy of cervical cancer: patterns of failure, late complications, and survival.

PubMed

Narayan, Kailash; van Dyk, Sylvia; Bernshaw, David; Rajasooriyar, Chrishanthi; Kondalsamy-Chennakesavan, Srinivas

2009-08-01

To compare patterns of failure, late toxicities, and survival in locally advanced cervical cancer patients treated by either low-dose-rate (LDR) or conformal high-dose-rate (HDRc) brachytherapy as a part of curative radiotherapy. A retrospective comparative study of 217 advanced cervix cancer patients was conducted; 90 of these patients received LDR and 127 received HDRc brachytherapy. All patients were staged using International Federation of Gynecology and Obstetrics (FIGO) rules, had pretreatment magnetic resonance imaging (MRI), and were treated with concurrent cisplatin chemoradiotherapy. Both groups matched for FIGO stage, MRI tumor volume, and uterine invasion status. Local and pelvic failures were similar 12-13% and 14% both in both groups. Abdominal and systemic failures in LDR group were 21% and 24%, whereas corresponding failures in HDRc group were 20% and 24%. Sixty-eight percent (87/127) of patients treated by HDRc remained asymptomatic, whereas 42% (38/90) of patients were asymptomatic from the bowel and bladder symptoms after treatment with LDR. The 5-year OS rate was 60% (SE = 4%). The 5-year failure-free survival rate was 55% (SE = 3%). There was no significant difference between the groups. Image-guided HDRc planning led to a large decrease in late radiation effects in patients treated by HDRc. Patterns of failure and survival were similar in patients treated either by LDR or HDRc.

Expression of protease-activated receptor-2 (PAR-2) is related to advanced clinical stage and adverse prognosis in ovarian clear cell carcinoma.

PubMed

Aman, Murasaki; Ohishi, Yoshihiro; Imamura, Hiroko; Shinozaki, Tomoko; Yasutake, Nobuko; Kato, Kiyoko; Oda, Yoshinao

2017-06-01

Recent studies demonstrated that protease-activated receptor-2 (PAR-2) correlates with tumor progression in various tissues. On the other hand, oxidative stress arising from endometriosis has been considered a cause of carcinogenesis in ovarian clear cell carcinoma (OCCC). We previously demonstrated that oxidative stress up-regulates PAR-2 expression, and we conducted the present study to investigate the PAR-2 expression and its relation to clinicopathological factors and oxidative stress in OCCC. We performed an immunohistochemical evaluation in 95 cases of OCCC. For the evaluation of oxidative stress markers, 31 cases of ovarian endometrioid carcinoma (OEC) were also examined. No significant differences in the expression of cyclooxygenase-2 and inducible nitric oxide synthase were observed between OCCC and OEC. Sixty-two percent of the OCCC cases showed high 8-hydroxydeoxyguanosine expression, whereas all of the OEC cases showed almost negative immunoreactivities. The presence of endometriosis did not affect the expression of these oxidative stress markers or prognosis. High PAR-2 expression was observed in 20% (14/71) of the early International Federation of Gynecology and Obstetrics (FIGO) stage cases and 58% (14/24) of the advanced FIGO stage cases. High PAR-2 expression was significantly correlated with advanced FIGO stage and shorter overall survival. We found no correlations between PAR-2 expression and oxidative stress in OCCC. Our results suggest that PAR-2 plays an important role in the progression of OCCC. The expression of 8-hydroxydeoxyguanosine is a characteristic finding of OCCC, indicating that the injury of DNA by oxidative stress may be involved in the carcinogenesis of OCCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Revised FIGO staging system for cancer of the ovary, fallopian tube, and peritoneum: important implications for radiologists.

PubMed

Saida, Tsukasa; Tanaka, Yumiko Oishi; Matsumoto, Koji; Satoh, Toyomi; Yoshikawa, Hiroyuki; Minami, Manabu

2016-02-01

Ovarian cancer is the seventh most common cancer diagnosis among women worldwide. The International Federation of Gynecology and Obstetrics recently significantly revised staging criteria for cancer of the ovary. The latest revision was based on the concept that high-grade serous tubal intraepithelial carcinoma (STIC) may be the origin of some high-grade serous carcinomas of the ovary and peritoneum. Therefore, staging criteria for the ovary, fallopian tube, and peritoneum have been unified. Understanding this background and other important revised points are essential for radiologists concerned with imaging diagnosis in gynecologic oncology. Through this review, we introduce the STIC theory and show examples of diseases in accordance with the new staging criteria based on magnetic resonance imaging (MRI) and computed tomography (CT) results.

[Therapeutic outcomes in patients with cervical cancer FIGO stage IB1].

PubMed

Kornovski, Y; Ismail, E; Kaneva, M

2012-01-01

To establish overall and disease-free survival (OS and DFS) for patients with FIGO IB1 stage cervical cancer for median period of follow-up of 41 months. Between 11.2002-11.2011 110 women with histologically confirmed cervical cancer IB1 stage were operated on by the author. Surgery was radical hysterectomy class III (Piver) and pelvic lymphonodulectomy (ovariectomy was optionally). 76 patients were submitted to adjuvant RT (TGT- 52 - 54 Gy). The period of follow-up ranges from 2 to 104 monts, median 41 monts. The acturial OS and DFS in patients with cervical cancer IB1 stage were estimated as 90% and 90.9%, respectively. Eleven patients had died for the period of follow-up and in 10 occurred local or distant recurrences. The time to develop recurrences was estimated as 16.81 months. Four patients developed local recurrences and six--distant metastases. Surgical and combined therapy of cervical cancer patients IB1 stage leads to high rate OS and DFS--90% and 90.9%, respectively. The incidence rate of distant metastases (5.5%)--in six patients in this stage makes pelvic lymph node dissection crucial and the presence of LM in gluteal and presacral lymph nodes requires paraaortic lymph node dissection.

Lymph-vascular space involvement and outer one-third myometrial invasion are strong predictors of distant haematogeneous failures in patients with stage I-II endometrioid-type endometrial cancer.

PubMed

Gadducci, Angiolo; Cavazzana, Andrea; Cosio, Stefania; DI Cristofano, Claudio; Tana, Roberta; Fanucchi, Antonio; Teti, Giancarlo; Cristofani, Renza; Genazzani, Andrea Riccardo

2009-05-01

The aim of this retrospective study was to assess the predictive value of different clinicopathological variables (patient age, tumour size, FIGO grade, myometrial invasion, lymph-vascular space involvement [LVSI], invasion margins, peri-tumour phlogistic infiltrate and mitotic activity) for the risk of distant haematogenous recurrences in patients with endometrioid-type stage Ib-II endometrial cancer. Between August 1990 and April 2005, 259 patients had undergone laparotomy, peritoneal washing, total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without pelvic +/- para-aortic lymphadenectomy for endometrioid-type endometrial cancer. Thirty-six (13.9%) patients had developed recurrent disease after a median time of 17 months (range, 2-128 months). The relapse had been locoregional in 9, distant in 21 and both locoregional plus distant in 6 cases. This study assessed 12 patients with FIGO stage Ib-II disease who had developed distant haematogenous recurrences and 20 randomly chosen control patients with FIGO stage Ib-II disease who had remained recurrence-free after a median follow-up of 52 months (range, 37-66 months). Adjuvant therapy had been: no further treatment in 15 patients, external pelvic irradiation in 14 patients, adjuvant external pelvic irradiation plus brachytherapy in 2 patients and platinum-based chemotherapy followed by external pelvic irradiation in 1 patient. The site of distant failure had been the lung in 9 patients, liver in 2 patients and lung plus liver in 1 patient. A concomitant locoregional relapse (vagina or lymph nodes) had occurred in 3 patients. The median interval between surgery and the development of distant failure had been 16.5 months (range, 5-113 months). On univariate analysis, a higher incidence of FIGO grade 3 (50% versus 10%, p=0.0114), outer one-third myometrial invasion (91.7% versus 35.0%, p=0.0051) and LVSI (75.0.% versus 20.0%, p=0.0022) was found in the patients who had developed distant haematogeneous metastases compared to the recurrence-free women. Multivariate analysis showed that LVSI (p=0.0264) and deep myometrial invasion (p=0.0345) were independent predictive variables for the risk of distant haematogeneous failure. Patients with these pathological findings should be enrolled in randomised trials designed to assess the role of adjuvant chemotherapy alone or combined with sequential and/or concomitant external pelvic irradiation.

Cervical Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Cervical cancer treatment modalities include surgery, radiation therapy, chemotherapy and targeted therapy. They may be used alone or in combination depending on tumor volume, spread pattern, and FIGO staging. Get detailed information about cervical cancer treatment in this summary for clinicians.

Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

NASA Astrophysics Data System (ADS)

Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

2017-08-01

To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p < 0.2). In the definitive radiation group, overall survival at years one, two, and three were 96%, 92%, and 92%, respectively. A hemoglobin (Hb) level >12 g/dl was a factor with an average association with the overall survival (p < 0.2). The differences between both groups of therapy were not statistically significant (92% vs. 93.3%; p = 0.138). This study did not show any statistically significant overall survival for cervical cancer FIGO stage IB-IIA patients who received definitive radiation or adjuvant postoperative radiation. Negative lymph node metastasis had an effect on the overall survival rate in the adjuvant postoperative radiation group, while a preradiation Hb level >12 g/dl tended to affect the overall survival in the definitive radiation group patients.

The inflammation-based Glasgow Prognostic Score predicts survival in patients with cervical cancer.

PubMed

Polterauer, Stephan; Grimm, Christoph; Seebacher, Veronika; Rahhal, Jasmin; Tempfer, Clemens; Reinthaller, Alexander; Hefler, Lukas

2010-08-01

The Glasgow Prognostic Score (GPS) is known to reflect the degree of tumor-associated cachexia and inflammation and is associated with survival in various malignancies. We investigated the value of the GPS in patients with cervical cancer. We included 244 consecutive patients with cervical cancer in our study. The pretherapeutic GPS was calculated as follows: patients with elevated C-reactive protein serum levels (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2, and patients with 1 or no abnormal value were allocated a score of 1 or 0, respectively. The association between GPS and survival was evaluated by univariate log-rank tests and multivariate Cox regression models. The GPS was correlated with clinicopathologic parameters as shown by performing chi2 tests. In univariate analyses, GPS (P < 0.001, P < 0.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001, P < 0.001), and lymph node involvement (P < 0.001, P < 0.001), but not patients' age (P = 0.2, P = 0.07), histological grade (P = 0.08, P = 0.1), and histological type (P = 0.8, P = 0.9), were associated with disease-free and overall survival, respectively. In a multivariate analysis GPS (P = 0.03, P = 0.04), FIGO stage (P = 0.006, P = 0.006), and lymph node involvement (P = 0.003, P = 0.002), but not patients' age (P = 0.5, P = 0.5), histological grade (P = 0.7, P = 0.6), and histological type (P = 0.4, P = 0.6) were associated with disease-free and overall survival, respectively. The GPS was associated with FIGO stage (P < 0.001) and histological grade (P = 0.02). The GPS can be used as an inflammation-based predictor for survival in patients with cervical cancer.

Adjuvant chemotherapy in patients with stage I endometrioid or clear cell ovarian cancer in the platinum era: a Surveillance, Epidemiology, and End Results Cohort Study, 2000-2013.

PubMed

Oseledchyk, A; Leitao, M M; Konner, J; O'Cearbhaill, R E; Zamarin, D; Sonoda, Y; Gardner, G J; Long Roche, K; Aghajanian, C A; Grisham, R N; Brown, C L; Snyder, A; Chi, D S; Soslow, R A; Abu-Rustum, N R; Zivanovic, O

2017-12-01

We sought to evaluate the impact of adjuvant chemotherapy on overall survival (OS) in patients with stage I endometrioid epithelial ovarian cancer (EEOC) or ovarian clear cell cancer (OCCC) using a national database. The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I EEOC or OCCC from 2000 to 2013. We sought to identify predictors of chemotherapy use and to assess the impact of chemotherapy on OS in these patients. OS was compared using the log-rank test and the Cox proportional hazards model. In all, 3552 patients with FIGO stage I EEOC and 1995 patients with stage I OCCC were identified. Of the 1600 patients (45%) with EEOC who underwent adjuvant chemotherapy, the 5-year OS rate was 90%, compared with 89% for those who did not undergo adjuvant chemotherapy (P = 0.807). Of the 1374 (69%) patients with OCCC who underwent adjuvant chemotherapy, the 5-year OS rate was 85%, compared with 83% (P = 0.439) for those who did not undergo adjuvant chemotherapy. Chemotherapy use was associated with younger age, higher substage, and more recent year of diagnosis for both the EEOC and OCCC groups. Only in the subgroup of patients with FIGO substage IC, grade 3 EEOC (n = 282) was chemotherapy associated with an improved 5-year OS-81% compared with 62% (P = 0.003) in untreated patients (HR: 0.583; 95% CI: 0.359-0.949; P = 0.030). In patients with OCCC, there was no significant effect of adjuvant chemotherapy on OS in any substage. Adjuvant chemotherapy was associated with improved OS only in patients with substage IC, grade 3 EEOC. In stage I OCCC, adjuvant chemotherapy was not associated with improved OS. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Computed Tomography–Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zolciak-Siwinska, Agnieszka, E-mail: agnieszka.zolciak@wp.pl; Gruszczynska, Ewelina; Bijok, Michal

Purpose: To evaluate the long-term results of computed tomography (CT)–planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. Methods and Materials: CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective,more » Management, Analysis evaluation scoring system and compared them with the results from a historical group. Results: The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. Conclusions: This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and acceptable toxicity. In comparison with the historical series, there is a substantial benefit in terms of severe late effects. FIGO III and enlarged lymph nodes in positron emission tomography–CT/CT are negative prognostic factors, both with a relative risk of failure of approximately 2.« less

[Sentinel node detection in early stage of cervical carcinoma using 99mTc-nanocolloid and blue dye].

PubMed

Sevcík, L; Klát, J; Gráf, P; Koliba, P; Curík, R; Kraft, O

2007-04-01

The aim of the study was to analyse the feasibility of intraoperative sentinel lymph nodes (SLN) detection using gamma detection probe and blue dye in patients undergoing radical hysterectomy for treatment of early stage of cervical cancer. Prospective case observational study. In the period from May 2004 to February 2006 77 patients with early stage of cervical cancer who underwent a radical surgery were included into the study. Patients were divided into three groups according to the tumour volume. First group consists of patients FIGO IA2 and FIGO IB1 with tumour diameter less than 2 cm, second group tumours FIGO IB1 with tumour diameter more than 2 cm and third group stadium IB2. SLN was detected by blue dye and Tc99. Preoperative lymphoscintigraphy was done after Tc99 colloid injection, intraoperative detection was performed by visual observation and by hand-held gamma-detection probe. SLN were histologically and immunohistochemically analysed. A total number of 2764 lymph nodes with an average 36 and 202 SLN with an average 2.6 were identified. The SLN detection rate was 94.8% per patient and 85.1% for the side of dissection and depends on the tumor volume. SLN were identified in obturator area in 48%, in external iliac area in 15%, in common iliac and internal iliac both in 9%, in interiliac region in 8%, in praesacral region in 6% and in parametrial area in 5%. Metastatic disease was detected in 31 patients (40.2%), metastatic involvement of SLN only in 12 patients (15.6%). False negative rate was 2.6%, sensitivity and negative predictive value calculated by patient were 923% and 95.7%. Intraoperative lymphatic mapping using combination of technecium-99-labeled nanocolloid and blue dye are feasible, safe and accurate techniques to identified SLN in early stage of cervical cancer.

Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation.

PubMed

Huang, Hsien-Neng; Chiang, Ying-Cheng; Cheng, Wen-Fang; Chen, Chi-An; Lin, Ming-Chieh; Kuo, Kuan-Ting

2015-02-01

Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (P<0.001), preserved ARID1A immunoreactivity (P=0.017) and infrequent PIK3CA mutation (P=0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age >45 (P=0.045) and preserved ARID1A expression (P=0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P=0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P=0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy.

[Results of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years from 1993 to 2012].

PubMed

Korbeľ, M; Šufliarsky, J; Danihel, Ľ; Vojtaššák, J; Nižňanská, Z

2016-01-01

Analysis and epidemiology of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years 1993-2012. Retrospective epidemiological national study. Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic, Bratislava. Retrospective analysis results of gestational trophoblastic neoplasia treatment according to prognostic scoring and staging system FIGO/WHO in Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic Bratislava in the years 1993-2012. The treatment of gestational trophoblastic neoplasia (GTN) in the Czech and Slovak Republics started in 1955 and lasted till 1993. After the split of the former Czechoslovakia the Centre for gestational trophoblastic disease was created in Slovakia. 75 patients were treated in this Centre in the years 1993-2012. According to prognostic scoring and staging system FIGO/WHO 56 (75%) patients had low-risk gestational trophoblastic neoplasia and 19 (25%) of patients had high-risk gestational trophoblastic neoplasia. There were 41 patients (55%), 2 (3%), 24 (32%) and 8 (11%) in stage I., II., III. and IV. respectively. Total curability rate was 94.7% and mortality rate was 5.3%. Curability rate 100% was achieved in stage I & II and all placental site trophoblastic tumours (PSTT), 98.3% in stage III and 50% stage IV. In the years 1993-2012 the incidence of choriocarcinoma was one in 76 273 pregnancies and one in 53 203 deliveries. The incidence of other gestational trophoblastic neoplasia in the same years was for PSTT one in 533 753 pregnancies and one in 372 422 deliveries, invasive mole one in 145 611 pregnancies and one in 101 569 deliveries, and persistent GTN one in 40 043 pregnancies and one in 27 932 deliveries. 225-241 patients were treated in the same period of time in the Czech Republic with curability rate 98.2-98. 3%. Early detection and treatment in the centre for trophoblastic disease are crucial points in the manage-ment of gestational trophoblastic neoplasia, because the effective therapy of gestational trophoblastic neoplasia with high curability rate is available.

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Extracapsular extension of pelvic lymph node metastases is of prognostic value in carcinoma of the cervix uteri.

PubMed

Horn, Lars-Christian; Hentschel, Bettina; Galle, Dana; Bilek, Karl

2008-01-01

Pelvic lymph node involvement is a well-recognized prognostic factor in cervical carcinoma (CX). Limited knowledge exists about extranodal extension of the tumor outside the lymph node capsule, i.e. extracapsular spread (ECS). Two hundred fifty-six cases of surgically treated CX (FIGO stage IB1 to IIB) with pelvic lymph node involvement were evaluated regarding the occurrence of extranodal spread of the metastatic deposits outside the lymph node capsule (ECS), determined on standardized handled lymphadenectomy specimens, regarding their impact of recurrent disease and overall survival during a median follow-up time of 62 months (95% CI 51-73 months). ECS was seen in 30.9% (79/256) of the cases. The occurrence of ECS showed a significant correlation to advanced stage disease (p=0.02), the number of involved nodes (p<0.001) and the size of metastatic deposits (p<0.01). The 5-year recurrence-free survival rate in patients with ECS was significant lower compared to patients without ECS (59.7% [95% CI: 46.3%-73.2%] versus 67.2% [95% CI: 58.9%-75.5%]; (p=0.04). The 5-year overall survival rate was significant lower in patients with ECS (33.5% [95% CI: 20.6%-46.3%] vs. 60.5% [95% CI: 52.3%-68.6%]; p<0.001). In multivariate analysis, tumor stage, number of involved pelvic nodes, tumor differentiation and ECS were independent prognostic factors. The results indicate that extracapsular spread (ECS) of pelvic lymph node metastases is of prognostic impact in cervical carcinomas. A revised FIGO/TNM classification system for pelvic lymph node disease is recommended: ECS 0 = lymph node involvement without extranodal spread of the metastatic deposits and ECS 1 = lymph node involvement with extranodal spread of the metastatic deposits.

A preoperative low cancer antigen 125 level (≤25.8 mg/dl) is a useful criterion to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in epithelial ovarian cancer.

PubMed

Morimoto, Akemi; Nagao, Shoji; Kogiku, Ai; Yamamoto, Kasumi; Miwa, Maiko; Wakahashi, Senn; Ichida, Kotaro; Sudo, Tamotsu; Yamaguchi, Satoshi; Fujiwara, Kiyoshi

2016-06-01

The purpose of this study is to investigate the clinical characteristics to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer. We reviewed the charts of women with advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer who underwent interval debulking surgery following neoadjuvant chemotherapy at our cancer center from April 2006 to April 2014. There were 139 patients, including 91 with ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) Stage IIIc in 56 and IV in 35], two with fallopian tube cancers (FIGO Stage IV, both) and 46 with primary peritoneal cancer (FIGO Stage IIIc in 27 and IV in 19). After 3-6 cycles (median, 4 cycles) of platinum-based chemotherapy, interval debulking surgery was performed. Sixty-seven patients (48.2%) achieved complete resection of all macroscopic disease, while 72 did not. More patients with cancer antigen 125 levels ≤25.8 mg/dl at pre-interval debulking surgery achieved complete resection than those with higher cancer antigen 125 levels (84.7 vs. 21.3%; P< 0.0001). Patients with no ascites at pre-interval debulking surgery also achieved a higher complete resection rate (63.5 vs. 34.1%; P< 0.0001). Moreover, most patients (86.7%) with cancer antigen 125 levels ≤25.8 mg/dl and no ascites at pre-interval debulking surgery achieved complete resection. A low cancer antigen 125 level of ≤25.8 mg/dl and the absence of ascites at pre-interval debulking surgery are major predictive factors for complete resection during interval debulking surgery and present useful criteria to determine the optimal timing of interval debulking surgery. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessment of Parametrial Response by Growth Pattern in Patients With International Federation of Gynecology and Obstetrics Stage IIB and IIIB Cervical Cancer: Analysis of Patients From a Prospective, Multicenter Trial (EMBRACE)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshida, Kenji; Kobe University Graduate School of Medicine, Kobe; Jastaniyah, Noha

Purpose: To assess disease response along the parametrial space according to tumor morphology in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and IIIB cervical cancer at the time of image-guided adaptive brachytherapy. Methods and Materials: Patients with FIGO stage IIB and IIIB cervical cancer registered as of November 2013 in the EMBRACE study were evaluated. Tumors were stratified according to morphologic subtype on magnetic resonance imaging (expansive and infiltrative), and the characteristics of those subtypes were analyzed. Parametrial involvement at diagnosis and at brachytherapy was evaluated, and the response to chemo-radiotherapy was classified as good, moderate,more » or poor. The response grade was compared between the 2 groups and analyzed with regard to tumor volumes, and dosimetric parameters. Results: A total of 452 patients were evaluated, of whom 186 had expansive growth type and 266 had infiltrative morphology. Patients with infiltrative tumors had more extensive disease, as indicated by a higher rate of FIGO stage IIIB disease, as well as radiologic evidence of extension into the distal parametrial space and to the pelvic side wall on magnetic resonance imaging. Cervical necrosis was more common in the infiltrative group. Good response was more common in the expansive group (34% vs 24%; P=.02), and poor response was more common in the infiltrative group (11% and 19%; P=.02). Mean gross tumor volume at diagnosis was equal in both groups (51.7 cm{sup 3}). The high-risk clinical target volume was larger in infiltrative tumors (37.9 cm{sup 3} vs 33.3 cm{sup 3}, P=.005). The mean high-risk clinical target volume D{sub 90} was slightly higher in expansive tumors (92.7 Gy and 89.4 Gy, P<.001). Conclusion: Infiltrative tumors are more advanced at presentation and respond less favorably to chemo-radiotherapy when compared with expansive tumors that are more or less equivalent in size. The use of image-guided adaptive brachytherapy allows achieving reasonably high doses in both groups.« less

Gestational trophoblastic neoplasia and human immunodeficiency virus infection: a 10-year review.

PubMed

Tayib, Shahila; van Wijk, Leon; Denny, Lynette

2011-12-01

The objective of the study was to describe the management of gestational trophoblastic neoplasia (GTN), with particular reference to concurrent human immunodeficiency virus (HIV) infection. This retrospective descriptive study comprised all cases of GTN managed at Groote Schuur Hospital over a 10-year period (1999-2008). Seventy-six patients, with a median age of 30 years at presentation, were included in the study. Only 36 patients (47.4%) had known HIV status. Fourteen (18.4%) were HIV positive, and of these, 4 (28.6%) were on antiretroviral treatment (ARV). The mean CD4 count was 142 cells/μL for those on ARV and 543 cells/μL for those not on ARV (P = 0.001). Histologically, 44 patients (58%) had hydatidiform mole, and 21 (28%) had choriocarcinoma. In the remaining 10 cases, a clinical diagnosis was made. Based on the revised International Federation of Gynecology and Obstetrics (FIGO)/modified World Health Organization scoring, 43 patients (56.6%) were low risk, and 33 (43.4%) were high risk. Thirty-eight patients (50%) were staged as FIGO stage I. Of 73 patients who received chemotherapy, 56 (76.7%) achieved complete remission, 9 (12.3%) did not achieve any remission, 7 (9.6%) had a relapse, and 1 (1.4%) was lost to follow-up. Patients who never went into remission had frequent treatment delays due to poor compliance or inadequate blood counts. The overall survival at 60 months was 81.9%. Of the 13 patients (17.1%) who have died, 5 (38.5%) were HIV positive. The overall 5-year survival rates for FIGO stages I, II, III, and IV were 97.4%, 66.7%, 77.8%, and 46.2%, respectively. The overall 5-year survival for HIV-positive patients was 64.3% versus more than 85% for both the HIV-negative and HIV-unknown groups. Apart from more advanced stage, HIV seropositivity and poor compliance with treatment also portend poorer outcome in GTN patients. In HIV-positive patients with poor CD4, little clarity is available whether ARV should be commenced speedily, and the administration of chemotherapy delayed until immune reconstitution occurs.

L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation.

PubMed

Zeimet, Alain G; Reimer, Daniel; Huszar, Monica; Winterhoff, Boris; Puistola, Ulla; Azim, Samira Abdel; Müller-Holzner, Elisabeth; Ben-Arie, Alon; van Kempen, Léon C; Petru, Edgar; Jahn, Stephan; Geels, Yvette P; Massuger, Leon F; Amant, Frédéric; Polterauer, Stephan; Lappi-Blanco, Elisa; Bulten, Johan; Meuter, Alexandra; Tanouye, Staci; Oppelt, Peter; Stroh-Weigert, Monika; Reinthaller, Alexander; Mariani, Andrea; Hackl, Werner; Netzer, Michael; Schirmer, Uwe; Vergote, Ignace; Altevogt, Peter; Marth, Christian; Fogel, Mina

2013-08-07

Despite the excellent prognosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to predict clinical outcome. We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The Kaplan-Meier method and Cox proportional hazard model were applied for survival and multivariable analyses. A machine-learning approach was used to validate variables for predicting recurrence and death. Of 1021 included cancers, 17.7% were rated L1CAM-positive. Of these L1CAM-positive cancers, 51.4% recurred during follow-up compared with 2.9% L1CAM-negative cancers. Patients bearing L1CAM-positive cancers had poorer disease-free and overall survival (two-sided Log-rank P < .001). Multivariable analyses revealed an increase in the likelihood of recurrence (hazard ratio [HR] = 16.33; 95% confidence interval [CI] = 10.55 to 25.28) and death (HR = 15.01; 95% CI = 9.28 to 24.26). In the L1CAM-negative cancers FIGO stage I subdivision, grading and risk assessment were irrelevant for predicting disease-free and overall survival. The prognostic relevance of these parameters was related strictly to L1CAM positivity. A classification and regression decision tree (CRT)identified L1CAM as the best variable for predicting recurrence (sensitivity = 0.74; specificity = 0.91) and death (sensitivity = 0.77; specificity = 0.89). To our knowledge, L1CAM has been shown to be the best-ever published prognostic factor in FIGO stage I, type I endometrial cancers and shows clear superiority over the standardly used multifactor risk score. L1CAM expression in type I cancers indicates the need for adjuvant treatment. This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently under development for clinical use.

Predictive and Prognostic Factors in Definition of Risk Groups in Endometrial Carcinoma

PubMed Central

Sorbe, Bengt

2012-01-01

Background. The aim was to evaluate predictive and prognostic factors in a large consecutive series of endometrial carcinomas and to discuss pre- and postoperative risk groups based on these factors. Material and Methods. In a consecutive series of 4,543 endometrial carcinomas predictive and prognostic factors were analyzed with regard to recurrence rate and survival. The patients were treated with primary surgery and adjuvant radiotherapy. Two preoperative and three postoperative risk groups were defined. DNA ploidy was included in the definitions. Eight predictive or prognostic factors were used in multivariate analyses. Results. The overall recurrence rate of the complete series was 11.4%. Median time to relapse was 19.7 months. In a multivariate logistic regression analysis, FIGO grade, myometrial infiltration, and DNA ploidy were independent and statistically predictive factors with regard to recurrence rate. The 5-year overall survival rate was 73%. Tumor stage was the single most important factor with FIGO grade on the second place. DNA ploidy was also a significant prognostic factor. In the preoperative risk group definitions three factors were used: histology, FIGO grade, and DNA ploidy. Conclusions. DNA ploidy was an important and significant predictive and prognostic factor and should be used both in preoperative and postoperative risk group definitions. PMID:23209924

Value of Magnetic Resonance Imaging Without or With Applicator in Place for Target Definition in Cervix Cancer Brachytherapy.

PubMed

Pötter, Richard; Federico, Mario; Sturdza, Alina; Fotina, Irina; Hegazy, Neamat; Schmid, Maximilian; Kirisits, Christian; Nesvacil, Nicole

2016-03-01

To define, in the setting of cervical cancer, to what extent information from additional pretreatment magnetic resonance imaging (MRI) without the brachytherapy applicator improves conformity of CT-based high-risk clinical target volume (CTVHR) contours, compared with the MRI for various tumor stages (International Federation of Gynecology and Obstetrics [FIGO] stages I-IVA). The CTVHR was contoured in 39 patients with cervical cancer (FIGO stages I-IVA) (1) on CT images based on clinical information (CTVHR-CTClinical) alone; and (2) using an additional MRI before brachytherapy, without the applicator (CTVHR-CTpre-BT MRI). The CT contours were compared with reference contours on MRI with the applicator in place (CTVHR-MRIref). Width, height, thickness, volumes, and topography were analyzed. The CT-MRIref differences hardly varied in stage I tumors (n=8). In limited-volume stage IIB and IIIB tumors (n=19), CTVHR-CTpre-BT MRI-MRIref volume differences (2.6 cm(3) [IIB], 7.3 cm(3) [IIIB]) were superior to CTVHR-CTClinical-MRIref (11.8 cm(3) [IIB], 22.9 cm(3) [IIIB]), owing to significant improvement of height and width (P<.05). In advanced disease (n=12), improved agreement with MR volume, width, and height was achieved for CTVHR-CTpre-BT MRI. In 5 of 12 cases, MRIref contours were partly missed on CT. Pre-BT MRI helps to define CTVHR before BT implantation appropriately, if only CT images with the applicator in place are available for BT planning. Significant improvement is achievable in limited-volume stage IIB and IIIB tumors. In more advanced disease (extensive IIB to IVA), improvement of conformity is possible but may be associated with geographic misses. Limited impact on precision of CTVHR-CT is expected in stage IB tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of hydronephrosis on survival in advanced stage cervical cancer.

PubMed

Goklu, Mehmet Rıfat; Seckin, Kerem Doga; Togrul, Cihan; Goklu, Yasemin; Tahaoglu, Ali Emre; Oz, Murat; Ertas, Ibrahim Egemen

2015-01-01

Hydronephrosis is frequently encountered in advanced stage cervical cancers, and may be associated with mortality. In the present study, we aimed to demonstrate the effect of hydronephrosis on survival in patients with inoperable advanced stage cervical cancer. The study data were acquired by retrospective analysis of the patient records belonging to 165 women with FIGO (International Federation of Gynecology and Obstetrics) stage-IIIB or more advanced cervical cancer, which were not surgical candidates. Parameters including patient age, pathological diagnosis, disease stage, pelvic sidewall extension, presence of hydronephrosis and administration of chemoradiation were analyzed. Further, the effects of these variables on survival were assessed. P values less than 0.05 were considered statistically significant. The distribution of the study patients according to disease stage was as follows: 131 (79.4%) had stage-IIIB, 18 (10.9%) had stage-IVB and 16 (% 9.7) patients had stage-IVA disease. Hydronephrosis was not evident in 91 (55.2%) of these patients, whereas 41 (24.8%) had unilateral and 33 (20%) patients had bilateral hydronephrosis. When compared to mean survival in patients who did not have hydronephrosis, survival was significantly shortened in patients who had bilateral and unilateral hydronephrosis (p<0.05). There was no significant survival difference between patients with unilateral and bilateral hydronephrosis (p>0.05). Although patient age, pathological type, pelvic involvement, and chemotherapy treatment rates were similar (p>0.05), radiotherapy requirement rate and disease stage were significantly different among the study groups (p<0.05). Hydronephrosis was found to be a significant predictor of poor survival in patients with advanced stage cervical cancer, irrespective of unilateral or bilateral involvement.While waiting for future studies with larger sample sizes, we believe that the FIGO stages in advanced cervical cancer could further be stratified into subgroups according to presence or absence of hydronephrosis.

SisPorto 4.0 - computer analysis following the 2015 FIGO Guidelines for intrapartum fetal monitoring.

PubMed

Ayres-de-Campos, Diogo; Rei, Mariana; Nunes, Inês; Sousa, Paulo; Bernardes, João

2017-01-01

SisPorto 4.0 is the most recent version of a program for the computer analysis of cardiotocographic (CTG) signals and ST events, which has been adapted to the 2015 International Federation of Gynaecology and Obstetrics (FIGO) guidelines for intrapartum foetal monitoring. This paper provides a detailed description of the analysis performed by the system, including the signal-processing algorithms involved in identification of basic CTG features and the resulting real-time alerts.

Screening and cervical cancer cure: population based cohort study

PubMed Central

Andersson, Therese M-L; Lambert, Paul C; Kemetli, Levent; Silfverdal, Lena; Strander, Björn; Ryd, Walter; Dillner, Joakim; Törnberg, Sven; Sparén, Pär

2012-01-01

Objective To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death. Design Nationwide population based cohort study. Setting Sweden. Participants All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years. Main outcome measures Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age, histopathological type, and FIGO (International Federation of Gynecology and Obstetrics) stage. Results In the screening ages, the cure proportion for women with screen detected invasive cancer was 92% (95% confidence interval 75% to 98%) and for symptomatic women was 66% (62% to 70%), a statistically significant difference in cure of 26% (16% to 36%). Among symptomatic women, the cure proportion was significantly higher for those who had been screened according to recommendations (interval cancers) than among those overdue for screening: difference in cure 14% (95% confidence interval 6% to 23%). Cure proportions were similar for all histopathological types except small cell carcinomas and were closely related to FIGO stage. A significantly higher cure proportion for screen detected cancers remained after adjustment for stage at diagnosis (difference 15%, 7% to 22%). Conclusions Screening is associated with improved cure of cervical cancer. Confounding cannot be ruled out, but the effect was not attributable to lead time bias and was larger than what is reflected by down-staging. Evaluations of screening programmes should consider the assessment of cure proportions. PMID:22381677

Screening and cervical cancer cure: population based cohort study.

PubMed

Andrae, Bengt; Andersson, Therese M-L; Lambert, Paul C; Kemetli, Levent; Silfverdal, Lena; Strander, Björn; Ryd, Walter; Dillner, Joakim; Törnberg, Sven; Sparén, Pär

2012-03-01

To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death. Nationwide population based cohort study. Sweden. All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years. Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age, histopathological type, and FIGO (International Federation of Gynecology and Obstetrics) stage. In the screening ages, the cure proportion for women with screen detected invasive cancer was 92% (95% confidence interval 75% to 98%) and for symptomatic women was 66% (62% to 70%), a statistically significant difference in cure of 26% (16% to 36%). Among symptomatic women, the cure proportion was significantly higher for those who had been screened according to recommendations (interval cancers) than among those overdue for screening: difference in cure 14% (95% confidence interval 6% to 23%). Cure proportions were similar for all histopathological types except small cell carcinomas and were closely related to FIGO stage. A significantly higher cure proportion for screen detected cancers remained after adjustment for stage at diagnosis (difference 15%, 7% to 22%). Screening is associated with improved cure of cervical cancer. Confounding cannot be ruled out, but the effect was not attributable to lead time bias and was larger than what is reflected by down-staging. Evaluations of screening programmes should consider the assessment of cure proportions.

Ovarian cancer in Lynch syndrome; a systematic review.

PubMed

Helder-Woolderink, J M; Blok, E A; Vasen, H F A; Hollema, H; Mourits, M J; De Bock, G H

2016-03-01

The aim was to systematically review the characteristics of ovarian cancer in women with Lynch syndrome (LS) and evaluate the role of surveillance in detection of ovarian cancer in LS. All studies between 1979 and 2015 of women with ovarian cancer and LS or at 50% risk of LS were evaluated. Two reviewers independently evaluated eligible studies and extracted data on age at diagnosis, histological type, FIGO stage, and way of detection according to pre-specified criteria. The studies were assessed for quality using the Newcastle-Ottawa quality assessment scales. The quality score of the 49 identified studies was at least 6 out of 8 and provide clinical information on 747 LS women with ovarian cancer. The mean age at diagnosis was 45.3 (range 19-82) years. Most frequent mutations were MSH2 (47%) and MLH1 (38%). Histopathological data were available for 445 women. The most frequently reported histological type was mixed type (mucinous/endometrioid/clear cell carcinomas) (n = 136; 31%). Most tumours (281, 65%) were diagnosed at an early stage (FIGO I/II). Six studies evaluating the effect of surveillance of ovarian cancer, reported that seven of 22 (32%) ovarian cancers were found during surveillance, 6/7 (86%) were detected at an early stage. This systematic review describes that ovarian cancer in women with LS has a wide age-range of onset, is often diagnosed at an early stage with frequently endometrioid/clear cell histology. Data about the role of surveillance in detection of ovarian cancer in women with LS are scarce however detection at an early stage seems possible. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sequential versus "sandwich" sequencing of adjuvant chemoradiation for the treatment of stage III uterine endometrioid adenocarcinoma.

PubMed

Lu, Sharon M; Chang-Halpenny, Christine; Hwang-Graziano, Julie

2015-04-01

To compare the efficacy and tolerance of adjuvant chemotherapy and radiotherapy delivered in sequential (chemotherapy followed by radiation) versus "sandwich" fashion (chemotherapy, interval radiation, and remaining chemotherapy) after surgery in patients with FIGO stage III uterine endometrioid adenocarcinoma. From 2004 to 2011, we identified 51 patients treated at our institution fitting the above criteria. All patients received surgical staging followed by adjuvant chemoradiation (external-beam radiation therapy (EBRT) with or without high-dose rate (HDR) vaginal brachytherapy (VB)). Of these, 73% and 27% of patients received their adjuvant therapy in sequential and sandwich fashion, respectively. There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Thirty-nine (76%) patients had stage IIIC disease. The majority of patients received 6 cycles of paclitaxel with carboplatin or cisplatin. Median EBRT dose was 45 Gy and 54% of patients received HDR VB boost (median dose 21 Gy). There were no significant differences in the estimated 5-year overall survival, local progression-free survival, and distant metastasis-free survival between the sequential and sandwich groups: 87% vs. 77% (p=0.37), 89% vs. 100% (p=0.21), and 78% vs. 85% (p=0.79), respectively. No grade 3-4 genitourinary or gastrointestinal toxicities were reported in either group. There was a trend towards higher incidence of grade 3-4 hematologic toxicity in the sandwich group. Adjuvant chemoradiation for FIGO stage III endometrioid uterine cancer given in either sequential or sandwich fashion appears to offer equally excellent early clinical outcomes and acceptably low toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiation therapy for primary squamous cell carcinoma of the vagina: Stanford University experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spirtos, N.M.; Doshi, B.P.; Kapp, D.S.

1989-10-01

A retrospective analysis of 38 patients with primary squamous cell carcinoma of the vagina seen at Stanford University Medical Center from 1958 to 1984 was undertaken. Patients were analyzed with regard to symptoms, stage, treatment techniques, survival, patterns of failure, and complications. Eighteen patients were classified as FIGO Stage I, 5 as Stage II, 10 as Stage III, and 5 as Stage IV. The 5-year disease-free survival was 94% in Stage I, 80% in Stage II, 50% in Stage III, and 0% in Stage IV. Five patients (13%) had eight major complications secondary to treatment. Only 2 of 23 patientsmore » with Stage I or Stage II disease developed a recurrence. There was a significant correlation between dose and response in patients treated with radiotherapy.« less

Conventional 4-field box radiotherapy technique for cancer cervix: potential for geographic miss without CECT scan-based planning.

PubMed

Nagar, Y S; Singh, S; Kumar, S; Lal, P

2004-01-01

The advantage of 4-field radiation to the pelvis is that the use of lateral portals spares a portion of the small bowel anteriorly and rectum posteriorly. The standard lateral portals defined in textbooks are not always adequate especially in advanced cancer cervix. An analysis was done to determine adequacy of margins of standard lateral pelvic portals with CECT defined tumor volumes. The study included 40 patients of FIGO stage IIB and IIIB treated definitively for cancer cervix between 1998 and 2000. An inadequate margin was defined if the cervical growth and uterus were not encompassed by the 95% isodose. An inadequate posterior margin was common with bulky disease (P = 0.06) and with retroverted uterus (P = 0.08). Menopausal status, FIGO stage, associated myoma, and age were of no apparent prognostic significance. Bulk retained significant on multivariate analysis. An inadequate anterior margin was common in premenopausal (P = 0.01); anteverted uterus (P = 0.02); associated myoma (P = 0.01); and younger patients (P = 0.03). It was not influenced by bulk or stage. Menopausal status and associated myoma retained significant on multivariate analysis. Without the knowledge of precise tumor volume, the 4-field technique with standard portals is potentially risky as it may under dose the tumor through lateral portals and the standard AP/ PA portals are a safer option.

[Carcinoma of the uterine cervical canal. Staging and biometric assessment with magnetic resonance].

PubMed

Fischetti, S G; Politi, G; Lomeo, E; Garozzo, G; Di Leo, S; Nuciforo, G

1994-10-01

In uterine cervical canal carcinoma, the current clinical FIGO criteria often fail not only to differentiate stage IA2 from stage IB but also to demonstrate possible parametrial involvement. Moreover, the analysis of tumor volume and of the depth of neoplastic stromal invasion is not very reliable. The authors investigated MR accuracy in the definition of such variables: to this purpose, 24 patients with histologically confirmed endocervical adenocarcinoma were submitted to MRI, which was performed with an 0.5-T superconductive magnet. Sagittal and oblique transverse or sometimes coronal SE images, oriented so as to be perpendicular to longitudinal cervical major axis were obtained with T2 weighting (TR 1800 ms, TE 25-90 ms). MR data were correlated with pathologic findings. MR accuracy in demonstrating parametrial involvement was 92%, its sensitivity was 86% and specificity 97%. Volumetric MR data showed a high correlation (r = 0.970) with those derived from pathologic findings. In 92% of cases stromal invasion exceeded 5 mm. MRI, thanks to its high accuracy, should be included in diagnostic pretreatment protocols, even though FIGO criteria do not require it yet, especially in the presence of an endocervical adenocarcinoma. Moreover, the accurate definition of tumor volume can allow less extensive surgery with the same survival rates and fewer complications, which are frequently observed after radical hysterectomy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chernyshova, A. L.; Lyapunov, A. Yu., E-mail: Lyapunov1720.90@mail.ru; Kolomiets, L. A.

The study included 26 patients with FIGO stage Ia1–Ib1 cervical cancer who underwent fertility-sparing surgery (transabdominaltrachelectomy). To visualize sentinel lymph nodes, lymphoscintigraphy with injection of 99mTc-labelled nanocolloid was performed the day before surgery. Intraoperative identification of sentinel lymph nodes using hand-held gamma probe was carried out to determine the radioactive counts over the draining lymph node basin. The sentinel lymph node detection in cervical cancer patients contributes to the accurate clinical assessment of the pelvic lymph node status, precise staging of the disease and tailoring of surgical treatment to individual patient.

Diagnostic Accuracy of the FIGO and the 5-Tier Fetal Heart Rate Classification Systems in the Detection of Neonatal Acidemia.

PubMed

Martí Gamboa, Sabina; Giménez, Olga Redrado; Mancho, Jara Pascual; Moros, María Lapresta; Sada, Julia Ruiz; Mateo, Sergio Castan

2017-04-01

Objective  The objective of this study was to determine ability to detect neonatal acidemia and interobserver agreement with the FIGO 3-tier and 5-tier fetal heart rate (FHR) classification systems. Design  This was a case-control study. Setting  This study was set at the University Medical Center. Population  A total of 202 FHR tracings of 102 women who delivered an acidemic fetus (umbilical arterial cord gas pH ≤ 7.10 and BE < - 8) and 100 who delivered a nonacidemic fetus (umbilical arterial cord gas pH > 7.10) were assessed. A subanalysis was performed for those fetuses who suffered severe metabolic acidemia (pH ≤ 7.0 and BE < - 12). Methods  Two reviewers blind to clinical and outcome data classified tracings according to the new 3-tier system proposed by the FIGO and the 5-tier system proposed by Parer and Ikeda. Main Outcome Measures  Sensitivity and specificity for detecting neonatal acidemia and interobserver agreement in classifying FHR tracings into categories of both systems were studied. Results  The 3-tier system showed a greater sensitivity and lower specificity to detect neonatal acidemia (43.6% sensitivity, 82.5% specificity) and severe metabolic acidemia (71.4% sensitivity, 74.0% specificity) compared with the 5-tier system (36.3% sensitivity, 88% specificity and 61.9% sensitivity, 80.1% specificity, respectively). Both systems were compared by area under the receiver-operating characteristic curve, with comparable predictive ability for detecting neonatal acidemia (FIGO-area under the curve [AUC]: 0.63 [95% confidence interval [CI]: 0.57-0.68] and Parer-AUC: 0.62 [95% CI: 0.56-0.67]). Interobserver agreement was moderate for both systems, but performance at each specific category showed a better agreement for the 5-tier system identifying a pathological tracing (orange or red, κ: 0.625 vs. pathological category, κ: 0.538). Conclusion  Both systems presented a comparable ability to predict neonatal acidemia, although the 5-tier system showed a better interobserver agreement identifying pathological tracings. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Small Foci of Serous Component as a Predictor of Recurrence and Prognosis for Stage IA Endometrial Carcinomas.

PubMed

Miyamoto, Morikazu; Takano, Masashi; Tsuda, Hitoshi; Soyama, Hiroaki; Aoyama, Tadashi; Ishibashi, Hiroki; Kato, Kento; Iwahashi, Hideki; Matuura, Hiroko; Yoshikawa, Tomoyuki; Suzuki, Ayako; Hirata, Junko; Furuya, Kenichi

2017-01-01

Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1. © 2017 S. Karger AG, Basel.

Optimization of the extent of surgical treatment in patients with stage I in cervical cancer

NASA Astrophysics Data System (ADS)

Chernyshova, A. L.; Kolomiets, L. A.; Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu.

2016-08-01

The study included 26 patients with FIGO stage Ia1-Ib1 cervical cancer who underwent fertility-sparing surgery (transabdominaltrachelectomy). To visualize sentinel lymph nodes, lymphoscintigraphy with injection of 99mTc-labelled nanocolloid was performed the day before surgery. Intraoperative identification of sentinel lymph nodes using hand-held gamma probe was carried out to determine the radioactive counts over the draining lymph node basin. The sentinel lymph node detection in cervical cancer patients contributes to the accurate clinical assessment of the pelvic lymph node status, precise staging of the disease and tailoring of surgical treatment to individual patient.

Primary invasive carcinoma of the vagina after Le Fort partial colpocleisis for stage IV pelvic organ prolapse: a case report.

PubMed

Cho, Moon Kyoung; Kim, Chul Hong; Kim, Yoon Ha

2011-11-01

We present here the case report of a postmenopausal woman who complained of recurrent pus-like vaginal discharge and perianal pain 1 year after Le Fort colpocleisis, which was subsequently identified as a primary invasive carcinoma of the vagina. Biopsy confirmed a squamous cell carcinoma in the vagina, and the disease was classified as stage III according to FIGO staging. The patient received pelvic radiotherapy. This case emphasizes that differential diagnosis of recurrent vaginal discharge that presents remote from obliterative procedure for pelvic organ prolapse should consider not only pyometra, but also other causes.

``In Vivo'' Dosimetry in High Dose Rate Brachytherapy for Cervical Cancer Treatments

NASA Astrophysics Data System (ADS)

González-Azcorra, S. A.; Mota-García, A.; Poitevín-Chacón, M. A.; Santamaría-Torruco, B. J.; Rodríguez-Ponce, M.; Herrera-Martínez, F. P.; Gamboa de Buen, I.; Ruíz-Trejo, C.; Buenfil, A. E.

2008-08-01

In this prospective study, rectal dose was measured "in vivo" using TLD-100 crystals (3×3×1 mm3), and it has been compared to the prescribed dose. Measurements were performed in patients with cervical cancer classified in FIGO stages IB-IIIB and treated with high dose rate brachytherapy (HDR BT) at the Instituto Nacional de Cancerología (INCan).

Endometrial carcinoma in the baby boomer generation. Tumor characteristics and clinical outcome.

PubMed

Elshaikh, Mohamed A; Cattaneo, Richard; Shah, Mira; Patel, Suketu; Mahan, Meredith; Buekers, Thomas; Siddiqui, Farzan

2013-02-01

Baby boomers (BB) entering retirement represent a significant burden on medical resources. The unique lifestyle characteristics engendered by the BB may lead to different endometrial cancer characteristics that bear understanding. We sought to characterize BB with endometrioid carcinoma after hysterectomy and compare the results to those of prior to the baby boomers (PB). After reviewing our prospectively maintained database of 1,450 patients with endometrial cancer, we identified 595 patients who underwent hysterectomy for 1988 International Federation of Gynecologic Oncology (FIGO) stage I-II uterine endometrioid carcinomas, who were born between 1926 and 1964. Their medical records were reviewed in this Institutional review board (IRB)-approved study. Patients with non-endometrioid carcinoma and those who received preoperative therapy were excluded. Patients were defined as BB (born 1946-1964) or PB (born in 1926-1945). The two groups were compared regarding patients' demographics, tumor characteristics and survival. Following a univariate analysis, multivariable modeling was carried out using Cox regression analysis. All patients underwent hysterectomy with a minimum of two years' follow-up. There were 234 patients (39%) in the BB group and 361 patients (61%) in the PB group. Median follow-up for the study cohort was 56 months. BB had higher body mass index (p=0.027), lower tumor grade (p=0.002), earlier FIGO stage (p=0.023), higher number of dissected lymph nodes (p=0.008), less lymphvascular space involvement (p=<0.034), less utilization of adjuvant therapy (p=<0.001), and younger age at diagnosis (p=0.002). However, there was no significant difference found between the BB and PB in regards to local control, disease-specific survival and overall survival. For the study cohort, FIGO stage and tumor grade were independent predictors of recurrence-free and disease-specific survival. There was a trend towards shorter overall survival for the PB women (p=0.063). Although tumor characteristics were more favorable in the BB group of women, local control and survival end-points were not statistically different compared to those of the PB group. As more BB are diagnosed with endometrial carcinoma, further research is warranted to further elucidate the characteristic differences in endometrial carcinoma, if any, in this generation.

[Correlation between bacterial L-form infection, expression of HIF-1α/MMP-9 and vasculogenic mimicry in epithelial ovarian cancer].

PubMed

Yu, Lan; Wu, Shi-Wu; Zhou, Lei; Song, Wen-Qing

2012-12-25

The aim of the present study is to explore whether vasculogenic mimicry (VM) and bacterial L-form infection exist in human epithelial ovarian cancer (EOC) or not and to elucidate the correlation of L-form infection, expression of hypoxia inducible factor 1α (HIF-1α)/MMP-9 and VM. In 87 specimens of EOC and 20 specimens of ovarian benign epithelial tumor tissues, L-form infection was detected by Gram's staining, expression of HIF-1α/MMP-9 and VM were detected by immunohistochemical and histochemical staining. The results showed that the positive rates of HIF-1α and MMP-9 protein in EOC were 52.9% and 66.7%, while in benign epithelial tumor tissues, the positive rates were 10.0% and 10.0% respectively, and there were significant differences between them (P < 0.05). In EOC and benign epithelial tumor tissues, L-form infections ratios were 24.1% and 0, respectively, and the difference was also significant (P < 0.01). Expression of VM, HIF-1α and MMP-9 in EOC was significantly related to differentiation, abdominal implantation and lymph node metastasis and FIGO stage (P < 0.01). L-form infection had relationship with abdominal implantation, lymph node metastasis and FIGO stage (P < 0.01 or 0.05). The expression of HIF-1α had positive relationship with expression of MMP-9 and VM (r = 0.505, 0.585, respectively, P < 0.01); there was also a positive relationship between MMP-9 expression and VM (r = 0.625, P < 0.01). Overexpression of VM, HIF-1α and MMP-9 were related to poor prognosis: the survival rates were significantly lower in positive patients than those in negative patients (P < 0.05). And the group with L-form infection also had poor prognosis: the survival rates were lower than those in group without infection (P < 0.05). FIGO stage, expression of VM, HIF-1α and MMP-9 were independent prognosis factors of EOC (P < 0.05). The results suggest that L-form infection, the expression of HIF-1α, MMP-9 and VM in EOC are related to differentiation, lymph node metastasis, clinical stage and prognosis. Combined detection of these indexes has an important role in predicting the progression and prognosis of EOC.

Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients.

PubMed

Meng, Xiaodan; Joosse, Simon A; Müller, Volkmar; Trillsch, Fabian; Milde-Langosch, Karin; Mahner, Sven; Geffken, Maria; Pantel, Klaus; Schwarzenbach, Heidi

2015-11-03

Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC. Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines. Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I-II and III-IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III-IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III-IV (P=0.02). Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.

Histopathologic features of ovarian borderline tumors are not predictive of clinical outcome.

PubMed

Avril, Stefanie; Hahn, Ellen; Specht, Katja; Hauptmann, Steffen; Höss, Cornelia; Kiechle, Marion; Höfler, Heinz; Schmalfeldt, Barbara

2012-12-01

Ovarian borderline tumors (BOTs) generally have an excellent prognosis, although recurrences and malignant transformation can occur. Our aim was to compare clinicopathologic features of BOT with clinical outcome. In seventy consecutive BOTs clinicopathologic parameters, tumor cell proliferation (Ki67) and in selected cases KRAS, BRAF and p53 mutational status were analyzed with recurrence-free and overall survival as the endpoints. Sixty-one (87%) patients presented with FIGO stage I, 3 stage II, and 6 stage III. Thirty-four patients had serous and 36 mucinous BOT (30 intestinal and 6 endocervical subtypes). Non-invasive peritoneal implants occurred in 9 patients, and no invasive implants were observed. Recurrence-free and overall survival rates were 91% and 99%, respectively, at a mean follow-up of 63 months. Disease recurrence occurred in 6 cases (all FIGO stage I) including 3 serous, 1 mucinous-intestinal, and 2 mucinous-endocervical subtypes. Mean time to recurrence was 27 months (range 8-68). The recurrence rate following fertility-conserving surgery was 31% (5/16) compared to 2% (1/54) after bilateral salpingo-oophorectomy. Neither peritoneal implants (9/70), micropapillary pattern (2/34), microinvasion (4/70), nor increased tumor cell proliferation was associated with a higher recurrence rate. The frequency of KRAS or BRAF mutations was 50% (3/6 recurrences and 3/6 controls; 4 KRAS, 2 BRAF mutations). No p53 mutations (0/12) were detected in primary or recurrent BOTs. Histopathologic parameters were not predictive of BOT recurrence including previously suggested risk factors such as micropapillary pattern and microinvasion. However, fertility-conserving surgery and incomplete surgical staging were associated with a higher risk for recurrence. Copyright © 2012 Elsevier B.V. All rights reserved.

Definitive radiation therapy for squamous cell carcinoma of the vagina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, Steven J.; Jhingran, Anuja; Levenback, Charles

2005-05-01

Purpose: To evaluate outcome and describe clinical treatment guidelines for patients with primary squamous cell carcinoma of the vagina treated with definitive radiation therapy. Methods and Materials: Between 1970 and 2000, a total of 193 patients were treated with definitive radiation therapy for squamous cell carcinoma of the vagina at The University of Texas M. D. Anderson Cancer Center. The patients' medical records were reviewed to obtain information about patient, tumor, and treatment characteristics, as well as outcome and patterns of recurrence. Surviving patients were followed for a median of 137 months. Survival rates were calculated using the Kaplan-Meier method,more » with differences assessed using log-rank tests. Results: Disease-specific survival (DSS) and pelvic disease control rates correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and tumor size. At 5 years, DSS rates were 85% for the 50 patients with Stage I, 78% for the 97 patients with Stage II, and 58% for the 46 patients with Stage III-IVA disease (p = 0.0013). Five-year DSS rates were 82% and 60% for patients with tumors {<=}4 cm or >4 cm, respectively (p = 0.0001). At 5 years, pelvic disease control rates were 86% for Stage I, 84% for Stage II, and 71% for Stage III-IVA (p = 0.027). The predominant mode of relapse after definitive radiation therapy was local-regional (68% and 83%, respectively, for patients with stages I-II or III-IVA disease). The incidence of major complications was correlated with FIGO stage; at 5 years, the rates of major complications were 4% for Stage I, 9% for Stage II, and 21% for Stage III-IVA (p < 0.01). Conclusions: Excellent outcomes can be achieved with definitive radiation therapy for invasive squamous cell carcinoma of the vagina. However, to achieve these results, treatment must be individualized according to the site and size of the tumor at presentation and the response to initial external-beam radiation therapy. Brachytherapy plays an important role in the treatment of many vaginal cancers but should be carefully selected and applied to obtain optimal coverage of the target volume.« less

Expression and clinical significance of survivin in ovarian cancer: A meta-analysis.

PubMed

He, Xiaoyan; Yang, Kehu; Wang, Hailin; Chen, Xiaohong; Wu, Huifang; Yao, Liang; Ma, Shouye

2018-01-01

To assess the clinicopathological significance of survivin in ovarian carcinoma through this meta-analysis. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were searched for relevant studies published through September, 2017. Included studies reported the case-control study of surviving expression with ovarian cancer and its clinicopathological characteristics. The quality assessment was performed according to the Newcastle-Ottawa Scale (NOS) for quality assessment of case-control studies. Statistical analysis was performed with the software Stata 12.0. Twelve eligible studies with a total of 1097 patients were included in this meta-analysis. Survivin overexpression was closely related to FIGO stage (I-II vs. III-IV) of ovarian carcinoma (odds ratio [OR] = 0.26,95% confidence interval [CI]:0.16,0.42),P<0.00001),tumor grade (G1-G2 vs. G3) (OR = 0.29,95%CI(0.17, 0.51),P <0.0001), but was not significantly associated with lymphatic metastasis (OR = 1.53, 95%CI(0.77, 3.03, P = 0.23),ascites (OR = 0.89,95%CI(0.39,2.05),P = 0.79). Our meta-analysis shows that survivin is strongly associated with FIGO stage and tumor grade of ovarian carcinoma. Maybe survivin is a novel clinicopathological marker of ovarian carcinoma.

Survival of selected patients with ovarian cancer treated with fertility-sparing surgery.

PubMed

Hedbäck, Nora Elisabeth; Karlsen, Mona Aarenstrup; Høgdall, Claus Kim; Rosendahl, Mikkel

2018-04-11

How many patients in Denmark were treated with fertility-sparing surgery (FSS) for epithelial ovarian cancer (EOC) and what was their prognosis compared with patients treated with radical surgery (RS)? This study was a retrospective Danish nationwide study, evaluating the effect of FSS compared with RS in patients with EOC, age ≤45 years and International Federation of Gynecology and Obstetrics (FIGO) stage ≤IC3 from 2005 to 2016. A total of 106 patients were included. Of these, 13 were treated with FSS and 93 were treated with RS. Median age was 27 versus 42 years (P < 0.0001). Overall survival did not differ significantly between the two groups. Overall survival rate in the FSS group was 100%, while the overall survival in the RS group was 87%. Disease-specific survival was 100% in the FSS group and 91% in the RS group. This study shows that patients treated with FSS for FIGO stage I EOC do not have an impaired survival compared with patients treated with RS. Nevertheless, the conclusion must be interpreted with caution due to the limited number of patients and the retrospective nature of the study. Larger studies are needed before conclusions can be drawn. Copyright © 2018. Published by Elsevier Ltd.

Prognostic Significance of Pre-treatment Serum C-Reactive Protein Level in Patients with Adenocarcinoma of the Uterine Cervix.

PubMed

Bodner-Adler, Barbara; Kimberger, Oliver; Schneidinger, Cora; Kölbl, Heinz; Bodner, Klaus

2016-09-01

To evaluate pre-treatment serum C-reactive protein (CRP) level as a prognostic parameter in patients with adenocarcinoma of the uterine cervix. Pre-treatment CRP levels were analyzed to determine potential associations with clinicopathological parameters and to assess prognostic value in 46 patients with sole adenocarcinoma of the uterine cervix. The mean (±SD) pre-treatment serum CRP level was 5.82 (7.21) mg/l. Serum CRP concentration significantly correlated positively with age at diagnosis (p=0.001), lymphovascular space invasion (p=0.0026), recurrent disease (p=0.0001) and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.0002). In multivariate Cox regression models with age, FIGO stage, histological grade and lymph node status, elevated CRP and cancer antigen 125 levels were associated with shortened survival (p<0.05). Overall 5-year survival rate of patients with pre-treatment serum CRP level <5.0 mg/l was 100% compared to 46.9% for patients with pre-treatment CRP level ≥5.0 mg/l. Serum CRP level can be seen as an additional independent prognostic parameter in patients with the rare histological subtype adenocarcinoma of the uterine cervix. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Radiation management of carcinoma of the cervical stump. [Complications following external and internal radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prempree, T.; Patanaphan, V.; Scott, R.M.

1979-04-01

In spite of a low incidence of carcinoma of the cervical stump at the present time, the management of this interesting disease deserves special attention because of the success which can be obtained with proper treatment. Of 107 cases treated, only 100 cases were true cases of carcinoma of the stump and were eligible for this study. 7 cases were excluded from the study because they were probably coincidental carcinomas and were treated soon after subtotal hysterectomy. The lesions were staged according to the FIGO system. 93 cases were invasive squamous cell carcinoma, 6 cases adenocarcinoma and 1 case transitionalmore » cell carcinoma. Of 100 cases with a minimum 5 year follow-up, the absolute 5-year cure rate for various clinical stages is as follows: State I 83.3% (20/24); Stage IIA 75.0% (9/12); Stage IIB 62.5% (20/32); Stage IIIA 50% (1/2); Stage IIIB 48% (12/25); Stage IV 20% (1/5). The overall absolute 5-year cure rate for all stages combined is 63%. A better result in Stage IIIB as compared to several previous reports is thought to be due to extensive and aggressive interstitial radium therapy properly combined with external supervoltage irradiation. Techniques of treatment stage by stage including computerized dosimetry are discussed along with complications and failures.« less

[Current status and recommendations for intrapartum monitoring of fetal heart rate].

PubMed

Měchurová, A; Velebil, P; Hruban, L; Janků, P

2016-04-01

Monitoring of fetal heart rate is one of the basic components of obstetrical care, in which the cardiotocography remains the gold standard and screening method in early diagnosis of fetal hypoxia, even after introduction of other selective methods of intrauterine monitoring of fetal well-being. The review article is divided into several parts: pathophysiology of fetal oxygenation, fetal heart rate and changes of fetal hemodynamics, and rules for fetal heart rate auscultation. The main principles of cardiotocographic monitoring and evaluation of ante- and intrapartrum recordings according to the FIGO criteria from 1986 and evaluation of intrapartum recordings according to the 2015 FIGO recommendations are mentioned. At the end a comparative table of 1986 FIGO and 2015 FIGO criteria is presented. Review.

Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique.

PubMed

Monstad, S E; Storstein, A; Dørum, A; Knudsen, A; Lønning, P E; Salvesen, H B; Aarseth, J H; Vedeler, C A

2006-04-01

Onconeural antibodies are found in patients with cancer and are associated with paraneoplastic neurological syndromes (PNS). The objective of the present study was to assess the frequency of Yo antibodies in ovarian and breast cancer using a sensitive immunoprecipitation technique, and to look for any association of Yo antibodies with neurological symptoms and prognostic factors. A multiwell adapted fluid-phase immunoassay using radiolabelled recombinant cerebellar degeneration related protein (cdr2), produced by coupled in vitro transcription/translation was used for the detection of Yo antibodies. This technique combines high specificity and sensitivity with high sample analysing capacity for the antibody in question. Sera or EDTA-blood from 810 ovarian (n = 557) and breast cancer (n = 253) patients were analysed for Yo antibodies by immunoprecipitation, as well as immunofluorescence and immune blots. Two hundred healthy blood donors and sera from 17 patients with paraneoplastic cerebellar degeneration and Yo antibodies served as controls. Immunoprecipitation was more sensitive in detecting Yo antibodies than immunofluorescence and immune blots. The prevalence of Yo antibodies was 13/557 (2.3%) in ovarian cancer and 4/253 (1.6%) in breast cancer using immunoprecipitation. Yo antibodies were not correlated with specific histological subgroups. The Yo index of ovarian cancer patients in FIGO stage IV was higher compared to FIGO stage I-III. The prevalence of Yo antibodies was 3 times higher in patients with stage III breast cancer than in stage I and II. Only 2/17 (11.8%) patients with Yo antibodies detected during the screen of 810 cancer patients had PNS. The results show that the prevalence of Yo antibodies is low in ovarian and breast cancer. Yo antibodies may be associated with advanced cancer, but less often with PNS.

Trends in the Utilization of Adjuvant Vaginal Cuff Brachytherapy and/or External Beam Radiation Treatment in Stage I and II Endometrial Cancer: A Surveillance, Epidemiology, and End-Results Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Mehul K.; Cote, Michele L.; Ali-Fehmi, Rouba

2012-05-01

Purpose: The optimal adjuvant radiation treatment for endometrial carcinoma (EC) remains controversial. Adjuvant vaginal cuff brachytherapy (VB) has emerged as an increasingly common treatment modality. However, the time trends for using VB, external beam radiation therapy (EBRT), or combined therapy (VB+EBRT) have not been well characterized. We therefore examined the utilization trends of VB, EBRT, and VB+EBRT for adjuvant RT in International Federation of Gynecologic Oncology (FIGO) stage I and II EC over time. Methods and Materials: We evaluated treatment patterns for 48,122 patients with EC diagnosed between January 1995 and December 2005, using the National Cancer Institute's Surveillance, Epidemiology,more » and End Results (SEER) public use database. Chi-squared tests were used to assess differences by radiation type (VB, EBRT, and VB+EBRT) and various demographic and clinical variables. Results: Analyses were limited to 9,815 patients (20.4%) with EC who met the inclusion criteria. Among women who received adjuvant RT, the proportion receiving VB increased yearly (12.9% in 1995 compared to 32.8% in 2005 (p < 0.0001). The increasing use of VB was proportional to the decreasing use of EBRT (56.1% in 1995 to 45.8% in 2005; p < 0.0001) and VB+EBRT (31.0% in 1995 to 21.4% in 2005; p < 0.001). Conclusions: This population-based report demonstrates an increasing trend in the use of VB in the adjuvant setting after hysterectomy for treatment of women with FIGO stage I-II EC. VB alone appears to be replacing pelvic EBRT and VB+EBRT therapy in the management of stage I-II EC.« less

Correlation of PD-1/PD-L1 polymorphisms and expressions with clinicopathologic features and prognosis of ovarian cancer.

PubMed

Tan, Dan; Sheng, Li; Yi, Qing-Hua

2018-02-06

To explore the correlation of PD-1/PD-L1 polymorphisms and their expressions with clinicopathologic features and prognosis of ovarian cancer. A total of 164 patients with ovarian cancer were enrolled as case group and 170 healthy women as control group. We conducted quantitative reverse transcription-PCR (qRT-PCR) to determine PD-1/PD-L1 expressions in peripheral blood mononuclear cells (PBMCs). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification were used to detect PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G. PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk for ovarian cancer. PD-1 rs2227982 C>T was associated with FIGO stage and differentiation grade, while PD-L1 rs4143815 C>G was correlated with histological type and differentiation grade. Besides, PD-1/PD-L1 expressions were positively correlated in PBMCs of patients with ovarian cancer to be associated with differentiation grade. Compared with wild homozygous patients, PD-1/PD-L1 expressions were significantly decreased in PBMCs of ovarian cancer patients carried with the mutant genotypes of rs2227982 C>T and rs4143815 C>G. The PFS and OS in ovarian cancer patients with wild homozygous genotype of rs2227982 C>T and rs4143815 C>G were significantly higher than those with mutant genotypes, which were significantly lower in patients with low expressions of PD-1/PD-L1 than those with high expressions. Univariate COX regression analysis identified FIGO staging, differentiation grade, rs2227982 C>T, rs4143815 C>G and expressions of PD-1/PD-L1 as the prognostic factors, and multivariate COX regression analysis demonstrated that high FIGO stage and low expressions of PD-1/PD-L1 were independent risk factors for the prognosis of ovarian cancer. PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk of ovarian cancer, leading to a poor prognosis, associated with low expressions of PD-1 and PD-L1. While high PD-1 and PD-L1 expressions are indicators of a favorable prognosis in ovarian cancer.

Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway.

PubMed

Wang, Yu; Ma, Jun; Shen, Haoran; Wang, Chengjie; Sun, Yueping; Howell, Stephen B; Lin, Xinjian

2014-11-01

Reactive oxygen species (ROS) can drive the de‑differentiation of tumor cells leading to the process of epithelial-to-mesenchymal transition (EMT) to enhance invasion and metastasis. The invasive and metastatic phenotype of malignant cells is often linked to loss of E-cadherin expression, a hallmark of EMT. Recent studies have demonstrated that hypoxic exposure causes HIF-1-dependent repression of E-cadherin. However, the mechanism by which ROS and/or HIF suppresses E-cadherin expression remains less clear. In the present study, we found that ROS accumulation in ovarian carcinoma cells upregulated HIF-1α expression and subsequent transcriptional induction of lysyl oxidase (LOX) which repressed E-cadherin. Loss of E-cadherin facilitated ovarian cancer (OC) cell migration in vitro and promoted tumor growth in vivo. E-cadherin immunoreactivity correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation and metastasis. Negative E-cadherin expression along with FIGO stage, tumor differentiation and metastasis significantly predicted for a lower 5-year survival rate. These findings suggest that ROS play an important role in the initiation of metastatic growth of OC cells and support a molecular pathway from ROS to aggressive transformation which involves upregulation of HIF-1α and its downstream target LOX to suppress E-cadherin expression leading to an increase in cell motility and invasiveness.

Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis.

PubMed

Qu, Danni; Qu, Hongyan; Fu, Ming; Zhao, Xuelian; Liu, Rong; Sui, Lihua; Zhan, Qimin

2008-08-01

Nlp (Ninein-like protein), a novel centrosome protein involved in microtubule nucleation, has been studied extensively in our laboratory, and its overexpression has been found in some human tumors. To understand the role of Nlp in human ovarian cancer development, we studied the correlation of Nlp expression with clinicopathological parameters and survival in epithelial ovarian cancer, and the impact of Nlp overexpression on ovarian cancer cells. Nlp expression in normal, borderline, benign and malignant epithelial ovarian tissues was examined by immunohistochemistry. The correlation between Nlp expression and tumor grade, FIGO stage and histological type was also evaluated. Survival was calculated using Kaplan-Meier estimates. Cell proliferation and apoptosis were assayed after stable transfection of pEGFP-C3-Nlp or empty vector in human ovarian cancer cell line SKOV3. Nlp was positive in 1 of 10 (10%) normal ovarian tissues, 5 of 34 (14.7%) benign tumors, 9 of 26 (34.6%) borderline tumors and 73 of 131 (56.0%) ovarian tumors. Nlp immunoreactivity intensity significantly correlated with tumor grade, but not with FIGO stage or histological type. Kaplan-Meier curves showed that Nlp overexpression was marginally associated with decreased overall survival. Overexpression of Nlp enhanced proliferation and inhibited apoptosis induced by paclitaxel in the SKOV3 cell line. Overexpression of Nlp in ovarian tumors raises the possibility that Nlp may play a role in ovarian carcinogenesis.

The effect of guideline variations on the implementation of active management of the third stage of labor.

PubMed

Miranda, Jezid E; Rojas-Suarez, Jose; Paternina, Angel; Mendoza, Ray; Bello, Camilo; Tolosa, Jorge E

2013-06-01

To determine whether healthcare providers performed active management of the third stage of labor (AMTSL) as defined by FIGO/ICM and WHO, and as described by the Cochrane Collaboration. In a prospective observational study, a questionnaire regarding knowledge of AMTSL was administered to healthcare providers in the largest maternity teaching center in Colombia. It was subsequently observed whether and how the healthcare providers performed AMTSL in practice. The percentage of correct use of AMTSL was calculated. Healthcare providers indicated they knew what AMTSL was but disagreed on the timing of prophylactic oxytocin use. In total, 241 deliveries were observed. Oxytocin at varying doses and routes was used in 239 (99.2%) deliveries. In all deliveries, the umbilical cord was clamped early. In 49 (20.3%) deliveries, controlled cord traction was performed. Uterine massage was carried out in 213 (88.4%) deliveries. According to the FIGO/ICM and WHO definitions, and the Cochrane Collaboration description, correct use of AMTSL occurred in 0.8%, 0.0%, and 8.3%, of cases, respectively. Correct use of AMTSL is low at the largest maternity teaching center in Colombia. There is an urgent need for a single definition of AMTSL, which could be used globally for research, training, and scaling-up the performance of AMTSL. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Neoadjuvant chemotherapy followed by surgery has no therapeutic advantages over concurrent chemoradiotherapy in International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer.

PubMed

Lee, Jeongshim; Kim, Tae Hyung; Kim, Gwi Eon; Keum, Ki Chang; Kim, Yong Bae

2016-09-01

We aimed to assess the efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S), and compared the clinical outcome with that of concurrent chemoradiotherapy (CCRT) in patients with International Federation of Gynecology and Obstetrics (FIGO) IB-IIB cervical cancer. We reviewed 85 patients with FIGO IB-IIB cervical cancer who received NACT+S between 1989 and 2012, and compared them to 358 control patients who received CCRT. The clinical application of NACT was classified based on the following possible therapeutic benefits: increasing resectability after NACT by reducing tumor size or negative conversion of node metastasis; downstaging adenocarcinoma regarded as relatively radioresistant; and preservation of fertility through limited surgery after NACT. Of 85 patients in the NACT+S group, the pathologic downstaging and complete response rates were 68.2% and 22.6%, respectively. Only two young patients underwent limited surgery for preservation of fertility. Patients of the NACT+S group were younger, less likely to have node metastasis, and demonstrated a higher proportion of FIGO IB cases than those of the CCRT group (p≤0.001). The 5-year locoregional control, progression-free survival, and overall survival rates in the NACT+S group were 89.7%, 75.6%, and 92.1%, respectively, which were not significantly different from the rates of 92.5%, 74%, and 84.9% observed in the CCRT group, respectively (p>0.05). NACT+S has no therapeutic advantages over CCRT, the standard treatment. Therefore, NACT+S should be considered only in selected patients through multidisciplinary discussion or clinical trial setting.

Radiation therapy of primary vaginal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nori, D.; Hilaris, B.S.; Stanimir, G.

1983-10-01

Primary carcinoma of the vagina is rare, constituting only 1 to 2% of all neoplasms arising in the female genital tract. From 1950-1974, 36 patients with carcinoma of the vagina were treated with radiation at Memorial Sloan-Kettering Cancer Center (MSKCC); 35 (96%) had epidermoid carcinoma and one patient (4%) had adenocarcinoma. These patients were staged according to FIGO. Fourteen patients (39%) were Stage I; six patients (17%) were Stage II; three patients (8%) were Stage III; and 13 patients (36%) were Stage IV. Nine patients (25%) were treated with external radiation and interstitial implant; seven patients (20%) were treated withmore » interstitial implant alone; nine patients (25%) were treated with external radiation alone and 11 patients (30%) with external radiation and intracavitary radiation. The five year NED survival was 71% in Stage I, 66% in Stage II, 33% in Stage III and 0% in Stage IV. This paper discusses radiotherapy management of primary carcinoma of the vagina.« less

[Evaluation of mortality after the analysis of the screening history in women diagnosed with infiltrating cervical cancer].

PubMed

Castillo, Marta; Astudillo, Aurora; Clavero, Omar; Velasco, Julio; Ibáñez, Raquel; de Sanjosé, Silvia

2018-03-01

To assess the impact of screening history on the incidence of cervical cancer from 2000 to 2010 in Asturias. Retrospective study. All public hospitals in Asturias. From 374 women diagnosed with cervical cancer were retrieved. Clinical information, FIGO stage and all previous cytological data were extracted from clinical and histopathological records. Proportional differences were assessed using chi-square tests. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals. Women between 25 and 70years had no records of a previous cytology within 5.5years of cancer diagnosis in 65.6%. This proportion was related with older age, presence of symptoms and an advance tumor stage at diagnosis. Women over 70years old had no records of a previous cytology in 83.3%. An organized cervical cancer screening program and optimal quality of the system, monitored through audits, could help to reduce cervical cancer incidence and mortality in Asturias. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation.

PubMed

Buser, K; Bacchi, M; Goldhirsch, A; Greiner, R; Diener, P; Sessa, C; Jungi, W F; Forni, M; Leyvraz, S; Engeler, V

1996-01-01

The primary aim was to induce a high number of pCR in early (FIGO IC, IIB + C) - and advanced (FIGO III-IV) - stage ovarian cancer with a surgery plus 4 cycles of cisplatin and melphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm i.v. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accelerator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinical CR or pathological PR with microscopical residual disease. 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c = clinical, p = pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TTF) and survival. Only 51/118 (43%) patients in remission received WAR. Early-stage patients <= 55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p = 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p = 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (33%) or incompleteness (33%) of irradiation in the majority of patients. PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are needed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pötter, Richard; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna; Federico, Mario

Purpose: To define, in the setting of cervical cancer, to what extent information from additional pretreatment magnetic resonance imaging (MRI) without the brachytherapy applicator improves conformity of CT-based high-risk clinical target volume (CTV{sub HR}) contours, compared with the MRI for various tumor stages (International Federation of Gynecology and Obstetrics [FIGO] stages I-IVA). Methods and Materials: The CTV{sub HR} was contoured in 39 patients with cervical cancer (FIGO stages I-IVA) (1) on CT images based on clinical information (CTV{sub HR}-CT{sub Clinical}) alone; and (2) using an additional MRI before brachytherapy, without the applicator (CTV{sub HR}-CT{sub pre-BT} {sub MRI}). The CT contours were compared withmore » reference contours on MRI with the applicator in place (CTV{sub HR}-MRI{sub ref}). Width, height, thickness, volumes, and topography were analyzed. Results: The CT-MRI{sub ref} differences hardly varied in stage I tumors (n=8). In limited-volume stage IIB and IIIB tumors (n=19), CTV{sub HR}-CT{sub pre-BT} {sub MRI}–MRI{sub ref} volume differences (2.6 cm{sup 3} [IIB], 7.3 cm{sup 3} [IIIB]) were superior to CTV{sub HR}-CT{sub Clinical}–MRI{sub ref} (11.8 cm{sup 3} [IIB], 22.9 cm{sup 3} [IIIB]), owing to significant improvement of height and width (P<.05). In advanced disease (n=12), improved agreement with MR volume, width, and height was achieved for CTV{sub HR}-CT{sub pre-BT} {sub MRI}. In 5 of 12 cases, MRI{sub ref} contours were partly missed on CT. Conclusions: Pre-BT MRI helps to define CTV{sub HR} before BT implantation appropriately, if only CT images with the applicator in place are available for BT planning. Significant improvement is achievable in limited-volume stage IIB and IIIB tumors. In more advanced disease (extensive IIB to IVA), improvement of conformity is possible but may be associated with geographic misses. Limited impact on precision of CTV{sub HR}-CT is expected in stage IB tumors.« less

Para-aortic lymphadenectomy in advanced stage cervical cancer, a protocol for comparing safety, feasibility and diagnostic accuracy of surgical staging versus PET-CT; PALDISC trial.

PubMed

Tax, Casper; Abbink, Karin; Rovers, Maroeska M; Bekkers, Ruud L M; Zusterzeel, Petra L M

2018-01-01

Currently, a PET-CT is used to assess the need for extended field radiotherapy of para-aortic lymph nodes (PALN) in International Federation of Gynaecology and Obstetrics (FIGO) stage IB2, IIA2-IVA (locally advanced stage) cervical cancer. A small study established a sensitivity and specificity estimate for PALN metastases of 50% (95% CI; 7-93%) and 83% (95% CI; 52-98%), respectively. Surgical staging of PALN may lead to a higher diagnostic accuracy. However, surgical staging of para-aortic lymph nodes in locally advanced stage cervical cancer is not common practice. Therefore, a phase 2 randomised controlled trial is needed to assess its safety and feasibility. In addition to standard imaging (MRI or CT scan) with PET-CT, 30 adult women with FIGO stage IB2, IIA2-IVA cervical cancer will be randomised to receive either surgical staging or usual PET-CT staging. Administering extended field radiotherapy will be based on lymphadenectomy results for the intervention group and on the PET-CT results for the control group. Follow-up visits at 0, 3, 6, 9 and 12 months will assess health-related quality of life and progression-free survival.Primary safety and feasibility outcomes of surgical staging will be assessed by calculating means with 95% confidence intervals for duration of surgery, number of complications, blood loss, nodal yield after para-aortic lymphadenectomy and treatment delay due to surgical staging. Secondary patient-centred outcomes on quality of life and first year survival will be documented and compared between the two groups. Estimates of sensitivity, specificity and negative and positive predictive values of MRI, PET-CT and surgical staging will be presented with 95% CI.. All analysis will be performed according to the intention to treat principle. This study will assess safety and feasibility, expressed as the number and severity of complications, effect on quality of life and the treatment delay due to surgically staging para-aortic lymph nodes in locally advanced cervical cancer. It will provide insight in the diagnostic accuracy of the PET-CT and detection rate of missed (micro)metastases due to surgical staging. This information will be used to assess the necessity for a phase 3 study on the diagnostic accuracy of the PET-CT and surgical staging. If a phase 3 study is deemed necessary, current data can be used for sample size calculation of such a phase 3 study. Nederlands Trial Register/Dutch Trial Registry (www.trialregister.nl), NTR4922. Registered on 24 November 2014.

Out of the shadows and 6000 reasons to celebrate: An update from FIGO's fistula surgery training initiative.

PubMed

Slinger, Gillian; Trautvetter, Lilli; Browning, Andrew; Rane, Ajay

2018-06-01

Obstetric fistula is a devastating childbirth injury caused by unrelieved obstructed labor. Obstetric fistula leads to chronic incontinence and, in most cases, significant physical and emotional suffering. The condition continues to blight the lives of 1-2 million women in low-resource settings, with 50 000-100 000 new cases each year adding to the backlog. A trained, skilled fistula surgeon is essential to repair an obstetric fistula; however, owing to a global shortage of these surgeons, few women are able to receive life-restoring treatment. In 2011, to address the treatment gap, FIGO and partners released the Global Competency-Based Fistula Surgery Training Manual, the first standardized curriculum to train fistula surgeons. To increase the number of fistula surgeons, the FIGO Fistula Surgery Training Initiative was launched in 2012, and FIGO Fellows started to enter the program to train as fistula surgeons. Following a funding boost in 2014, the initiative has grown considerably. With 52 fellows involved and a new Expert Advisory Group in place, the program is achieving major milestones, with a record-breaking number of fistula repairs performed by FIGO Fellows in 2017, bringing the total number of repairs since the start of the project to more than 6000. © 2018 International Federation of Gynecology and Obstetrics.

Prognostic significance of number of nodes removed in patients with node-negative early cervical cancer.

PubMed

Mao, Siyue; Dong, Jun; Li, Sheng; Wang, Yiqi; Wu, Peihong

2016-10-01

The aim of this study was to investigate whether the number of removed lymph nodes was associated with survival of patients with node-negative early cervical cancer and to analyze the prognostic significance of clinical and pathologic features in these patients. Patients with FIGO stage IA-IIB cervical cancer who underwent radical hysterectomy with lymphadenectomy without receiving preoperative therapy were reviewed retrospectively. Patients were all proved to have lymph-node-negative disease and classified into five groups based on the number of nodes removed. The Kaplan-Meier method and Cox's proportional hazards regression model were used in prognostic analysis. The final dataset included 359 patients: 45 (12.5%) patients had ≤10 nodes removed, 93 (25.9%) had 11-15, 98 (27.3%) had 16-20, 64 (17.8%) had 21-25, and 59 (16.4%) had >25 nodes removed. There was no association between the number of nodes removed and survival of patients with node-negative early cervical cancer (χ 2  = 6.19, P = 0.185). Similarly, subgroup analyses for FIGO stage IB1-IIB also showed that the number of lymph nodes was not significantly related to survival in each stage. Multivariate analyses showed that histology and depth of invasion were independent prognostic factors for survival in these patients. If a standardized lymphadenectomy is performed, the number of lymph nodes removed is not an independent prognostic factor for patients with node-negative early cervical cancer. Our study suggests that there is inconclusive evidence to support survival benefit of complete lymphadenectomy among these patients. © 2016 Japan Society of Obstetrics and Gynecology.

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.

PubMed

Ren, Tong; Wang, Shu; Sun, Jian; Qu, Ji-Min; Xiang, Yang; Shen, Keng; Lang, Jing He

2017-10-03

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored. We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months. Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients. EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

Telomere length is a prognostic biomarker in elderly advanced ovarian cancer patients: a multicenter GINECO study

PubMed Central

Falandry, Claire; Horard, Béatrice; Bruyas, Amandine; Legouffe, Eric; Cretin, Jacques; Meunier, Jérôme; Alexandre, Jérôme; Delecroix, Valérie; Fabbro, Michel; Certain, Marie-Noëlle; Maraval-Gaget, Raymonde; Pujade-Lauraine, Eric; Gilson, Eric; Freyer, Gilles

2015-01-01

Purpose Age induces a progressive decline in functional reserve and impacts cancer treatments. Telomere attrition leads to tissue senescence. We tested the hypothesis that telomere length (TL) could predict patient vulnerability and outcome with cancer treatment. Patients and methods An ancillary study in the Elderly Women GINECO Trial 3 was performed to evaluate the impact of geriatric covariates on survival in elderly advanced ovarian cancer patients receiving six cycles of carboplatin. TL was estimated from peripheral blood at inclusion using standard procedures. Results TL (in base pairs) was estimated for 109/111 patients (median 6.1 kb; range [4.5-8.3 kb]). With a cut-off of 5.77 kb, TL discriminated two patient groups, long telomere (LT) and short telomeres (ST), with significantly different treatment completion rates of 0.80 (95%CI [0.71-0.89]) and 0.59 (95%CI [0.41-0.76]), respectively (odds ratio [OR]=2.8, p=0.02). ST patients were at higher risk of serious adverse events (SAE, OR=2.7; p=0.02) and had more unplanned hospital admissions (OR=2.1; p=0.08). After adjustment on FIGO stage, TL shorter than 6 kb was a risk factor of premature death (HR=1.57; p=0.06). Conclusion This exploratory study identifies TL as predictive factor of decreased treatment completion, SAE risk, unplanned hospital admissions and OS after adjustment on FIGO stage. PMID:26638179

The role of EMMPRIN expression in ovarian epithelial carcinomas.

PubMed

Zhao, Yang; Chen, Shuo; Gou, Wen-feng; Niu, Zhe-feng; Zhao, Shuang; Xiao, Li-jun; Takano, Yasuo; Zheng, Hua-chuan

2013-09-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas. EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemistry. EMMPRIN siRNA treatment resulted in a lower growth, G 1 arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (P<0.05), and positively correlated with dedifferentiation and FIGO staging (P<0.05). Immunohistochemically, EMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (P<0.05). Upregulated expression of EMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion.

The role of EMMPRIN expression in ovarian epithelial carcinomas

PubMed Central

Zhao, Yang; Chen, Shuo; Gou, Wen-feng; Niu, Zhe-feng; Zhao, Shuang; Xiao, Li-jun; Takano, Yasuo; Zheng, Hua-chuan

2013-01-01

Purpose: Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas. Methods: EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemisty. Results: EMMPRIN siRNA treatment resulted in a lower growth, G1 arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (P < 0.05), and positively correlated with dedifferentiation and FIGO staging (P < 0.05). Immuhistochemically, EMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (P < 0.05). Conclusions: Upregulated expression of EMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion. PMID:23966157

Agreement of three interpretation systems of intrapartum foetal heart rate monitoring by different levels of physicians.

PubMed

Pruksanusak, Ninlapa; Thongphanang, Putthaporn; Chainarong, Natthicha; Suntharasaj, Thitima; Kor-Anantakul, Ounjai; Suwanrath, Chitkasaem; Petpichetchian, Chusana

2017-11-01

A prospective study was conducted in centre in Southern Thailand, to evaluate agreement in EFM interpretation among various physicians in order to find out the most practical system for daily use. We found strong agreement of very normal FHR tracings among the FIGO, NICHD 3-tier and 5-tier systems. The NICHD 3-tier was more compatible with the FIGO system than 5-tier system. Overall inter-observer agreement was moderate for the NICHD 3-tier system while inter-observer agreement of 5-tier system was fair also the intra-observer agreement was higher in the NICHD 3-tier system. So the 3-tier systems are more suitable than the 5-tier system in general obstetric practice. Impact statement What is already known on this subject: The 3-tier and 5-tier systems were widely used in general obstetrics practice. What the results of this study add: The inter- and intra-observer agreement of NICHD 3-tier system was higher than the 5-tier system. What the implications are of these findings for clinical practice and/or further research: The 3-tier systems were more suitable than the 5-tier systems in general obstetrics practice.

Tailoring the field and indication of adjuvant pelvic radiation for patients with FIGO stage Ib lymph nodes-negative cervical carcinoma following radical surgery based on the GOG score--a pilot study.

PubMed

Rushdan, M N; Tay, E H; Khoo-Tan, H S; Lee, K M; Low, J H; Ho, T H; Yam, K L

2004-07-01

The traditional indications for adjuvant pelvic radiotherapy (RT) for International Federation of Obstetrics and Gynecology (FIGO) stage Ib1 lymph nodes-negative cervix carcinoma following radical surgery based on histopathological factors, such as deep stromal invasion and lymphovascular space invasion (LVSI), were often inconsistently applied. The perceived risk of relapse was subjectively determined. This pilot study attempts to determine if the treatment outcome will be affected when the indication for RT is based on the Gynecologic Oncology Group (GOG) Risk Score (RS) and the field of adjuvant RT is tailored to the RS. From 1997 to 1999, 55 patients with FIGO stage Ib1 lymph nodes-negative cervical carcinoma limited to the cervix were prescribed RT following radical surgery, based on their RS, as follows: RS <40, RT is omitted; RS >40 to <120, modified (smaller) field RT; and RS >120, standard field pelvic RT. Their incidence and site of recurrence were compared with a similar cohort of 40 patients who were treated prior to 1997. Prior to 1997, of the 40 patients, 10 patients were given standard field RT. There were 2 (5%) recurrent diseases. The mean duration of follow-up was 61.6 months (range, 1 to 103 months). The RS of 23 of the 30 patients who were not given RT were available. The mean RS was 22 with 5 patients having a score of >40. From 1997 onwards, of the 55 patients, 28 (51%) did not require RT, 13 (23%) were treated with modified (smaller) field RT and 14 (26%) were given standard field RT. There were 2 (3.6%) cases of relapse. The mean duration of follow-up was 36.4 months (range, 5 to 60 months). All patients with a RS of <40 did not suffer any relapse. Their survival outcomes were better when compared to patients who did not have any RT in the GOG Study. The results of this study indicated that postoperative adjuvant RT given to patients with a high GOG RS of >120, significantly improved their 5-year recurrence rate and disease-free survival, as compared with the similar group of patients who were without adjuvant therapy in the GOG study. Patients with a GOG risk-score of <40 may be safely spared from adjuvant pelvic RT. The current treatment protocol did not compromise the outcome in patients, compared with the use of a less precise treatment protocol in the past.

Borderline tumors of the ovary: A clinicopathological study

PubMed Central

Yasmeen, Samia; Hannan, Abdul; Sheikh, Fareeha; Syed, Amir Ali; Siddiqui, Neelam

2017-01-01

Objective: To report experience with borderline ovarian tumors (BOTs) in a developing country like Pakistan with limited resources and weak database of health system. Methods: Patients with BOTs managed at Shaukat Khanum Cancer hospital, Lahore, Pakistan from 2004 to 2014 were included and reviewed retrospectively. Data was recorded on histopathological types, age, CA-125, stage of disease, treatment modalities and outcomes. Results: Eighty-six patients with BOT were included with a median age of 35 years. Forty-two (49%) patients had serous BOTs and 43 (50%) had mucinous BOTs, while one (1%) had mixed type. Using FIGO staging, 80 patients had stage I; two patients had IIA, IIB and stage III each. Median follow-up time was 31.5 months. All patients had primary surgery. Seventy (81%) patients underwent complete surgical resection of tumor. Forty-three (50%) patients had fertility preserving surgery. Seventy-three (85%) patients remained in remission. Recurrent disease was observed in 13 (15%) patients. Median time to recurrence was 22 months. On further analysis, age above forty years, late stage at diagnosis and incomplete surgery were significantly associated with invasive recurrence. Conclusion: Despite a low malignant potential, relapses may occur in patients above forty years of age, incomplete surgery and staging information and advanced stage at presentation. Fertility sparing surgery should be considered in young patients. Complete excision of tumor and prolonged follow-up are advised because recurrence and transformation to invasive carcinoma may occur. PMID:28523039

[Conservative treatment of ectopic pregnancy in a 27 years old patient with stage-Ia ovarian cancer after conservative surgical treatment and chemotherapy].

PubMed

Malinowski, Andrzej; Augustyniak, Tomasz; Bartosiak, Ilona; Maciołek-Bleniewska, Grazyna; Ciesielski, Arkadiusz

2004-01-01

We report a case of conservative treatment of ectopic pregnancy in a 27 years old patient, previously treated for ovarian cancer. Two years before she had surgery because of tumour in the left ovary. Ovarian cancer in stage la according to FIGO was confirmed. Considering the patient s young age, future reproductive plans and the early stage of cancer, the patient qualified for conservative treatment. Left adnexectomy with consequent chemotherapy (6 courses) was performed. Two years later on the ground of clinical symptoms, gynaecologic examination, sonography and changes in HCG serum concentration, ectopic pregnancy was recognised in the right tube. We applied conservative management with intramuscularly administrated Methotrexate. The patient, in good condition, was discharged from hospital on day 12 after injection of Methotrexate.

Is the two-tier ovarian serous carcinoma grading system potentially useful in stratifying uterine serous carcinoma? A large multi-institutional analysis.

PubMed

Ahmed, Quratulain; Hussein, Yaser; Hayek, Kinda; Bandyopadhyay, Sudeshna; Semaan, Assaad; Abdul-Karim, Fadi; Al-Wahab, Zaid; Munkarah, Adnan R; Elshaikh, Mohamed A; Alosh, Baraa; Nucci, Marisa R; Van de Vijver, Koen K; Morris, Robert T; Oliva, Esther; Ali-Fehmi, Rouba

2014-02-01

A subset of uterine serous carcinoma (USC) may have better clinical behavior bringing up the possibility that there may be morphologic features, which would help in their categorization. The aim of this study is to evaluate the potential use of the MD Anderson Cancer Center 2-tier grading system for ovarian carcinoma in USC. Tumors assigned a combined score included in this analysis were 1) low-grade: tumors without marked atypia and 12 mitoses/10 high power field (HPF) and 2) high grade: tumors with severe nuclear atypia and >12 mitoses/10 HPF. Clinicopathologic parameters evaluated included patients' age, tumor size, myometrial invasion (MI), lymphovascular invasion (LVI), lymph node (LN), FIGO stage, and patient outcome. 140 patients with USC were included, 30 low grade uterine serous carcinoma (LGUSC) and 110 high grade uterine serous carcinoma (HGUSC). Of all parameters only 2 (MI and stage IA) reached statistical significance. 67% of LGUSC cases showed myometrial invasion versus 93.6% HGUSC cases (p = 0.003). A higher percentage of LGUSC (63.3%) versus HGUSC (32.7%) were in stage IA (p = 0.01). However, by multivariate analysis including age, LVI, stage and tumor grade only stage was an independent prognostic factor. The presence of atypia and mitosis across a uterine serous carcinoma is notoriously variable in magnitude and extent, potentially making evaluation of these features difficult and subsequent grading subjective. Our findings thus show that actual prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma may not be applicable. Copyright © 2013 Elsevier Inc. All rights reserved.

Signal loss during fetal heart rate monitoring using maternal abdominal surface electrodes between 28 and 42 weeks of pregnancy.

PubMed

Fuchs, Tomasz; Pomorski, Michał; Grobelak, Krzysztof; Tomiałowicz, Marek; Zimmer, Mariusz

2014-01-01

Fetal electrocardiography is one of the methods for monitoring the well-being of the fetus. Signal loss limits the proper interpretation of electrocardiogram traces. The aim of this study was to assess the average signal loss in non-invasive abdominal fetal electrocardiogram (fECG) monitoring using the KOMPOREL fetal monitoring system (ITAM, Zabrze, Poland) in women between 28 and 42 week of pregnancy. The results were compared to FIGO (International Federation of Gynaecology and Obstetric) and DGGG (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e.V.) recommendations concerning fetal heart monitoring. The correlation between fetal ECG signal quality, week of pregnancy and patient BMI was evaluated. 773 pregnant women, hospitalized and diagnosed in the Department of Gynecology and Obstetrics, Wroclaw Medical University, underwent 30 min of abdominal fECG recordings using the KOMPOREL fetal monitoring system. The average signal loss in abdominal fECG monitoring in the study group was 32%. FIGO recommendations describe an acceptable fetal signal loss of 20%. In our study, 46% (357/773) of the recordings were up to FIGO standards, with fetal heart rate success rates above 80%. According to DGGG guidelines, with acceptable fetal signal loss of 15%, only 39% (303/773) of the recordings could be assessed as accurate. No correlation between fECG signal quality, week of pregnancy and patient BMI was proved. The average signal loss in abdominal fECG monitoring in our study group was 32%. Low fECG signal quality may constitute a potentially limiting factor of the described fetal heart monitoring system. No relationship between fECG signal quality, week of pregnancy and patient BMI was proved.

Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study.

PubMed

Diaz De Vivar, Andrea; Roma, Andres A; Park, Kay J; Alvarado-Cabrero, Isabel; Rasty, Golnar; Chanona-Vilchis, Jose G; Mikami, Yoshiki; Hong, Sung R; Arville, Brent; Teramoto, Norihiro; Ali-Fehmi, Rouba; Rutgers, Joanne K L; Tabassum, Farah; Barbuto, Denise; Aguilera-Barrantes, Irene; Shaye-Brown, Alexandra; Daya, Dean; Silva, Elvio G

2013-11-01

The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant.

Constitutive STAT5 Activation Correlates With Better Survival in Cervical Cancer Patients Treated With Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Helen H.W.; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Chou, Cheng-Yang

2012-02-01

Purpose: Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3, and STAT5, have been detected in a wide variety of human primary tumors and have been demonstrated to directly contribute to oncogenesis. However, the expression pattern of these STATs in cervical carcinoma is still unknown, as is whether or not they have prognostic significance. This study investigated the expression patterns of STAT1, STAT3, and STAT5 in cervical cancer and their associations with clinical outcomes in patients treated with radical radiation therapy. Methods and Materials: A total of 165 consecutive patients with International Federation of Gynecologymore » and Obstetrics (FIGO) Stages IB to IVA cervical cancer underwent radical radiation therapy, including external beam and/or high-dose-rate brachytherapy between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and to evaluate the effects of these factors affecting patient survival. Results: Constitutive activations of STAT1, STAT3, and STAT5 were observed in 11%, 22%, and 61% of the participants, respectively. While STAT5 activation was associated with significantly better metastasis-free survival (p < 0.01) and overall survival (p = 0.04), STAT1 and STAT3 activation were not. Multivariate analyses showed that STAT5 activation, bulky tumor ({>=}4 cm), advanced stage (FIGO Stages III and IV), and brachytherapy (yes vs. no) were independent prognostic factors for cause-specific overall survival. None of the STATs was associated with local relapse. STAT5 activation (odds ratio = 0.29, 95% confidence interval = 0.13-0.63) and advanced stage (odds ratio = 2.54; 95% confidence interval = 1.03-6.26) were independent predictors of distant metastasis. Conclusions: This is the first report to provide the overall expression patterns and prognostic significance of specific STATs in cervical carcinoma. Our results indicate that constitutive STAT5 activation correlates with better metastasis-free survival and overall survival in cervical cancer patients who have received radiation therapy.« less

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

PubMed

Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

2014-01-01

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

Both germ line and somatic genetics of the p53 pathway affect ovarian cancer incidence and survival.

PubMed

Bartel, Frank; Jung, Juliane; Böhnke, Anja; Gradhand, Elise; Zeng, Katharina; Thomssen, Christoph; Hauptmann, Steffen

2008-01-01

Although p53 is one of the most studied genes/proteins in ovarian carcinomas, the predictive value of p53 alterations is still ambiguous. We performed analyses of the TP53 mutational status and its protein expression using immunohistochemistry. Moreover, the single nucleotide polymorphism SNP309 in the P2 promoter of the MDM2 gene was investigated. We correlated the results with age of onset and outcome from 107 patients with ovarian carcinoma. In our study, we identified a large group of patients with p53 overexpression despite having a wild-type gene (49% of all patients with wild-type TP53). This was associated with a significantly shortened overall survival time (P = 0.019). Patients with p53 alterations (especially those with overexpression of wild-type TP53) were also more refractory to chemotherapy compared with patients with normal p53 (P = 0.027). The G-allele of SNP309 is associated with an earlier age of onset in patients with estrogen receptor-overexpressing FIGO stage III disease (P = 0.048). In contrast, in patients with FIGO stage III disease, a weakened p53 pathway (either the G-allele of SNP309 or a TP53 mutation) was correlated with increased overall survival compared with patients whose tumors were wild-type for both TP53 and SNP309 (P = 0.0035). Our study provides evidence that both germ line and somatic alterations of the p53 pathway influence the incidence and survival of ovarian carcinoma, and it underscores the importance of assessing the functionality of p53 in order to predict the sensitivity of platinum-based chemotherapies and patient outcome.

Impact of hospital type and treatment on long-term survival among patients with FIGO Stage IIIC epithelial ovarian cancer: follow-up through two recurrences and three treatment lines in search for predictors for survival.

PubMed

Szczesny, W; Vistad, I; Kaern, J; Nakling, J; Tropé, C; Paulsen, T

2016-01-01

The purpose of this study was to investigate the impact of hospital type determined at primary treatment and find possible predictors of survival in a cohort of patients with advanced epithelial ovarian cancer (EOC) who recurred twice and received three lines of treatment during eight-year follow-up. Using the Norwegian Cancer Registry, the authors identified 174 women with FIGO Stage IIIC EOC diagnosed in 2002. First-line treatment consisted of up-front debulking surgery and chemotherapy, received in either a teaching hospital (TH, n = 84) or a non-teaching hospital (NTH, n = 90). After recurrence all patients in Norway are equally consulted at TH. Survival determined for three time intervals (TI): TI-1, from end date of first-line treatment to first recurrence or death, TI-2, from beginning of second-line treatment until second recurrence or death, and TI-3, from beginning of third-line treatment to death or end of follow-up. Extensive surgery carried out in TH followed by at least six cycles of platinol-taxan chemotherapy resulted in longer survival in the TH group during TI-1. Altogether, the majority of those who receive treatment for recurrences were primary better debulked with following platinol-taxane chemotherapy. Survival in TI-2 was influenced by platinol-sensitivity. During TI-3 the majority (96%) had good performance status and their mean age at primary diagnosis at either hospital type was 57 years. Extensive primary surgery at TH, platinol sensitivity, age, and performance status were predictors of survival in this cohort.

Early invasive (FIGO stage IA) carcinoma of the cervix: a clinico-pathologic study of 476 cases.

PubMed

Elliott, P.; Coppleson, M.; Russell, P.; Liouros, P.; Carter, J.; MacLeod, C.; Jones, M.

2000-01-01

The clinical and histologic features of 476 tumors fitting the 1995 FIGO definition of stage IA cervical cancer, treated at a Sydney tertiary referral hospital between 1953 and 1992, are reviewed. Five-year follow-up was complete with a median of 10 years. The diagnosis was increasingly made by histologic examination of colposcopically directed cone biopsy. The majority (88%) of tumors were squamous. The proportion of both younger women (3 mm. Treatment was surgical in 99% and was increasingly more conservative as the study progressed with no apparent increase in treatment failure. From 1973 treatment by cone biopsy rose from 6.5 to 35%, by radical hysterectomy fell from 51 to 21% and by lymphadenectomy from 53 to 26%. Only one of 115 patients treated by cone biopsy died. Positive lymph nodes were detected in 1.7% of 180 patients undergoing lymphadenectomy. There were 16 recurrences (3.4%); six vaginal with no cancer deaths, nine pelvic and one distant, with nine deaths and three new cancers (two deaths). Univariate analysis suggests that older age, glandular tumors and those invading 3 mm were associated with more treatment failures and multivariate analysis showed that both conservative hysterectomy and the omission of lymphadenectomy are associated with higher recurrence rates with >3 mm invasion. The study failed to resolve the dilemma of predicting those tumors with a poor prognosis.

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma

PubMed Central

Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

2014-01-01

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor. PMID:24817962

CD44v3 and VEGF-C expression and its relationship with lymph node metastasis in squamous cell carcinomas of the uterine cervix.

PubMed

Liu, Ye-Qing; Li, Hai-Feng; Han, Jing-Jing; Tang, Qiong-Lan; Sun, Qing; Huang, Zhi-Quan; Li, Hai-Gang

2014-01-01

To investigate the expression of CD44v3 and vascular endothelial growth factor-C (VEGF-C) and their relationship with lymph node metastasis in squamous cell carcinomas (SCC) of the uterine cervix. Expression of CD44v3 and VEGF-C was analyzed in 109 cases of cervical SCC by immunohistochemistry (IHC). The relationship was analyzed between expression and the patient age, histological differentiation, formation of tumor emboli in lymphoid vessels, lymph node metastasis, FIGO staging, and TNM classification. Expression rates for both CD44v3 and VEGF-C were 43.1% in cervical SCC. The cells with positive immunohistochemical staining of CD44v3 were distributed mainly around the keratin pearls in well differentiated carcinomas, but distributed diffusely in the moderately and poorly differentiated lesions. VEGF-C was found stained positively in most of the tumor cells. There were differences in expression between normal epithelium and atypical hyperplasia as well as carcinoma. Both CD44v3 and VEGF-C were found to be associated positively with lymph node metastasis and TNM classification (both p=0.000). Neither CD44v3 nor VEGF-C was found to be associated with patient age, histological differentiation, formation of tumor emboli in lymphoid vessels and FIGO staging. CD44v3 was found to be associated with VEGF-C positively (p=0.000). Abnormal expression of CD44v3 and VEGF-C is associated closely with the lymph node metastasis in cervical SCC, and these agents may cooperate in carcinogenesis and development of metastatic lesions.

Prognostic significance of normal-sized ovary in advanced serous epithelial ovarian cancer.

PubMed

Paik, E Sun; Kim, Ji Hye; Kim, Tae Joong; Lee, Jeong Won; Kim, Byoung Gie; Bae, Duk Soo; Choi, Chel Hun

2018-01-01

We compared survival outcomes of advanced serous type epithelial ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian tumors by propensity score matching analysis. The medical records of EOC patients treated at Samsung Medical Center between 2002 and 2015 were reviewed retrospectively. We investigated EOC patients with high grade serous type histology and International Federation of Gynecology and Obstetrics (FIGO) stage IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant chemotherapy to identify patients with normal-sized ovaries. Propensity score matching was performed to compare patients with normal-sized ovaries to patients with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial cancer antigen (CA)-125 level, and residual disease status after PDS. Of the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged-ovarian tumor were younger (54.0±10.3 vs. 58.4±9.2 years, p=0.005) than those with normal-sized ovary, and there was a statistically significant difference in residual disease status between the 2 groups. In total cohort with a median follow-up period of 43 months (range, 3-164 months), inferior overall survival (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months; p=0.003). After propensity score matching, the group with normal-sized ovary showed inferior OS compared to the group with enlarged-ovarian tumor (median OS, 72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized ovary remained a significant factor. Normal-sized ovary was associated with poor OS compared with the common presentation of enlarged ovaries in EOC, independent of CA-125 level or residual disease. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Polypoid nodular histiocytic hyperplasia associated with endometrioid adenocarcinoma of the endometrium: report of a case

PubMed Central

2014-01-01

A 45 year old woman underwent Laparoscopy-assisted total hysterectomy with staging procedure following a diagnosis of endometrial endometrioid adenocarcinoma on her endometrial biopsy. The hysterectomy specimen showed a FIGO I stage 1a, endometrioid carcinoma. A separate polypoid lesion in the endometrium, distinct from the carcinoma, was also identified. Microscopically the polypoid lesion was “nodular histiocytic hyperplasia”. The H&E, immunohistochemical staining findings and the differential diagnoses are discussed in this report. Although description of similar lesions is available in the literature, the current lesion is unique as it is identified in a hysterectomy specimen in its entirety and its association with an endometrial endometrioid carcinoma. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060511915121922 PMID:24885845

Randomized study of whole-abdomen irradiation versus pelvic irradiation plus cyclophosphamide in treatment of early ovarian cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sell, A.; Bertelsen, K.; Andersen, J.E.

From 1 September 1981 to 1 January 1987, 118 patients with FIGO Stage IB, IC, IIA, IIB, and IIC epithelial ovarian cancer were randomized to abdominal irradiation or pelvic irradiation + cyclophosphamide. There was no difference between the regimens with respect to recurrence-free survival (55%) and 4-year overall survival (63%). At routine second-look laparotomy, 16% of patients without clinical detectable tumor showed recurrence. Twenty-five percent of the patients treated with pelvic irradiation + cyclophosphamide had hemorrhagic cystitis, probably caused by radiation damage and cyclophosphamide cystitis. Eight percent had late gastrointestinal symptoms requiring surgery.

Practical aspects of the two FIGO systems for management of abnormal uterine bleeding in the reproductive years.

PubMed

Munro, Malcolm G

2017-04-01

The FIGO systems defining the nomenclature and symptoms of abnormal uterine bleeding (AUB) in the reproductive years (System 1) and the PALM-COEIN classification of causes of AUB (System 2) are designed to facilitate research, education, and the provision of optimum clinical care for affected women. Development of these systems has been the result of a collaborative effort of experts in bench and translational and clinical research from six continents aided by a spectrum of representatives from relevant medical societies, journals, and regulatory bodies. Integral to this development has been a decision to cease the use of poorly defined and inconsistently used terms such as menorrhagia, metrorrhagia, and dysfunctional uterine bleeding, to name a few, and replace them with a set of terms and definitions that are relatively easily understood and translated into the spectrum of languages used by medical providers and patients globally. The utilization of these systems requires a disciplined approach to obtaining a menstrual history, relatively simple laboratory investigations, and the appropriate use of imaging techniques accessible to most clinicians worldwide. This section describes the two systems, their crucial role in guiding investigation, and an approach to implementation, all designed to facilitate the creation of a menu of therapeutic options, considering the identified factors contributing to the problem of nongestational AUB. Copyright © 2016. Published by Elsevier Ltd.

Underscreened Women Remain Overrepresented in the Pool of Cervical Cancer Cases in Spain: A Need to Rethink the Screening Interventions.

PubMed

Ibáñez, Raquel; Alejo, María; Combalia, Neus; Tarroch, Xavier; Autonell, Josefina; Codina, Laia; Culubret, Montserrat; Bosch, Francesc Xavier; de Sanjosé, Silvia

2015-01-01

Audit of women with invasive cervical cancer (CC) is critical for quality control within screening activities. We analysed the screening history in the 10 years preceding the study entry in women with and without CC during 2000-2011. 323 women with CC from six pathology departments in Catalonia (Spain) and 23,782 women with negative cytology were compared. Age, previous history of cytologies, and histological type and FIGO stage were collected from the pathology registries. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI95%). History of cytology was registered in 26.2% of CC cases and in 78% of the control women (P < 0.0001) and its frequency decreased with increasing age. Compared to women with squamous cell carcinoma, adenocarcinoma cases were significantly more likely to have a cytology within the 3-year interval preceding cancer diagnosis (OR = 2.6 CI 95%: 1.2-5.6) and to have normal cytology results in previous screenings (OR = 2.4 CI 95%: 1.2-4.5). FIGO II-IV cases were more common among older women (older than 60 years). Absence of prior screening history was extremely common among CC cases compared to controls. Organized actions to reduce underscreened women and use of highly sensitive HPV-based tests could be important to reduce CC burden.

Mucinous Cystadenocarcinoma Co-Existing with Mature Cystic Teratoma : A Rare Case Report

PubMed Central

Yeshvanth, Sunil Kumar; Shrinivas, Teerthanath; Agrawal, Tanu; Shetty, Jayaprakash K

2015-01-01

Co-existence of mucinous cystadenocarcinoma with mature cystic teratoma in the same ovary is very rare. We report a case in a 48-year-old female who presented with left abdominal mass. CT scan revealed a heterogeneous enhancing left ovarian mass lesion. Clinical diagnosis of complex ovarian cyst was made, later underwent laparotomy and histologically diagnosed as mucinous cystadenocarcinoma (grade 2) co-existing with benign cystic teratoma, stage Ia (FIGO) of the left ovary. Six months after surgery, the patient is doing well without any recurrence or metastasis. Hence, histopathological examination plays a significant role in accurate diagnosis and management of the patient. So, we should be aware of these rare co-existent tumours and meticulous dissection should be done to look for any synchronous tumours or malignant areas; since management and prognosis will vary significantly depending upon the microscopic type and stage. PMID:26393136

Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands.

PubMed

Luttjeboer, Jos; Setiawan, Didik; Cao, Qi; Cahh Daemen, Toos; Postma, Maarten J

2016-12-07

In this study, the potential price for a therapeutic vaccine against Human Papilloma Virus (HPV)-16 & 18 (pre)-malignant cervical lesions is examined. A decision tree model was built in the context of the new Dutch cervical cancer-screening program and includes a primary test for the presence of HPV. Based on data of cervical cancer screening and HPV prevalence in the Netherlands, cohorts were created with HPV-16 or 18 positive women with cervical intraepithelial neoplasia (CIN) 2 or 3 or cervical cancer stage 1A (FIGO 1A). In the base case, the vaccine price was based on equal numbers of effective treatments in the vaccine branch and the current treatments branch of the model, and parity in cost, i.e. total cost in both branches are the same. The vaccine price is calculated by subtracting the cost of the vaccine branch from cost in the standard treatment branch and divided by the total number of women in the cohort, thereby equalizing costs in both strategies. Scenario analyses were performed taking quality adjusted life years (QALYs) into account with €20,000/QALY, €50,000/QALY and €80,000/QALY as corresponding thresholds. Sensitivity analyses were specifically targeted at the characteristics of the type-specific HPV test in the screening practice and vaccine efficacy. A probabilistic sensitivity analysis (PSA) was performed to quantify the level of uncertainty of the results found in the base case. In the base case, break-even vaccine prices of €381, €568 and €1697 were found for CIN 2, CIN 3 and FIGO 1A, respectively. The PSA showed vaccine pricing below €310, €490 and €1660 will be cost saving with a likelihood of 95% for CIN 2, CIN 3 and FIGO 1A, respectively. The vaccine price proved to be very sensitive for inclusion of QALY gains, including the HPV-type specific test into the Dutch screening practice and vaccine efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doll, Corinne M., E-mail: Corinne.Doll@albertahealthservices.ca; Aquino-Parsons, Christina; Pintilie, Melania

2013-03-01

Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens weremore » retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis.« less

Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study.

PubMed

Trillsch, F; Mahner, S; Woelber, L; Vettorazzi, E; Reuss, A; Ewald-Riegler, N; de Gregorio, N; Fotopoulou, C; Schmalfeldt, B; Burges, A; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H G; Hellriegel, M; Wimberger, P; Baumann, K; Keyver-Paik, M D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Kommoss, F; Hauptmann, S; du Bois, A

2014-07-01

Approximately one-third of all borderline ovarian tumours (BOT) are diagnosed in patients with child-bearing potential. Detailed information regarding their specific characteristics and prognostic factors is limited. Clinical parameters of BOT patients treated between 1998 and 2008 in 24 German centres were retrospectively investigated. Central pathology review and prospective follow-up were carried out. Patients <40 versus ≥40 years were analysed separately and then compared regarding clinico-pathological variables and prognosis. A total of 950 BOT patients with a median age of 49.1 (14.1-91.5) years were analysed [280 patients <40 years (29.5%), 670 patients ≥40 years (70.5%)]. Fertility-preserving surgery was carried out in 53.2% (149 of 280) of patients <40 years with preservation of the primarily affected ovary in 32 of these 149 cases (21.5%). Recurrence was significantly more frequent in patients <40 years (19.0% versus 10.1% 5-year recurrence rate, P < 0.001), usually in ovarian tissue, whereas disease-specific overall survival did not differ between the subgroups. In case of recurrent disease, malignant transformation was less frequent in younger than in older patients (12.0% versus 66.7%, P < 0.001), mostly presenting as invasive peritoneal carcinomatosis. Multivariate analysis for patients <40 years identified advanced International Federation of Gynecology and Obstetrics (FIGO) stage and fertility-sparing approach as independent prognostic factors negatively affecting progression-free survival (PFS) while, for patients ≥40 years, higher FIGO stage and incomplete staging was associated with impaired PFS. Despite favourable survival, young BOT patients with child-bearing potential are at higher risk for disease recurrence. However, relapses usually remain BOT in the preserved ovaries as opposed to older patients being at higher risk for malignant transformation in peritoneal or distant localisation. Therefore, fertility-sparing approach can be justified for younger patients after thorough consultation. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The retrospective analysis of patients with uterine sarcomas: A single-center experience.

PubMed

Terek, Mustafa Cosan; Akman, Levent; Hursitoglu, Behiye Seda; Sanli, Ulus Ali; Ozsaran, Zeynep; Tekindal, Mustafa Agah; Dikmen, Yilmaz; Zekioglu, Osman; Ozsaran, Ahmet Aydin

2016-01-01

Uterine sarcomas are rare, malignant, gynecological tumors and show diverse histopathological features. Therefore, there is no consensus on risk factors for poor outcome and optimal treatment. The aim of this retrospective analysis is to report the clinical outcome of patients with uterine sarcoma treated at a single center. The data was obtained regarding the patient's demographic characteristics, pathological results, treatments given, survival, and complications of all uterine sarcoma patients treated in a single center between the years 2000 and 2012. The 80.month overall survival. (OS) was determined with respect to prognostic factors including age, stage of disease, histopathological type, and adjuvant treatment. A total of 57 case records are retrieved for this retrospective analysis. The mean age of the patients is 62.5 ± 11.2 years. International Federation of Gynecology and Obstetrics (FIGO) stage distribution is stage I: 29; stage II: 13; stage III: 9; stage IV: 6. Fifty-seven patients underwent surgery, 33 received postoperative radiotherapy (PORT), and 32 received chemotherapy. Median follow-up period was 25 months (range 2-85 months). The 80-month OS for the entire group of patients was 36.7%. The significant prognostic factors for survival are age under 50 years, stage of disease, and adjuvant chemotherapy. Although limited by small sample size and retrospective nature, age under 50 years, stage of disease, and adjuvant chemotherapy are significant prognostic factors for survival for uterine sarcomas.

Underscreened Women Remain Overrepresented in the Pool of Cervical Cancer Cases in Spain: A Need to Rethink the Screening Interventions

PubMed Central

Alejo, María; Combalia, Neus; Tarroch, Xavier; Autonell, Josefina; Codina, Laia; Culubret, Montserrat; Bosch, Francesc Xavier; de Sanjosé, Silvia

2015-01-01

Objective. Audit of women with invasive cervical cancer (CC) is critical for quality control within screening activities. We analysed the screening history in the 10 years preceding the study entry in women with and without CC during 2000–2011. Methods. 323 women with CC from six pathology departments in Catalonia (Spain) and 23,782 women with negative cytology were compared. Age, previous history of cytologies, and histological type and FIGO stage were collected from the pathology registries. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI95%). Results. History of cytology was registered in 26.2% of CC cases and in 78% of the control women (P < 0.0001) and its frequency decreased with increasing age. Compared to women with squamous cell carcinoma, adenocarcinoma cases were significantly more likely to have a cytology within the 3-year interval preceding cancer diagnosis (OR = 2.6 CI 95%: 1.2–5.6) and to have normal cytology results in previous screenings (OR = 2.4 CI 95%: 1.2–4.5). FIGO II–IV cases were more common among older women (older than 60 years). Conclusions. Absence of prior screening history was extremely common among CC cases compared to controls. Organized actions to reduce underscreened women and use of highly sensitive HPV-based tests could be important to reduce CC burden. PMID:26180804

Residual tumour volumes and grey zones after external beam radiotherapy (with or without chemotherapy) in cervical cancer patients. A low-field MRI study.

PubMed

Schmid, M P; Mansmann, B; Federico, M; Dimopoulous, J C A; Georg, P; Fidarova, E; Dörr, W; Pötter, R

2013-03-01

Grey zones, which are defined as tissue with intermediate signal intensity in the area of primary hyperintense tumour extension, can be seen during radiation with or without chemotherapy on the T2-weighted MRI in patients with cervical cancer. The purpose of this study was to systematically measure the tumour volume at the time of diagnosis and the residual tumour volume at the time of brachytherapy without and with consideration of the grey zones and to estimate tumour regression during external beam radiotherapy (EBRT). T2-weighted MRI datasets of 175 patients with locally advanced cervical cancer (FIGO stage IB-IVA), who underwent combined external beam radiotherapy and brachytherapy with or without concomitant chemotherapy were available for this study. The gross tumour volume at the time of diagnosis (GTV(init)) and at the time of first brachytherapy without (GTV(res)) and with (GTV(res)+ GZ) consideration of grey zones were measured for each patient. A descriptive statistical analysis was performed and tumour regression rates without (R) and with consideration of grey zones (R(GZ)) were calculated. Further, the role of prognostic factors on GTV(init), GTV(res), GTV(res)+ GZ and tumour regression rates was investigated. The median GTV(init), GTV(res), GTV(res)+ GZ in all patients were 44.4 cm(3), 8.2 cm(3), 20.3 cm(3), respectively. The median R was 78.5% and the median R(GZ) was 50.1%. The histology and FIGO staging showed a significant impact on GTV(init), GTV(res) and GTV(res)+ GZ. Grey zones represent a substantial proportion of the residual tumour volume at the time of brachytherapy. Differentiation of high signal intensity mass and surrounding intermediate signal intensity grey zones may be reasonable.

Metabolic tumour volume and total lesion glycolysis, measured using preoperative 18F-FDG PET/CT, predict the recurrence of endometrial cancer.

PubMed

Shim, S-H; Kim, D-Y; Lee, D-Y; Lee, S-W; Park, J-Y; Lee, J J; Kim, J-H; Kim, Y-M; Kim, Y-T; Nam, J-H

2014-08-01

To investigate the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured by preoperative positron emission tomography and computerised tomography (PET/CT), in women with endometrial cancer. Retrospective cohort study. A tertiary referral centre. Women with endometrial cancer who underwent preoperative (18)F-FDG PET/CT in the period 2004-2009. Clinicopathological data for 84 women with endometrial cancer were reviewed from medical records. Cox proportional hazards modelling identified recurrence predictors. The receiver operating characteristic (ROC) curve was used to determine the cut-off value for predicting recurrence. Disease-free survival (DFS). The number of patients with International Federation of Gynecology and Obstetrics (FIGO) stages were: I (58); II (11); III (13); and IV (2). The median DFS was 48 (1-85) months. By univariate analysis, DFS was significantly associated with FIGO stage, histology, peritoneal cytology, myometrial invasion, nodal metastasis, serum CA-125, MTV, and TLG. Using multivariate analysis, the MTV (P = 0.010; hazard ratio, HR = 1.010; 95% confidence interval, 95% CI = 1.002-1.018) and TLG (P = 0.024; HR = 1.001; 95% CI = 1.000-1.002) were associated with DFS. The area under the ROC curve was 0.679 (95% CI = 0.505-0.836) after discriminating for recurrence using an MTV cut-off value of 17.15 ml. Regarding TLG, the cut-off value was 56.43 g and the area under the ROC plot was 0.661 (95% CI = 0.501-0.827). Kaplan-Meier survival graphs demonstrated a significant difference in DFS between groups categorised using the cut-off values for MTV and TLG (P < 0.022 for MTV and P < 0.047 for TLG, by log-rank test). Preoperative MTV and TLG could be independent prognostic factors predicting the recurrence of endometrial cancer. © 2014 Royal College of Obstetricians and Gynaecologists.

Hematopoietic lineage cell-specific protein 1 immunoreactivity indicates an increased risk of poor overall survival in patients with ovarian carcinoma.

PubMed

Liu, Wenting; Kajiyama, Hiroaki; Shibata, Kiyosumi; Koya, Yoshihiro; Senga, Takeshi; Kikkawa, Fumitaka

2018-06-01

Hematopoietic lineage cell-specific protein 1 (HS1) is a 75-kDa intracellular protein that is expressed primarily in hematopoietic cells. Several previous studies have demonstrated the association between HS1 expression and a poor prognosis in hematopoietic malignancies; however, in solid tumors, no studies not been reported. The present study examined the distribution and expression of HS1 in human epithelial ovarian carcinoma (EOC) to determine its clinical significance. Paraffin sections were obtained from EOC tissues and immunostained with HS1 antibody, and then the staining intensities were evaluated. Overall survival (OS) was determined using the Kaplan-Meier estimator method, and multivariate analysis was performed using the Cox proportional hazards analysis. In total, 195 patients with EOC (median age, 56 years) were enrolled into the present study. HS1 immunoreactivity was categorized based on expression levels: Low (89/195; 45.6%) and high (106/195; 54.4%). Results demonstrated no association between expression level(s) and any clinicopathological parameter including age, International Federation of Gynecology and Obstetrics (FIGO) staging, type of chemotherapy or type of surgery received. The 5-year OS rates of patients who demonstrated low (n=89) and high (n=106) HS1 expression were 90.4 and 66.7%, respectively. The OS times for patients with high HS1 expression were significantly shorter compared with those for patients exhibiting low HS1 expression (P=0.0065). Results obtained from the multivariate analysis demonstrated that the FIGO stage and the amount of HS1 expressed were significant independent prognostic markers for poorer OS (hazard ratio, 3.539; 95% confidence interval, 1.221-12.811; P=0.0187). High HS1 expression levels may serve as a useful biomarker in patients with EOC who are likely to exhibit an unfavorable clinical outcome.

Implementation of laparoscopic hysterectomy for endometrial cancer over the past decade.

PubMed

Wollinga, Tim; Ezendam, Nicole P M; Eggink, Florine A; Smink, Marieke; van Hamont, Dennis; Pijlman, Brenda; Boss, Erik; Robbe, Elisabeth J; Ngo, Huy; Boll, Dorry; Mom, Constantijne H; van der Aa, Maaike A; Kruitwagen, Roy F L P; Nijman, Hans W; Pijnenborg, Johanna M A

2018-01-01

Laparoscopic hysterectomy (LH) for the treatment of early-stage endometrial carcinoma/cancer (EC) has demonstrated to be safe in several randomized controlled trials. Yet, data on implementation of LH in clinical practice are limited. In the present study, implementation of LH for EC was evaluated in a large oncology network in the Netherlands. Retrospectively, a total of 556 EC patients with FIGO stage I-II were registered in the selected years. The proportion of LH gradually increased from 11% in 2006 to 85% in 2015. LH was more often performed in patients with low-grade EC and was not related to the studied patient characteristics. The introduction of TLH was frequently preceded by LAVH. Patients treated in teaching hospitals were more likely to undergo a LH compared to patients in non-teaching hospitals. The conversion rate was 7.7%, and the overall complication rates between LH and AH were comparable, but less postoperative complications in LH. Implementation of laparoscopic hysterectomy for early-stage EC increased from 11 to 85% in 10 years. Implementation of TLH was often preceded by LAVH and was faster in teaching hospitals.

Primary radiotherapy for carcinoma of the endometrium using external beam radiotherapy and single line source brachytherapy.

PubMed

Churn, M; Jones, B

1999-01-01

A small proportion of patients with adenocarcinoma of the endometrium are inoperable by virtue of severe concurrent medical conditions, gross obesity or advanced stage disease. They can be treated with primary radiotherapy with either curative or palliative intent. We report 37 such patients treated mainly with a combination of external beam radiotherapy and intracavitary brachytherapy using a single line source technique. The 5-year disease-specific survival for nonsurgically staged patients was 68.4% for FIGO Stages I and II and 33.3% for Stages III and IV. The incidence of late morbidity was acceptably low. Using the Franco-Italian Glossary, there was 27.0% grade 1 but no grade 2-4 bladder toxicity. For the rectum the rates were 18.9% grade 1, 5.4% grade 2, 2.7% grade 3, and no grade 4 toxicity. Methods of optimizing the dose distribution of the brachytherapy by means of variation of treatment length, radioactive source positions, and prescription point according to tumour bulk and individual anatomy are discussed. The biologically equivalent doses (BED) for combined external beam radiotherapy and brachytherapy were calculated to be in the range of 78-107 Gy(3) or 57-75 Gy(10) at point 'A' and appear adequate for the control of Stage I cancers.

Primary radiation therapy for medically inoperable patients with endometrial carcinoma--stages I-II.

PubMed

Varia, M; Rosenman, J; Halle, J; Walton, L; Currie, J; Fowler, W

1987-01-01

Surgery with or without adjuvant radiation is the established method of treating patients with Stage I and II adenocarcinoma of the endometrium. However, patients who are poor operative risks must be treated with radiation therapy only. We report on 73 such patients treated at the University of North Carolina between 1969 and 1980. All patients had an adenocarcinoma of the endometrium; 41 were FIGO Stage I, 32 Stage II. The minimum follow-up period was 4 years. Life table analysis shows a disease-free survival of 72% at 3 years and 57% at 5 years for Stage I patients. There was a strong correlation between histologic tumor grade and survival in these patients; the 5-year survival for grade 1 was 72%, for grade 2 59%, and for grade 3 31%. The difference between G1 and G3 is significant at the p = .045 level. Coexisting medical conditions were responsible for 12 deaths; almost as many as the 16 cancer-related deaths. Stage II patients have an actuarial disease-free survival of 36% at 3 years and 26% at 5 years, significantly worse than Stage I patients (p = .029 at 3 years). Failures were seen in 16/41 (39%) Stage I and 19/32 (59%) Stage II patients; 29/35 (83%) of these recurrences had component of local/pelvic failure and 15/35 (43%) of the recurrences were local/pelvic only. Specific suggestions on how to improve local therapy for these patients are presented.

Primary mucosal malignant melanoma of the cervix: case report and review of the literature.

PubMed

Cetinkaya, Kadir; Benzer, Emine; Dervisoglu, Haluk

2015-09-09

The incidence of primary mucosal malignant melanoma (PMMM) is 1.3% among all malignant melanomas (MM). Cervical involvement is very rare; the number of cases of cervical PMMM reported so far is around 80. In our patient, a dark color, 2-cm diameter, nonulcerated tumor formation was observed upon examination of the cervix. Tumoral tissue consisted of atypical melanocytic cells containing numerous mitotic figures. In immunochemical studies, S-100, Melan-A, and HMB-45 positivity were observed. The tumor was 20 mm in invasion depth, Breslow IV, and FIGO stage IB1. Radical surgery was followed by adjuvant radiotherapy, and subsequently interferon treatment was applied. Examination and scans 20 months after surgery were free from tumor.

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study

PubMed Central

Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

2015-01-01

Background: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). Results: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Conclusion: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed. PMID:25562434

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a subanalysis of the AGO ROBOT study.

PubMed

Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

2015-02-17

Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.

Initial incomplete surgery modifies prognosis in advanced ovarian cancer regardless of subsequent management.

PubMed

Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona; Herlea, Vlad; David, Leonard; Brasoveanu, Vladislav; Popescu, Irinel

2015-04-01

Prognosis in ovarian cancer is determined by completeness of cytoreduction and proper management by specialized oncological gynecologists. Incomplete initial debulking surgery in non-specialized Centers is, however, a reality and there is ongoing discussion about the best subsequent management of such patients. Patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics--FIGO FIGO stages IIIC-IV) who had biopsy by laparotomy or incomplete cytoreduction followed or not by chemotherapy further referred to our Institution between January 2002 and May 2014 were included. The two groups of incomplete cytoreduction [followed by upfront surgery or followed by chemotherapy and interval debulking surgery (IDS)] were compared and also compared against a cohort of 197 patients with similar characteristics who underwent upfront maximal surgery according to the standard at our Iinstitution during the same period. A total of 99 eligible patients were identified. Sixty-seven of them underwent biopsies by laparotomy and 32 underwent incomplete cytoreduction in other institutions. Twenty-eight patients underwent direct re-operation while 71 patients underwent neoadjuvant chemotherapy followed by IDS. The mean overall survival duration for patients with upfront reoperation was 31 months and 54 months for patients with neoadjuvant chemotherapy and IDS, considerably lower than the 72 months obtained for the group of 197 patients with maximal up-front complete cytoreduction at our Institution. Primary biopsy or incomplete cytoreduction reduces survival regardless of the subsequent approach. However, if incomplete cytoreduction has occurred, neoadjuvant chemotherapy followed by IDS is preferable to up-front reoperation. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Post-operative peritoneal washing cytology in cases of stage IIIa endometrial carcinoma with positive peritoneal cytology].

PubMed

Kato, T; Hirai, Y; Hasumi, K

1995-07-01

According to the new FIGO staging of corpus cancer, the cases with positive peritoneal cytology alone belong in stage IIIa. The authors previously reported, however, good prognosis of IIIa cases with only positive peritoneal cytology. In order to assess the potential of malignant cells in the peritoneal cavity to metastasize, post-operative peritoneal washing cytology was undertaken. This study was conducted on a total of 115 consecutive patients with endometrial carcinoma who underwent primary surgical therapy at the Cancer Institute Hospital during the 25-month period from December, 1991 to December, 1993. Fifteen cases were included in stage IIIa with positive intraoperative peritoneal cytology alone. In 12 cases with endometrioid adenocarcinoma, a Silascon tube was indwelt in the abdominal cavity before closure of the abdomen. The peritoneal cavity was washed with 500 ml of physiological saline through the indwelt tube 14 days after the operation. The cytology of recovered washings was negative in all cases. Only two cases received postoperative chemotherapy owing to other prognostic factors. These 12 cases are alive with no evidence of disease after 12 to 36 months. The present study demonstrated that malignant cells in the peritoneal cavity appear to have a very low potential for implantation into the peritoneum.

Uterine cervix cancer treatment at Radiumhemmet: 90 years′ experience. Time trends of age, stage, and histopathology distribution

PubMed Central

Hellman, Kristina; Hellström, Ann-Cathrin; Pettersson, B Folke

2014-01-01

Since the introduction of screening programs for cervical cancer (CC) the incidence has decreased and CC is discovered at an earlier stage. The purpose of this study was to analyze time trends in age, stage, and histopathology over a 90-year period and to our knowledge this is the largest single institutional series in the literature of invasive cervical carcinoma (CC) cases. This is a retrospective study comprising 18,472 women treated for CC from 1914 until 2004 at Radiumhemmet, Stockholm. The material is part of the international CC statistics published since 1937 in the League of Nations' Annual Reports, and since 1958 under the patronage of International Federation of Gynecology and Obstetrics (FIGO). During the 90-year study period, the annual number of cases treated increased to over 400 up until 1965, after which there was a gradual drop to less than 100 cases in 2004. A pronounced shift toward earlier stages at diagnosis was noted. The mean age at diagnosis increased in all stages, predominantly in advanced stages. A reduction in squamous cell carcinoma (SCC) cases and a sixfold increase in the proportion of adenocarcinoma (AC) cases were observed. The mean age at diagnosis for squamous and AC cases shifted after 1970, when the SCC cases ultimately became 3 years older than the AC cases in contrast to around 1950 when they were 3 years younger than the AC cases. The changes in the distribution by age, stage, and histopathology during this 90-year period are probably associated with: improved social conditions and increased access to health care, the introduction of screening programs for CC in the 1960s, and a change in the risk factors for CC (changed sexual behavior, introduction of contraceptive pills, and changed smoking habits). This is a study on changes in the distribution by age, stage, and histopathology in a large series of cervical cancer treated in Sweden during a 90-year period. It also includes an historical review about the development of staging rules and the international reporting system for gynecological cancers. PMID:24421278

Combined detection of Twist1, Snail1 and squamous cell carcinoma antigen for the prognostic evaluation of invasion and metastasis in cervical squamous cell carcinoma.

PubMed

Yang, Huilun; Hu, Haiyang; Gou, Yanling; Hu, Yuhong; Li, Hui; Zhao, Hongwei; Wang, Beidi; Li, Peiling; Zhang, Zongfeng

2018-04-01

Cervical cancer is one of the most common malignant tumours of the female reproductive system, ranking second only to breast cancer in morbidity worldwide. Essential features of the progression of cervical cancer are invasion and metastasis, which are closely related to disease prognosis and mortality rate. At the present time there is no effective method to evaluate cancer invasion and metastasis before surgery. Here we report our study on molecular changes in biopsy tissue for the prognostic evaluation of cancer invasion and metastasis. Expression of the epithelial-mesenchymal transition-inducing transcription factors Twist1 and Snail1 was detected by immunohistochemistry in 32 normal, 36 low-grade squamous intraepithelial neoplasia (LSIL), 54 high-grade squamous intraepithelial neoplasia (HSIL) and 320 cervical squamous cell carcinoma (CSCC) samples. The correlation between the expression of Twist1, Snail1 and squamous cell carcinoma antigen (SCCA) in CSCC tissues and clinical pathology results was evaluated. A transwell migration and invasion assay was used to explore the roles of Twist1 and Snail1 in the invasion of cancer cells. Lymph node metastasis and lymphovascular space invasion (LVSI) rates for the following groups were analysed: SCCA(+) group, Twist1(+) group, Snail1(+) group, Twist1(+)Snail1(+)group, Twist1(+)SCCA(+)group, Snail1(+)SCCA(+)group and Twist1(+)Snail1(+)SCCA(+) group. The expression of Twist1 and Snail1 was significantly upregulated in HSIL and CSCC (p < 0.05). Twist1 and Snail1 expression levels were associated with LVSI, lymph node metastasis and histological grade (p < 0.05) but not with age or FIGO stage (p > 0.05). The expression of SCCA was associated with LVSI, lymph node metastasis, FIGO stage and histological grade (p < 0.05) but not with age (p > 0.05). Twist1 was an independent factor contributing to the invasion ability of cervical cancer cells. In addition, the positive rate of lymph node metastasis and LVSI was higher in the Twist1(+)Snail1(+)SCCA(+) group than in the SCCA(+) group, Twist1(+) group and Snail1(+) group, respectively (p < 0.05). Combined detection of Twist1 and Snail1 in SCCA-positive biopsy specimens may be a potential method for evaluating the invasion and metastasis of CSCC prior to surgery.

[Ultrasound semiotics in recurrent ovarian cancer after optimal cytoreductive surgery].

PubMed

Baklanova, N S; Kolomiets, L A; Frolova, I G; Viatkina, N V; Krasil'nikov, S É

2014-01-01

Features of ultrasound picture of morphologically verified recurrence of ovarian cancer in 21 patients are presented, who received combined treatment including cytoreductive surgery in the form of hysterectomy with oophorectomy, resection of the greater omentum and 6 courses of chemotherapy CAP for ovarian cancer stage III (FIGO). In all patients cytoreductive surgery was optimal--without residual tumor. Recurrence of the disease was detected in 12-48 months in 80.9% of the cases. Three variants of recurrence was revealed by ultrasonography: isolated peritoneal dissemination, in 14.2% of the cases, which was mainly detected during the first 12 months; single entities in the projection of the small pelvis (61.9%) and mixed form (local lesions of small pelvis and peritoneal dissemination) in 23.8% of the cases.

Integrated external and interstitial radiation therapy for primary carcinoma of the vagina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Puthawala, A.; Syed, A.M.; Nalick, R.

1983-09-01

Twenty-seven patients with the diagnosis of primary carcinoma of the vagina were treated by definitive radiotherapy. Twenty-three patients received a combination of external and interstitial iridium-192 implant irradiation and four patients received only interstitial irradiation. Twenty-one patients had squamous cell carcinoma and six had adenocarcinoma. All patients were staged according to the FIGO classification. More than 70% of patients had relatively advanced local disease and conventional intracavitary irradiation was unsuitable. Local tumor control was observed in 85% (23 of 27 patients), and 56% of the patients remain alive and free of disease for a median follow-up period of 50 monthsmore » to a maximum follow-up period of 84 months. Fifteen percent of the patients suffered from treatment-related complications.« less

Gestational trophoblastic disease.

PubMed

Soper, John T

2006-07-01

This review summarizes the primary management of molar pregnancies, surveillance after evacuation, and the evaluation and management of malignant gestational trophoblastic neoplasia (GTN). Most women with gestational trophoblastic disease can be successfully managed with preservation of their normal reproductive function. It is important to manage molar pregnancies properly to minimize acute complications and identify malignant sequelae promptly. Current International Federation of Gynecology and Obstetrics (FIGO) guidelines for making the diagnosis and staging of GTN allow uniformity for reporting results of treatment. It is important to individualize treatment for women with malignant GTN based upon risk factors, using less toxic therapy for patients with low-risk disease and aggressive multiagent therapy for those with high-risk disease. Patients with malignant GTN should be managed in consultation with an individual experienced in the complex, multimodality treatment of these patients.

Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer

PubMed Central

Signorelli, Mauro; Lissoni, Andrea Alberto; De Ponti, Elena; Grassi, Tommaso; Ponti, Serena

2015-01-01

Objective Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC). Methods Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study. Results Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis. Conclusion Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III. PMID:26197768

Hysteroscopic Myomectomy of FIGO Type 2 Leiomyomas Under Local Anesthesia: Bipolar Radiofrequency Needle-Based Release Followed By Electromechanical Morcellation.

PubMed

Munro, Malcolm G

2016-01-01

To demonstrate a technique designed to expand the capabilities of hysteroscopic intrauterine morcellators to deep type 1 and type 2 lesions. The technique comprises "release" of the tumor using a bipolar radiofrequency needle, followed by dissection and extraction with an electromechanical morcellator, all under local anesthesia. Description of technique using images and video (Canadian Task Force classification Class III). Office uterine procedure and imaging center; academic medical center. Following the administration of local anesthesia and access to the endometrial cavity with a 5.5-mm-o.d. hysteroscopic sheath with a 5 Fr operative channel, a 5 Fr bipolar needle electrode system is used to circumscribe the leiomyoma and enter the pseudocapsule, thereby "releasing" the lesion. Blunt dissection is performed as appropriate and then the system is switched to a hysteroscopic morcellating system (MyoSure; Hologic, Bedford, MA), which is then used to further dissect and remove the target lesion with electromechanical morcellation. The development of intrauterine morcellators has facilitated the performance of hysteroscopic myomectomy, especially under local anesthesia, but the side aperture-based design of the systems limits their use in International Federation of Gynecology and Obstetrics (FIGO) type 1 and 2 tumors, particularly those located at the uterine fundus. This technique, based in part on a previously published technique of leiomyoma release, improves access of the electromechanical morcellator to leiomyomas that previously were inaccessible, and minimizes myometrial trauma by dissecting the tumor via the relatively avascular pseudocapsule. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Prognostic value of estrogen receptor and progesterone receptor tumor expression in Danish ovarian cancer patients: from the 'MALOVA' ovarian cancer study.

PubMed

Høgdall, Estrid V S; Christensen, Lise; Høgdall, Claus K; Blaakaer, Jan; Gayther, Simon; Jacobs, Ian J; Christensen, Ib Jarle; Kjaer, Susanne K

2007-11-01

Estrogen and progesterone are important hormones secreted by the ovary acting through specific receptors. Tumor tissue expression profiles of these have demonstrated prognostic value in malignancies such as breast, uterine and prostate cancer. In this study, including tissue samples from 773 Danish patients with an ovarian tumor, we evaluated whether estrogen receptor (ER) and progesterone receptor (PR) expression correlated with clinico-pathological parameters, and a possible prognostic impact on ovarian cancer (OC) patients was investigated. Using tissue array and immunohistochemistry, we analyzed the ER and PR expression levels in tissues from 582 women with OC and 191 women with low malignancy potential (LMP) ovarian tumors. Our results demonstrated that ER was expressed in 30 of the 191 LMP tumors (16%) and in 207 of the 582 OC (36%). PR was expressed in 38 LMP tumors (20%) and in 115 OC (20%). For both tumor types an excess of positive tumors was found in the serous compared to the mucinous subtype (p< or =0.00001). The frequency of ER expression-positive OC increased with increasing FIGO stage (p=0.0003), and the frequency of PR-positive tumors increased with increasing histological grade (p=0.0006). In a Cox survival analysis, a tissue ER and PR expression 10% or higher was found to imply an independent significant advantageous course of patient disease-specific survival (ER: hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.63-0.99; PR: HR, 0.69; 95% CI, 0.51-0.94) together with FIGO stage, residual tumor after primary surgery, age at diagnosis and other histological types vs. serous adenocarcinoma. The histological grade of tumor was found to have no independent prognostic value. The prognostic value of ER and PR was found additive with a HR for patients with high ER and PR expression of 0.48 (95% CI, 0.31-0.74) compared to patients with <10% expression for both receptors. In conclusion, our results predict that an elevated expression of ER and PR, alone and in combination, point to a favorable outcome for patients with OC.

Downregulation of SASH1 correlates with tumor progression and poor prognosis in ovarian carcinoma

PubMed Central

REN, XIAOYAN; LIU, YIFEI; TAO, YUMEI; ZHU, GUOXIANG; PEI, MEILAN; ZHANG, JIANGUO; LIU, JIAN

2016-01-01

SAM- and SH3-domain containing 1 (SASH1) is a recently identified tumor suppressor gene that is required in the tumorigenesis of breast and other solid carcinomas. The SASH1 protein contains SH3 and SAM domains, indicating that it may serve an important role in intracellular signal transduction. The purpose of the present study was to investigate the expression of SASH1 in ovarian carcinoma and the correlation between its expression with clinical pathological features and clinical significance, and the effect of SASH1 on cell proliferation, apoptosis and migration of ovarian SKOV3 cells. The human ovarian carcinoma tissues and adjacent normal tissues were collected following surgery. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression levels of SASH1 mRNA and protein, respectively. The expression levels of SASH1 mRNA and protein in ovarian carcinoma tissues were significantly lower than that observed in adjacent normal tissues (P<0.05). The expression levels of SASH1 in samples from patients without lymph nodes metastasis and patients with early FIGO stage was lower than those with lymph nodes metastasis and patients with advanced FIGO stage (P<0.05). Flow cytometry analysis and Transwell invasion chamber experiments were used to investigate the effect of SASH1 on the cell proliferation, apoptosis and migration of SKOV3 cells. The recombinant plasmid pcDNA3.1-SASH1 was constructed and transfected into SKOV3 cells. In addition, the SKOV3 cells in the pcDNA3.1-SASH1 group exhibited significantly reduced cell growth, proliferation, and migration ability compared to the empty vector group and normal group (P<0.01). There were a greater number of apoptotic cells in the pcDNA3.1-SASH1 group compared to the empty vector group and normal group (P<0.01). Taken together, these results indicated that SASH1 may be a tumor suppressor gene in ovarian carcinoma, and SASH1 expression inhibited growth, proliferation and migration, and enhanced apoptosis of SKOV3 cells. PMID:27123075

Downregulation of SASH1 correlates with tumor progression and poor prognosis in ovarian carcinoma.

PubMed

Ren, Xiaoyan; Liu, Yifei; Tao, Yumei; Zhu, Guoxiang; Pei, Meilan; Zhang, Jianguo; Liu, Jian

2016-05-01

SAM- and SH3-domain containing 1 (SASH1) is a recently identified tumor suppressor gene that is required in the tumorigenesis of breast and other solid carcinomas. The SASH1 protein contains SH3 and SAM domains, indicating that it may serve an important role in intracellular signal transduction. The purpose of the present study was to investigate the expression of SASH1 in ovarian carcinoma and the correlation between its expression with clinical pathological features and clinical significance, and the effect of SASH1 on cell proliferation, apoptosis and migration of ovarian SKOV3 cells. The human ovarian carcinoma tissues and adjacent normal tissues were collected following surgery. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression levels of SASH1 mRNA and protein, respectively. The expression levels of SASH1 mRNA and protein in ovarian carcinoma tissues were significantly lower than that observed in adjacent normal tissues (P<0.05). The expression levels of SASH1 in samples from patients without lymph nodes metastasis and patients with early FIGO stage was lower than those with lymph nodes metastasis and patients with advanced FIGO stage (P<0.05). Flow cytometry analysis and Transwell invasion chamber experiments were used to investigate the effect of SASH1 on the cell proliferation, apoptosis and migration of SKOV3 cells. The recombinant plasmid pcDNA3.1-SASH1 was constructed and transfected into SKOV3 cells. In addition, the SKOV3 cells in the pcDNA3.1-SASH1 group exhibited significantly reduced cell growth, proliferation, and migration ability compared to the empty vector group and normal group (P<0.01). There were a greater number of apoptotic cells in the pcDNA3.1-SASH1 group compared to the empty vector group and normal group (P<0.01). Taken together, these results indicated that SASH1 may be a tumor suppressor gene in ovarian carcinoma, and SASH1 expression inhibited growth, proliferation and migration, and enhanced apoptosis of SKOV3 cells.

FDG uptake heterogeneity in FIGO IIb cervical carcinoma does not predict pelvic lymph node involvement.

PubMed

Brooks, Frank J; Grigsby, Perry W

2013-12-23

Many types of cancer are located and assessed via positron emission tomography (PET) using the 18F-fluorodeoxyglucose (FDG) radiotracer of glucose uptake. There is rapidly increasing interest in exploiting the intra-tumor heterogeneity observed in these FDG-PET images as an indicator of disease outcome. If this image heterogeneity is of genuine prognostic value, then it either correlates to known prognostic factors, such as tumor stage, or it indicates some as yet unknown tumor quality. Therefore, the first step in demonstrating the clinical usefulness of image heterogeneity is to explore the dependence of image heterogeneity metrics upon established prognostic indicators and other clinically interesting factors. If it is shown that image heterogeneity is merely a surrogate for other important tumor properties or variations in patient populations, then the theoretical value of quantified biological heterogeneity may not yet translate into the clinic given current imaging technology. We explore the relation between pelvic lymph node status at diagnosis and the visually evident uptake heterogeneity often observed in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images of cervical carcinomas. We retrospectively studied the FDG-PET images of 47 node negative and 38 node positive patients, each having FIGO stage IIb tumors with squamous cell histology. Imaged tumors were segmented using 40% of the maximum tumor uptake as the tumor-defining threshold and then converted into sets of three-dimensional coordinates. We employed the sphericity, extent, Shannon entropy (S) and the accrued deviation from smoothest gradients (ζ) as image heterogeneity metrics. We analyze these metrics within tumor volume strata via: the Kolmogorov-Smirnov test, principal component analysis and contingency tables. We found no statistically significant difference between the positive and negative lymph node groups for any one metric or plausible combinations thereof. Additionally, we observed that S is strongly dependent upon tumor volume and that ζ moderately correlates with mean FDG uptake. FDG uptake heterogeneity did not indicate patients with differing prognoses. Apparent heterogeneity differences between clinical groups may be an artifact arising from either the dependence of some image metrics upon other factors such as tumor volume or upon the underlying variations in the patient populations compared.

Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Anne, E-mail: akim2@health-quest.org; Schreiber, David; Rineer, Justin

2011-11-15

Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: Wemore » identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.« less

Relationship between race and clinical characteristics, extent of disease, and response to chemotherapy in patients with low-risk gestational trophoblastic neoplasia.

PubMed

Maestá, Izildinha; Berkowitz, Ross S; Goldstein, Donald P; Bernstein, Marilyn R; Ramírez, Luz Angela C; Horowitz, Neil S

2015-07-01

To evaluate the potential effects of race on clinical characteristics, extent of disease, and response to chemotherapy in women with postmolar low-risk gestational trophoblastic neoplasia (GTN). This non-concurrent cohort study was undertaken including patients with FIGO-defined postmolar low-risk GTN treated with comparable doses and schedules of chemotherapy at the New England Trophoblastic Disease Center (NETDC) between 1973 and 2012. Racial groups investigated included whites, African American and Asians. Information on patient characteristics and response to chemotherapy (need for second line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles/regimens, need for combination chemotherapy, and time to hCG remission) was obtained. Of 316 women, 274 (86.7%) were white, 19 (6%) African American, and 23 (7.3%) Asian. African Americans were significantly younger than white and Asian women (p=0.008). Disease presentation, and extent of disease, including antecedent molar histology, median time to persistence, median hCG level at persistence, rate of D&C at persistence, presence of metastatic disease, and FIGO stage and risk score were similar among races. Need for second line chemotherapy (p=0.023), and median number of regimens (p=0.035) were greater in Asian women than in other races. Low-risk GTN was more aggressive in Asian women, who were significantly more likely to need second line chemotherapy and a higher number of chemotherapy regimens to achieve complete remission than women of African American and Asian descent. Further studies involving racial differences related to clinical, biological and environmental characteristics are needed. Copyright © 2015. Published by Elsevier Inc.

Racial differences in patients with adenocarcinoma of the endometrium.

PubMed

Cronjé, H S; Fourie, S; Doman, M J; Helms, J B; Nel, J T; Goedhals, L

1992-11-01

To determine the differences between white and black women with regard to the presentation and behavior of adenocarcinoma of the endometrium. Records of 273 (68%) white patients and 117 (32%) black patients with endometrial adenocarcinoma were reviewed in Bloemfontein, South Africa. Survival data was calculated according to the direct method where losses in follow-up were regarded as tumor deaths. Most patients (82%) were treated by pre-operative radium followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with post-operative external irradiation where indicated. Pre-operatively, fewer black women had reached FIGO stage I, while a larger number had advanced to stages II-IV (P = 0.0024). In addition, the tumor differentiation was more often poor in the black group (P < 0.0001). Ten-year follow-up was achieved in 84% of the white patients and 51% of the black patients and the 10-year survival figures were 67% for white patients and 28% for blacks (P < 0.0001). Endometrial adenocarcinoma is a more aggressive disease in black women than it is in whites.

Neuroendocrine Neoplasms of the Ovary: A Retrospective Study of the North Eastern German Society of Gynecologic Oncology (NOGGO).

PubMed

Sehouli, Jalid; Woopen, Hannah; Pavel, Marianne; Richter, Rolf; Lauterbach, Lisa-Kathrin; Taube, Eliane; Darb-Esfahani, Silvia; Fotopoulou, Christina; Pietzner, Klaus

2016-03-01

Neuroendocrine neoplasms (NEN) of the female genital tract account for 2% of gynecological cancers. The aim of this study was to share our experience of 11 primary neuroendocrine neoplasms of the ovary. All patients who presented and/or were treated at our Institution with histologically-confirmed NEN of the ovary were included. Clinical data including tumor stage, diagnostic and therapeutic management and survival were assessed. Pathological specimens were critically reviewed. We identified 11 patients with NEN of the ovary consisting of nine neuroendocrine cancers and two carcinoids. Median age was 55.9 years. NEN were mostly poorly differentiated (72.4%). Primary surgery was performed in all patients. Adjuvant chemotherapy was administered in five patients consisting of platinum-based regimens. Median overall survival was 20 months. We propose a diagnostic algorithm for NEN of the ovary and discuss possible treatments according to FIGO stages. Patients should be included in multicenter studies whenever possible. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality.

PubMed

Anglesio, Michael S; Wang, Yi Kan; Maassen, Madlen; Horlings, Hugo M; Bashashati, Ali; Senz, Janine; Mackenzie, Robertson; Grewal, Diljot S; Li-Chang, Hector; Karnezis, Anthony N; Sheffield, Brandon S; McConechy, Melissa K; Kommoss, Friedrich; Taran, Florin A; Staebler, Annette; Shah, Sohrab P; Wallwiener, Diethelm; Brucker, Sara; Gilks, C Blake; Kommoss, Stefan; Huntsman, David G

2016-06-01

Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

PubMed

Nasu, K; Okamoto, M; Nishida, M; Takai, N; Narahara, H

2012-01-01

Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report.

PubMed

Suwannarurk, Komsun; Thaweekul, Yudthadej; Mairaing, Karicha; Poomtavorn, Yenrudee; Tangtiang, Kaan; Piyawang, Wichet; Bhamarapravatana, Kornkarn

2015-04-01

Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growthfactor (VEGF), has been approvedfor concurrent treatment with first line chemotherapy in advanced epithelial ovarian cancer. A case of an advanced stage epithelial ovarian cancer (EOC) receiving a combination of bevacizumab, carboplatin andpaclitaxel chemotherapy was reported. A 44-year-old woman was presented with abdominal discomfort and distention for 4 months. Bilateral 12 cm diameter ovarian tumors were diagnosed as FIGO stage IIIc after surgical staging operation. Histopathology report showed the mixed type of serous and endometriod adenocarcinoma. The patient was then started on carboplatin/paclitaxel combination chemotherapy for 6 cycles after surgery every 3 weeks. Bevacizumab (7.5 mg/ m2) was concurrently administered with chemotherapy every 3 weeks startingfrom the 2nd cycle. A complete remission was achieved after the end of the chemotherapy treatment. Bevacizumab was continued for one year after the completion of the standard chemotherapy. Bone marrow suppression, hypertension and proteinuria were not found during Bevacizumab treatment. At bevacizumab treatment completion, a platinum-sensitive recurrent ovarian cancer was diagnosed at the two weeks postprogram routine check-up. The patient was counseled to start second line chemotherapy treatment and has yet to come back with her decision. Combination of bevacizumab, carboplatin and paclitaxelfor first line chemotherapy in advanced EOC in this case had no serious side effects and need further study.

The G protein-coupled estrogen receptor (GPER/GPR30) may serve as a prognostic marker in early-stage cervical cancer.

PubMed

Friese, Klaus; Kost, Bernd; Vattai, Aurelia; Marmé, Frederik; Kuhn, Christina; Mahner, Sven; Dannecker, Christian; Jeschke, Udo; Heublein, Sabine

2018-01-01

Estrogen signalling is transmitted via various receptors and multiple intracellular signalling pathways. Estrogen receptor alpha (ERα)-mediated transcription of target genes has been demonstrated to be closely linked to human papilloma virus (HPV)-induced carcinogenesis in case of cervical cancer. So far, the role of non-genomic estrogen signals in cervical cancer, e.g. transmitted by the G protein-coupled estrogen receptor (GPER) remains to be rather elusive. Today's knowledge on the role of GPER in cervical cancer is sparse and-to the best of our knowledge-GPER has not been investigated in context with clinicopathological parameters or prognosis of cervical cancer. Therefore, the current study investigated whether GPER is expressed in cervical cancer tissue. Further, GPER was correlated to clinicopathological parameters, tissue markers of cervical carcinogenesis and to patient overall and recurrence-free survival. Cervical cancer tissue was collected from 156 patients during surgery between 1993 and 2002. GPER immunostaining was performed on all the cases and correlated to clinicopathological data. More than half of all patients were diagnosed at advanced stage (FIGO II-IV 93/156; 59.6%) of disease. The large majority of patients presented with tumours of intermediate or high grade (G2-3 140/152, 92.1%). 22 cervical cancer-related deaths (22/156, 14.1%) were documented during the follow-up period. GPER was detected in various subcellular staining patterns. In 129/156 (82.7%) cases GPER was expressed in the tumour cell cytoplasm (GPER cyt ). GPER immunopositivity at the cell membrane (GPER mem ) was found in 114/156 (73.1%) cases. While co-occurrence of both membrane and cytoplasmic staining (GPER cyt  + GPER mem ) was detected in the majority of tissue samples (101/156; 64.7%), only few cases (14/156, 9.0%) were classified as not expressing GPER at all. GPER cyt was positively correlated with tumour grade. Statistical associations of GPER and both p16 and p53 were detected. Finally, immunopositivity of GPER cyt was predictive for favourable overall as well as recurrence-free survival in cervical cancer of early stage (FIGO I). This retrospective study reports GPER cyt to be associated with improved overall and recurrence-free survival in early-stage cervical cancer. Further investigations are needed thus to determine whether this observation may be of clinical impact. Interestingly, Raloxifene-a GPER-activating selective estrogen receptor modulator-has recently been demonstrated to be preventive for cervical cancer relapse in mice. Whether this effect is only reliant on raloxifene blocking ERα or may also be related to activation of GPER remains to be determined.

Information Theory to Probe Intrapartum Fetal Heart Rate Dynamics

NASA Astrophysics Data System (ADS)

Granero-Belinchon, Carlos; Roux, Stéphane; Abry, Patrice; Doret, Muriel; Garnier, Nicolas

2017-11-01

Intrapartum fetal heart rate (FHR) monitoring constitutes a reference tool in clinical practice to assess the baby health status and to detect fetal acidosis. It is usually analyzed by visual inspection grounded on FIGO criteria. Characterization of Intrapartum fetal heart rate temporal dynamics remains a challenging task and continuously receives academic research efforts. Complexity measures, often implemented with tools referred to as \\emph{Approximate Entropy} (ApEn) or \\emph{Sample Entropy} (SampEn), have regularly been reported as significant features for intrapartum FHR analysis. We explore how Information Theory, and especially {\\em auto mutual information} (AMI), is connected to ApEn and SampEn and can be used to probe FHR dynamics. Applied to a large (1404 subjects) and documented database of FHR data, collected in a French academic hospital, it is shown that i) auto mutual information outperforms ApEn and SampEn for acidosis detection in the first stage of labor and continues to yield the best performance in the second stage; ii) Shannon entropy increases as labor progresses, and is always much larger in the second stage;iii) babies suffering from fetal acidosis additionally show more structured temporal dynamics than healthy ones and that this progressive structuration can be used for early acidosis detection.

Evaluation of the response of concurrent high dose rate intracavitary brachytherapy with external beam radiotherapy in management of early stage carcinoma cervix.

PubMed

Patidar, Arvind Kumar; Kumar, H S; Walke, Rahul V; Hirapara, Pushpendra H; Jakhar, Shankar Lal; Bardia, M R

2012-10-01

To evaluate local disease control and early complications of concomitant brachytherapy with external beam-radiotherapy in early stage carcinoma cervix. Fifty patients of early stage carcinoma cervix (FIGO-IB/IIA) were randomly divided into study group concomitant external beam irradiation (EBRT) and HDR-ICBT (intra-cavitary brachytherapy, xrt = 50 Gy/25 Fr, HDR 5.2 Gy*5 Fr) and the control group EBRT followed by HDR-ICBT (xrt = 50 Gy/25 Fr, HDR 7.5 Gy*3 Fr). Acute reactions and local disease response were compared between treatment and at 6-month follow up. Median overall treatment times were 38 and 61 days in the study and the control groups, respectively. Acute skin reactions and diarrhea were more in the study but manageable. At the completion of the study, there were 80 and 68 % complete responses, 16 and 20 % partial responses, 0 and 8 % stable diseases in the study group and the control group, respectively. Response was better in the study group but statistically insignificant. Larger number of patients and longer follow up are required to arrive at concrete conclusion.

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

[Malignant tumors of the female genital track in the elderly].

PubMed

Gottwald, Leszek; Akoel, Kindah Mo; Wójcik-Krowiranda, Katarzyna; Bieńkiewicz, Andrzej

2003-09-01

In senium the increase in the incidence of most malignant neoplasms, as well as gynecological cancers is found. In this period of life the vast number of women do not apply for the preventive and follow-up examinations, which increases the number of malignant diseases diagnosed at advanced clinical stages. The coexisting another diseases often limits the possibility of the operative treatment in those cases. To assess the profile of malignant tumors of the genital tract and their treatment in women above 70 year old. 61 women aged from 71 yrs. to 88 yrs. treated operatively between 1997-2001 due to gynecological cancers were included into the study. The structure and detectability of the neoplasms, as well as the type of performed surgical procedures were analysed. 30 endometrial cancers (49.2%), 16 ovarian cancers (26.2%), 14 vulvar cancers (22.9%) and 1 cervical cancer were diagnosed and surgically treated. The endometrial cancer stage I was detected in 18 cases, stage II in 4 cases and stage III in 8 cases. In each case the radical operation was done (total hysterectomy, lymphadenectomy and appendectomy). The ovarian cancer stage I was detected in 3 cases, stage II in 2 cases, stage III in 5 cases, and stage IV in 6 cases. Only in 5 cases out of this group the radical surgery was performed (total hysterectomy, omentectomy and appendectomy). The vulvar cancer stage I was detected in 2 cases, stage II in 11 cases, and FIGO stage III in 4 cases. In each of these women the vulva and bilateral inguinal lymph nodes were resected, and in 2 cases additionally at the same time the Miles operation was performed. The cervical cancer clinical stage I was detected, and the Wertheim operation was performed. The most often diagnosed malignant neoplasm in women above 70 yrs. was the endometrial cancer. The worst first-time diagnosis structure was observed in the ovarian cancer, what significantly decreased the ability of surgical treatment in this group.

Concurrent Chemoradiotherapy With Paclitaxel and Nedaplatin Followed by Consolidation Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix: Preliminary Results of a Phase II Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Meiqin, E-mail: pianozmq@hotmail.co; Liu Suping; Wang, Xiang-E.

Purpose: To evaluate the efficacy and toxicities of concurrent chemoradiotherapy (CCRT) and consolidation chemotherapy in patients with locally advanced squamous cell cervical carcinoma. Methods and Materials: Patients with LASCC (FIGO Stage IIB-IIIB) were treated with pelvic external beam radiotherapy (45 Gy for Stage IIB and 50 Gy for Stage III) and high-dose-rate intracavitary brachytherapy (50 Gy for Stage IIB and 35 Gy for Stage III). The cumulative dose at point A was 50 Gy for Stage IIB and 65 Gy for Stage III. Concurrent chemotherapy with paclitaxel (35 mg/m{sup 2}) and nedaplatin (20 mg/m{sup 2}) was given every week formore » 6 weeks. Consolidation chemotherapy with paclitaxel (135 mg/m{sup 2}) and nedaplatin (60 mg/m{sup 2}) was administered every 3 weeks for 4 cycles. Results: All patients completed CCRT, and 28 of 34 patients completed consolidation chemotherapy. The complete response rate was 88% (95% CI, 73-96%). The most common Grade 3 or higher toxicities were leukopenia/neutropenia (10.9% of the cycles). During a median follow up of 23 months (range, 14-30 months), 5 patients had locoregional failure and 1 patient had distant metastasis. The estimated 2-year progression-free survival and overall survival were 82% (95% CI, 68-95%) and 93% (95% CI, 83-100%), respectively. Grade 3 late complications occurred in 3 patients (9%). Conclusions: CCRT with paclitaxel and nedaplatin followed by consolidation chemotherapy is well tolerated and effective in patients with locally advanced squamous cell cervical carcinoma. Further randomized trials of comparing this regimen with the standard treatment are worth while.« less

A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group.

PubMed

Pautier, P; Floquet, A; Gladieff, L; Bompas, E; Ray-Coquard, I; Piperno-Neumann, S; Selle, F; Guillemet, C; Weber, B; Largillier, R; Bertucci, F; Opinel, P; Duffaud, F; Reynaud-Bougnoux, A; Delcambre, C; Isambert, N; Kerbrat, P; Netter-Pinon, G; Pinto, N; Duvillard, P; Haie-Meder, C; Lhommé, C; Rey, A

2013-04-01

There is no proven benefit of adjuvant treatment of uterine sarcoma (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an increase ≥ 20% of 3-year PFS. Patients with FIGO stage ≤ III US, physiological age ≤ 65 years; chemotherapy: four cycles of doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/day d1-2, cisplatin 75 mg/m² d3, (API) + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%), febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B. The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). API adjuvant CT statistically increases the 3 year-DFS of patients with US.

Expression loss and revivification of RhoB gene in ovary carcinoma carcinogenesis and development.

PubMed

Liu, Yingwei; Song, Na; Ren, Kexing; Meng, Shenglan; Xie, Yao; Long, Qida; Chen, Xiancheng; Zhao, Xia

2013-01-01

RhoB, a member of small GTPases belonging to the Ras protein superfamily, might have a suppressive activity in cancer progression. Here, expression of RhoB gene was evaluated in human benign, borderline and malignant ovary tumors by immunostaining, with normal ovary tissue as control. Malignant tumors were assessed according to Federation Internationale de Gynecologie Obstetrique (FIGO) guidelines and classified in stage I-IV. Revivification of RhoB gene was investigated by analyzing the effect of histone deacetylase (HDAC) inhibitor trichostatin (TSA) and methyltransferase inhibitor 5-azacytidine (5-Aza) on ovarian cancer cells via RT-PCR and western blot. Apoptosis of ovary cancer cells was detected using flowcytometry and fluorescence microscopy. Subsequently, RhoB expression is detected in normal ovary epithelium, borderline tumors, and decreases significantly or lost in the majority of ovarian cancer specimen (P<0.05). RhoB expression decreases significantly from stage II (71.4%) to stage III (43.5%) to stage IV (18.2%, P<0.05). TSA can both significantly revive the RhoB gene and mediate apoptosis of ovarian cancer cells, but 5-Aza couldn't. Interference into Revivification of RhoB gene results in reduction of ovary carcinoma cell apoptosis. It is proposed that loss of RhoB expression occurs frequently in ovary carcinogenesis and progression and its expression could be regulated by histone deacetylation but not by promoter hypermethylation, which may serve as a prospective gene treatment target for the patients with ovarian malignancy not responding to standard therapies.

Expression Loss and Revivification of RhoB Gene in Ovary Carcinoma Carcinogenesis and Development

PubMed Central

Liu, Yingwei; Song, Na; Ren, Kexing; Meng, Shenglan; Xie, Yao; Long, Qida; Chen, Xiancheng; Zhao, Xia

2013-01-01

RhoB, a member of small GTPases belonging to the Ras protein superfamily, might have a suppressive activity in cancer progression. Here, expression of RhoB gene was evaluated in human benign, borderline and malignant ovary tumors by immunostaining, with normal ovary tissue as control. Malignant tumors were assessed according to Federation Internationale de Gynecologie Obstetrique (FIGO) guidelines and classified in stage I-IV. Revivification of RhoB gene was investigated by analyzing the effect of histone deacetylase (HDAC) inhibitor trichostatin (TSA) and methyltransferase inhibitor 5-azacytidine (5-Aza) on ovarian cancer cells via RT-PCR and western blot. Apoptosis of ovary cancer cells was detected using flowcytometry and fluorescence microscopy. Subsequently, RhoB expression is detected in normal ovary epithelium, borderline tumors, and decreases significantly or lost in the majority of ovarian cancer specimen (P<0.05). RhoB expression decreases significantly from stage II (71.4%) to stage III (43.5%) to stage IV (18.2%, P<0.05). TSA can both significantly revive the RhoB gene and mediate apoptosis of ovarian cancer cells, but 5-Aza couldn’t. Interference into Revivification of RhoB gene results in reduction of ovary carcinoma cell apoptosis. It is proposed that loss of RhoB expression occurs frequently in ovary carcinogenesis and progression and its expression could be regulated by histone deacetylation but not by promoter hypermethylation, which may serve as a prospective gene treatment target for the patients with ovarian malignancy not responding to standard therapies. PMID:24223801

Nomogram for suboptimal cytoreduction at primary surgery for advanced stage ovarian cancer.

PubMed

Gerestein, Cornelis G; Eijkemans, Marinus J; Bakker, Jeanette; Elgersma, Otto E; van der Burg, Maria E L; Kooi, Geertruida S; Burger, Curt W

2011-11-01

Maximal cytoreduction to minimal residual tumor is the most important determinant of prognosis in patients with advanced stage epithelial ovarian cancer (EOC). Preoperative prediction of suboptimal cytoreduction, defined as residual tumor >1 cm, could guide treatment decisions and improve counseling. The objective of this study was to identify predictive computed tomographic (CT) scan and clinical parameters for suboptimal cytoreduction at primary cytoreductive surgery for advanced stage EOC and to generate a nomogram with the identified parameters, which would be easy to use in daily clinical practice. Between October 2005 and December 2008, all patients with primary surgery for suspected advanced stage EOC at six participating teaching hospitals in the South Western part of the Netherlands entered the study protocol. To investigate independent predictors of suboptimal cytoreduction, a Cox proportional hazard model with backward stepwise elimination was utilized. One hundred and fifteen patients with FIGO stage III/IV EOC entered the study protocol. Optimal cytoreduction was achieved in 52 (45%) patients. A suboptimal cytoreduction was predicted by preoperative blood platelet count (p=0.1990; odds ratio (OR)=1.002), diffuse peritoneal thickening (DPT) (p=0.0074; OR=3.021), and presence of ascites on at least two thirds of CT scan slices (p=0.0385; OR=2.294) with a for-optimism corrected c-statistic of 0.67. Suboptimal cytoreduction was predicted by preoperative platelet count, DPT and presence of ascites. The generated nomogram can, after external validation, be used to estimate surgical outcome and to identify those patients, who might benefit from alternative treatment approaches.

Primary Fallopian Tube Carcinoma: A Case Report and Literature Review.

PubMed

Rexhepi, Meral; Trajkovska, Elizabeta; Ismaili, Hysni; Besimi, Florin; Rufati, Nagip

2017-06-15

Primary fallopian tube carcinoma (PFTC) is a rare tumour of the female genital tract with an incidence of 0.1-1.8% of all genital malignancies, and it is very difficult to diagnose preoperatively, because of its non-specific symptomatology. In most cases, it is an intraoperative finding or a histopathological diagnosis. It is a tumour that histologically and clinically resembles epithelial ovarian cancer. We are reporting a case of a 62-year-old, postmenopausal women with primary fallopian tube carcinoma of the right fallopian tube in stage IA. The patient has lower abdominal pain, watery vaginal discharge and repeated episodes of bleeding from the vagina. The clinical and radiological findings suggested a right adnexal tumour with elevated CA-125 levels. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and peritoneal washing were performed. Pathologic confirmation of primary serous cystadenocarcinoma of the right fallopian tube was made. Peritoneal washings were negative for malignancy. FIGO stage was considered as IA, and the patient received no courses of chemotherapy and postoperative radiation because she refused it. Ten months after initial surgery, the patient is alive and in good condition. Cytoreduction surgery followed by adequate cycles of chemotherapy is an important strategy to improve patients' prognosis.

[Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

PubMed

Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

2017-01-25

Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t -tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found ( P >0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls ( t =-3.536, P =0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group ( r =0.494, P <0.01), and the same correlation as CEA and CA(199) group ( r =0.897, P <0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group ( P >0.05), while significant differences were found in CA(125) and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type ( P <0.05). The multiple factors analysis showed that the high level of CA(125) was a independent risk factor of BRCA mutations in sporadic HGSOC ( P =0.007). Conclusion: The combination of CA(125) with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.

Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening.

PubMed

Cohen, Paul A; Flowers, Nicola; Tong, Stephen; Hannan, Natalie; Pertile, Mark D; Hui, Lisa

2016-08-24

Non-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. Pre-symptomatic maternal malignancies have been incidentally detected during NIPT based on abnormal genomic profiles. This low coverage sequencing approach could have potential for ovarian cancer screening in the non-pregnant population. Our objective was to investigate whether plasma DNA sequencing with a clinical whole genome NIPT platform can detect early- and late-stage high-grade serous ovarian carcinomas (HGSOC). This is a case control study of prospectively-collected biobank samples comprising preoperative plasma from 32 women with HGSOC (16 'early cancer' (FIGO I-II) and 16 'advanced cancer' (FIGO III-IV)) and 32 benign controls. Plasma DNA from cases and controls were sequenced using a commercial NIPT platform and chromosome dosage measured. Sequencing data were blindly analyzed with two methods: (1) Subchromosomal changes were called using an open source algorithm WISECONDOR (WIthin-SamplE COpy Number aberration DetectOR). Genomic gains or losses ≥ 15 Mb were prespecified as "screen positive" calls, and mapped to recurrent copy number variations reported in an ovarian cancer genome atlas. (2) Selected whole chromosome gains or losses were reported using the routine NIPT pipeline for fetal aneuploidy. We detected 13/32 cancer cases using the subchromosomal analysis (sensitivity 40.6 %, 95 % CI, 23.7-59.4 %), including 6/16 early and 7/16 advanced HGSOC cases. Two of 32 benign controls had subchromosomal gains ≥ 15 Mb (specificity 93.8 %, 95 % CI, 79.2-99.2 %). Twelve of the 13 true positive cancer cases exhibited specific recurrent changes reported in HGSOC tumors. The NIPT pipeline resulted in one "monosomy 18" call from the cancer group, and two "monosomy X" calls in the controls. Low coverage plasma DNA sequencing used for prenatal testing detected 40.6 % of all HGSOC, including 38 % of early stage cases. Our findings demonstrate the potential of a high throughput sequencing platform to screen for early HGSOC in plasma based on characteristic multiple segmental chromosome gains and losses. The performance of this approach may be further improved by refining bioinformatics algorithms and targeting selected cancer copy number variations.

Evaluation of folate receptor 1 (FOLR1) mRNA expression, its specific promoter methylation and global DNA hypomethylation in type I and type II ovarian cancers.

PubMed

Notaro, Sara; Reimer, Daniel; Fiegl, Heidi; Schmid, Gabriel; Wiedemair, Annamarie; Rössler, Julia; Marth, Christian; Zeimet, Alain Gustave

2016-08-02

In this retrospective study we evaluated the respective correlations and clinical relevance of FOLR1 mRNA expression, FOLR1 promoter specific methylation and global DNA hypomethylation in type I and type II ovarian cancer. Two hundred fifty four ovarian cancers, 13 borderline tumours and 60 samples of healthy fallopian epithelium and normal ovarian epithelium were retrospectively analysed for FOLR1 expression with RT-PCR. FOLR1 DNA promoter methylation and global DNA hypomethylation (measured by means of LINE1 DNA hypomethylation) were evaluated with MethyLight technique. No correlation between FOLR1 mRNA expression and its specific promoter DNA methylation was found neither in type I nor in type II cancers, however, high FOLR1 mRNA expression was found to be correlated with global DNA hypomethylation in type II cancers (p = 0.033). Strong FOLR1 mRNA expression was revealed for Grades 2-3, FIGO stages III-IV, residual disease > 0, and serous histotype. High FOLR1 expression was found to predict increased platinum sensitivity in type I cancers (odds ratio = 3.288; 1.256-10.75; p = 0.020). One-year survival analysis showed in type I cancers an independent better outcome for strong expression of FOLR1 in FIGO stage III and IV. For the entire follow up period no significant independent outcome for FOLR1 expression was revealed. In type I cancers LINE 1 DNA hypomethylation was found to exhibit a worse PFS and OS which were confirmed to be independent in multivariate COX regression model for both PFS (p = 0.026) and OS (p = 0.012). No correlations were found between FOLR1 expression and its specific promoter methylation, however, high FOLR1 mRNA expression was associated with DNA hypomethylation in type II cancers. FOLR1 mRNA expression did not prove to predict clinical outcome in type II cancers, although strong FOLR1 expression generally denotes ovarian cancers with highly aggressive phenotype. In type I cancers, however, strong FOLR1 expression has been found to be a reliable indicator of improved platinum responsiveness reflecting a transient better one-year follow up outcome in highly FOLR1 expressing type I cancers. An independent prognostic role of global DNA hypomethylation was demonstrated in type I tumours.

One-Step Nucleic Acid Amplification (OSNA): A fast molecular test based on CK19 mRNA concentration for assessment of lymph-nodes metastases in early stage endometrial cancer.

PubMed

Fanfani, Francesco; Monterossi, Giorgia; Ghizzoni, Viola; Rossi, Esther D; Dinoi, Giorgia; Inzani, Frediano; Fagotti, Anna; Gueli Alletti, Salvatore; Scarpellini, Francesca; Nero, Camilla; Santoro, Angela; Scambia, Giovanni; Zannoni, Gian F

2018-01-01

The aim of the current study is to evaluate the detection rate of micro- and macro-metastases of the One-Step Nucleic Acid Amplification (OSNA) compared to frozen section examination and subsequent ultra-staging examination in early stage endometrial cancer (EC). From March 2016 to June 2016, data of 40 consecutive FIGO stage I EC patients were prospectively collected in an electronic database. The sentinel lymph node mapping was performed in all patients. All mapped nodes were removed and processed. Sentinel lymph nodes were sectioned and alternate sections were respectively examined by OSNA and by frozen section analysis. After frozen section, the residual tissue from each block was processed with step-level sections (each step at 200 micron) including H&E and IHC slides. Sentinel lymph nodes mapping was successful in 29 patients (72.5%). In the remaining 11 patients (27.5%), a systematic pelvic lymphadenectomy was performed. OSNA assay sensitivity and specificity were 87.5% and 100% respectively. Positive and negative predictive values were 100% and 99% respectively, with a diagnostic accuracy of 99%. As far as frozen section examination and subsequent ultra-staging analysis was concerned, we reported sensitivity and specificity of 50% and 94.4% respectively; positive and negative predictive values were 14.3% and 99%, respectively, with an accuracy of 93.6%. In one patient, despite negative OSNA and frozen section analysis of the sentinel node, a macro-metastasis in 1 non-sentinel node was found. The combination of OSNA procedure with the sentinel lymph node mapping could represent an efficient intra-operative tool for the selection of early-stage EC patients to be submitted to systematic lymphadenectomy.

International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals.

PubMed

Di Renzo, Gian Carlo; Conry, Jeanne A; Blake, Jennifer; DeFrancesco, Mark S; DeNicola, Nathaniel; Martin, James N; McCue, Kelly A; Richmond, David; Shah, Abid; Sutton, Patrice; Woodruff, Tracey J; van der Poel, Sheryl Ziemin; Giudice, Linda C

2015-12-01

Exposure to toxic environmental chemicals during pregnancy and breastfeeding is ubiquitous and is a threat to healthy human reproduction. There are tens of thousands of chemicals in global commerce, and even small exposures to toxic chemicals during pregnancy can trigger adverse health consequences. Exposure to toxic environmental chemicals and related health outcomes are inequitably distributed within and between countries; universally, the consequences of exposure are disproportionately borne by people with low incomes. Discrimination, other social factors, economic factors, and occupation impact risk of exposure and harm. Documented links between prenatal exposure to environmental chemicals and adverse health outcomes span the life course and include impacts on fertility and pregnancy, neurodevelopment, and cancer. The global health and economic burden related to toxic environmental chemicals is in excess of millions of deaths and billions of dollars every year. On the basis of accumulating robust evidence of exposures and adverse health impacts related to toxic environmental chemicals, the International Federation of Gynecology and Obstetrics (FIGO) joins other leading reproductive health professional societies in calling for timely action to prevent harm. FIGO recommends that reproductive and other health professionals advocate for policies to prevent exposure to toxic environmental chemicals, work to ensure a healthy food system for all, make environmental health part of health care, and champion environmental justice. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Novel ways of improving communication with members of health professional associations.

PubMed

Chaudhary, Pushpa; Tuladhar, Heera

2014-10-01

The International Federation of Gynecology and Obstetrics (FIGO) supported the Nepal Society of Obstetricians and Gynaecologists (NESOG) to help influence national health policy and practice through FIGO's Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC) Initiative in Maternal and Newborn Health. An Organizational Capacity Improvement Framework, developed by the Society of Obstetricians and Gynaecologists of Canada (SOGC), was used to evaluate NESOG's initial baseline organizational capacity in 2010. Communication among NESOG members was rated as moderate (39%). Several initiatives, such as the use of high-speed internet access, group SMS texts and emails for information sharing, member profile updates, use of social media, and regular updates to the NESOG website were examples of interventions that resulted in improved participation of members in NESOG's activities. Members were impressively active in reciprocating via Facebook, and via participation in online voting in the NESOG elections (84%). Copyright © 2014. Published by Elsevier Ireland Ltd.

FIGO stage IIIC endometrial cancer identification among patients with complex atypical hyperplasia, grade 1 and 2 endometrioid endometrial cancer: laparoscopic indocyanine green sentinel lymph node mapping versus frozen section of the uterus, why get around the problem?

PubMed

Papadia, Andrea; Gasparri, Maria Luisa; Siegenthaler, Franziska; Imboden, Sara; Mohr, Stefan; Mueller, Michael D

2017-03-01

To compare two surgical strategies used to identify lymph node metastases in patients with preoperative diagnosis of complex atypical hyperplasia (CAH), grade 1 and 2 endometrial cancer (EC). Data on patients with preoperative diagnosis of CAH, grade 1 and 2 EC undergoing laparoscopic indocyanine green (ICG) sentinel lymph node (SLN) mapping followed by frozen section of the uterus were collected. When risk factors were identified at frozen section, patients were subjected to a systematic lymphadenectomy. False negative (FN) rates, negative predictive values (NPV), positive predictive values (PPV) and correlation with stage IIIC EC were calculated for the systematic lymphadenectomy based on frozen section of the uterus and for the SLN mapping. Six (9.5%) out of 63 patients had lymph nodal metastases. Based on frozen section of the uterus, 22 (34.9%) and 15 (22.2%) patients underwent a pelvic and a pelvic and paraaortic lymphadenectomy, respectively. Five patients with stage IIIC disease were identified with a FN rate of 16.7% and a NPV and PPV of 97.6 and 27.3%, respectively. Overall and bilateral detection rates of ICG SLN mapping were 100 and 97.6%, respectively; no FN were recorded. The identification of patients with stage IIIC disease with ICG SLN mapping showed a NPV and PPV of 100%. Correlation between indication to lymphadenectomy and stage IIIC disease was poor (κ = 0.244) when based on frozen section of the uterus and excellent (κ = 1) when based on SLN mapping. ICG SLN mapping reduces the number of unnecessary systematic lymphadenectomies and the risk of underdiagnosing patients with metastatic lymph nodes.

Sentinel Lymph Node (SLN) laparoscopic assessment early stage in endometrial cancer.

PubMed

Gargiulo, T; Giusti, M; Bottero, A; Leo, L; Brokaj, L; Armellino, F; Palladin, L

2003-06-01

The aim of the study was to demonstrate the validity of sentinel lymph node (SLN) detection after injection of radioactive isotope and patent blue dye in patients affected by early stage endometrial cancer. The second purpose was to compare radioactive isotope and patent blue dye migration. Between September 2000 and May 2001, 11 patients with endometrial cancer FIGO stage Ib (n=10) and IIa (n=1) underwent laparoscopic SLN detection during laparoscopic assisted vaginal hysterectomy with bilateral salpingo-oophorectomy and pelvic bilateral systematic lymphadenectomy. Radioactive isotope injection was performed 24 ours before surgery and blue dye injection was performed just before surgery in the cervix at 3, 6, 9 and 12 hours. A 350 mm laparoscopic gamma-scintiprobe MR 100 type 11, (99m)Tc setted (Pol.Hi.Tech.), was used intraoperatively for detecting SLN. Seventeen SLN were detected at lymphoscintigraphy (6 bilateral and 5 monolateral). At laparoscopic surgery the same locations were found belonging at internal iliac lymph nodes (the so called "Leveuf-Godard" area, lateral to the inferior vescical artery, ventral to the origin of uterine artery and medial or caudal to the external iliac vein). Fourteen SLN were negative at histological analysis and only 3 positive for micrometastasis (mean SLN sections = 60. All the other pelvic lymph nodes were negative at histological analysis. The same SLN locations detected with g-scintiprobe were observed during laparoscopy after patent blue dye injection. If the sensitivity of the assessment of SLN is confirmed to be 100%, this laparoscopic approach could change the management of early stage endometrial cancer. The clinical validity of this technique must be evaluated prospectively.

Improved survival of baby boomer women with early-stage uterine cancer: A Surveillance, Epidemiology and End Results (SEER) Study.

PubMed

Elshaikh, Mohamed A; Ruterbusch, Julie; Cote, Michele L; Cattaneo, Richard; Munkarah, Adnan R

2013-11-01

To study the prognostic impact of baby boomer (BB) generation on survival end-points of patients with early-stage endometrial carcinoma (EC). Data were obtained from the SEER registry between 1988-2009. Inclusion criteria included women who underwent hysterectomy for stage I-II EC. Patients were divided into two birth cohorts: BB (women born between 1946 and 1964) and pre-boomers (PB) (born between 1926 and 1945). A total of 30,956 patients were analyzed. Considering that women in the PB group were older than those of the BB generation, the statistical analysis was limited to women 50-59 years of age at the time of diagnosis (n=11,473). Baby boomers had a significantly higher percentage of endometrioid histology (p<0.0001), higher percentage of African American women (p<0.0001), lower tumor grade (p<0.0001), higher number of dissected lymph nodes (LN) (p<0.0001), and less utilization of adjuvant radiation therapy (p=0.0003). Overall survival was improved in women in the BB generation compared to the PB generation (p=0.0003) with a trend for improved uterine cancer-specific survival (p=0.0752). On multivariate analysis, birth cohort (BB vs. PB) was not a significant predictor of survival end-points. Factors predictive of survival included: tumor grade, FIGO stage, African-American race, and increased number of dissected LN. Our study suggests that the survival of BB women between 50-60 years of age is better compared to women in the PB generation. As more BB patients are diagnosed with EC, further research is warranted.

Phase II Trial of Adjuvant Pelvic Radiation “Sandwiched” Between Combination Paclitaxel and Carboplatin in Women with Uterine Papillary Serous Carcinoma

PubMed Central

Einstein, Mark H.; Frimer, Marina; Kuo, Dennis Y-S; Reimers, Laura L.; Mehta, Keyur; Mutyala, Subhakar; Huang, Gloria S.; Hou, June Y.; Goldberg, Gary L.

2013-01-01

Objective To evaluate the safety and survival in women treated with adjuvant pelvic radiation “sandwiched” between six cycles of paclitaxel and carboplatin chemotherapy with completely resected UPSC. Methods Surgically staged women with UPSC (FIGO stage 1-4) and no visible residual disease were enrolled. Treatment involved paclitaxel (175 mg/m2) and carboplatin (AUC=6.0-7.5) every 21 days for 3 doses, followed by radiation therapy (RT), followed by an additional 3 cycles of paclitaxel and carboplatin (AUC=5-6). Survival analysis, using Kaplan-Meier methods, was performed on patients who completed at least 3 cycles of chemotherapy and RT. Results A total of 81 patients were enrolled, of which 72 patients completed the first 3 cycles of chemotherapy followed by prescribed RT. Median age was 67 years (range: 43–82 years). 59/72 (82%) had disease confined to the uterus and 13/72 (18%) had completely resected extra-uterine disease (stage 3&4). 65 (83%) completed the protocol. Overall PFS and OS for combined stage 1&2 patients was 65.5±3.6 months and 76.5±4.3 months, respectively. PFS and OS for combined stage 3&4 patients was 25.8±3.0 and 35.9±5.3 months, respectively. Three-year % survival probability for stage 1&2 patients was 84% and for stage 3&4 patients was 50%. Of the 435 chemotherapy cycles administered, there were 11(2.5%) G3/G4 non-hematologic toxicities. 26(6.0%) cycles had dose reductions and 37(8.5%) had dose delays. Conclusions Compared to prior studies of single modality adjuvant therapy, RT “sandwiched” between paclitaxel and carboplatin chemotherapy is well-tolerated and highly efficacious in women with completely resected UPSC. PMID:22035806

Uterine cervix cancer treatment at Radiumhemmet: 90 years' experience. Time trends of age, stage, and histopathology distribution.

PubMed

Hellman, Kristina; Hellström, Ann-Cathrin; Pettersson, B Folke

2014-04-01

Since the introduction of screening programs for cervical cancer (CC) the incidence has decreased and CC is discovered at an earlier stage. The purpose of this study was to analyze time trends in age, stage, and histopathology over a 90-year period and to our knowledge this is the largest single institutional series in the literature of invasive cervical carcinoma (CC) cases. This is a retrospective study comprising 18,472 women treated for CC from 1914 until 2004 at Radiumhemmet, Stockholm. The material is part of the international CC statistics published since 1937 in the League of Nations' Annual Reports, and since 1958 under the patronage of International Federation of Gynecology and Obstetrics (FIGO). During the 90-year study period, the annual number of cases treated increased to over 400 up until 1965, after which there was a gradual drop to less than 100 cases in 2004. A pronounced shift toward earlier stages at diagnosis was noted. The mean age at diagnosis increased in all stages, predominantly in advanced stages. A reduction in squamous cell carcinoma (SCC) cases and a sixfold increase in the proportion of adenocarcinoma (AC) cases were observed. The mean age at diagnosis for squamous and AC cases shifted after 1970, when the SCC cases ultimately became 3 years older than the AC cases in contrast to around 1950 when they were 3 years younger than the AC cases. The changes in the distribution by age, stage, and histopathology during this 90-year period are probably associated with: improved social conditions and increased access to health care, the introduction of screening programs for CC in the 1960s, and a change in the risk factors for CC (changed sexual behavior, introduction of contraceptive pills, and changed smoking habits). © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence.

PubMed

Kurnit, Katherine C; Kim, Grace N; Fellman, Bryan M; Urbauer, Diana L; Mills, Gordon B; Zhang, Wei; Broaddus, Russell R

2017-07-01

Although the majority of low grade, early stage endometrial cancer patients will have good survival outcomes with surgery alone, those patients who do recur tend to do poorly. Optimal identification of the subset of patients who are at high risk of recurrence and would benefit from adjuvant treatment has been difficult. The purpose of this study was to evaluate the impact of somatic tumor mutation on survival outcomes in this patient population. For this study, low grade was defined as endometrioid FIGO grades 1 or 2, while early stage was defined as endometrioid stages I or II (disease confined to the uterus). Next-generation sequencing was performed using panels comprised of 46-200 genes. Recurrence-free and overall survival was compared across gene mutational status in both univariate and multivariate analyses. In all, 342 patients were identified, 245 of which had endometrioid histology. For grades 1-2, stages I-II endometrioid endometrial cancer patients, age (HR 1.07, 95% CI 1.03-1.10), CTNNB1 mutation (HR 5.97, 95% CI 2.69-13.21), and TP53 mutation (HR 4.07, 95% CI 1.57-10.54) were associated with worse recurrence-free survival on multivariate analysis. When considering endometrioid tumors of all grades and stages, CTNNB1 mutant tumors were associated with significantly higher rates of grades 1-2 disease, lower rates of deep myometrial invasion, and lower rates of lymphatic/vascular space invasion. When both TP53 and CTNNB1 mutations were considered, presence of either TP53 mutation or CTNNB1 mutation remained a statistically significant predictor of recurrence-free survival on multivariate analysis and was associated with a more precise confidence interval (HR 4.69, 95% CI 2.38-9.24). Thus, mutational analysis of a 2 gene panel of CTNNB1 and TP53 can help to identify a subset of low grade, early stage endometrial cancer patients who are at high risk of recurrence.

Functional Assessment of Synoptic Pathology Reporting for Ovarian Cancer.

PubMed

Słodkowska, Janina; Cierniak, Szczepan; Patera, Janusz; Kopik, Jarosław; Baranowski, Włodzimierz; Markiewicz, Tomasz; Murawski, Piotr; Buda, Irmina; Kozłowski, Wojciech

2016-01-01

Ovarian cancer has one of the highest death/incidence rates and is commonly diagnosed at an advanced stage. In the recent WHO classification, new histotypes were classified which respond differently to chemotherapy. The e-standardized synoptic cancer pathology reports offer the clinicians essential and reliable information. The aim of our project was to develop an e-template for the standardized synoptic pathology reporting of ovarian carcinoma [based on the checklist of the College of American Pathologists (CAP) and the recent WHO/FIGO classification] to introduce a uniform and improved quality of cancer pathology reports. A functional and qualitative evaluation of the synoptic reporting was performed. An indispensable module for e-synoptic reporting was developed and integrated into the Hospital Information System (HIS). The electronic pathology system used a standardized structure with drop-down lists of defined elements to ensure completeness and consistency of reporting practices with the required guidelines. All ovarian cancer pathology reports (partial and final) with the corresponding glass slides selected from a 1-year current workflow were revised for the standard structured reports, and 42 tumors [13 borderline tumors and 29 carcinomas (mainly serous)] were included in the study. Analysis of the reports for completeness against the CAP checklist standard showed a lack of pTNM staging in 80% of the partial or final unstructured reports; ICD-O coding was missing in 83%. Much less frequently missed or unstated data were: ovarian capsule infiltration, angioinvasion and implant evaluation. The e-records of ovarian tumors were supplemented with digital macro- and micro-images and whole-slide images. The e-module developed for synoptic ovarian cancer pathology reporting was easily incorporated into HIS.CGM CliniNet and facilitated comprehensive reporting; it also provided open access to the database for concerned recipients. The e-synoptic pathology reports appeared more accurate, clear and conclusive than traditional narrative reports. Standardizing structured reporting and electronic tools allows open access and downstream utilization of pathology data for clinicians and tumor registries. © 2016 S. Karger AG, Basel.

Primary Fallopian Tube Carcinoma: A Case Report and Literature Review

PubMed Central

Rexhepi, Meral; Trajkovska, Elizabeta; Ismaili, Hysni; Besimi, Florin; Rufati, Nagip

2017-01-01

BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare tumour of the female genital tract with an incidence of 0.1-1.8% of all genital malignancies, and it is very difficult to diagnose preoperatively, because of its non-specific symptomatology. In most cases, it is an intraoperative finding or a histopathological diagnosis. It is a tumour that histologically and clinically resembles epithelial ovarian cancer. CASE PRESENTATION: We are reporting a case of a 62-year-old, postmenopausal women with primary fallopian tube carcinoma of the right fallopian tube in stage IA. The patient has lower abdominal pain, watery vaginal discharge and repeated episodes of bleeding from the vagina. The clinical and radiological findings suggested a right adnexal tumour with elevated CA-125 levels. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and peritoneal washing were performed. Pathologic confirmation of primary serous cystadenocarcinoma of the right fallopian tube was made. Peritoneal washings were negative for malignancy. FIGO stage was considered as IA, and the patient received no courses of chemotherapy and postoperative radiation because she refused it. Ten months after initial surgery, the patient is alive and in good condition. CONCLUSION: Cytoreduction surgery followed by adequate cycles of chemotherapy is an important strategy to improve patients’ prognosis. PMID:28698755

[Adenocarcinoma of the uterine cervix: particularities in diagnosis and treatment].

PubMed

Vandenbroucke, L; Robert, A-L; Lavoué, V; Foucher, F; Henno, S; Levêque, J

2013-05-01

The adenocarcinoma of the uterine cervix accounts for 10 to 20% of the premalignant and malignant lesions and is different from the cervical intraepithelial neoplasia and invasive squamous cell carcinoma. Recent literature review (from 1985 to 2012) based on the literature available. Adenocarcinoma in situ is an induced HPV lesion (role of HPV 18) of the glandular epithelium: its preferential endocervical situation explains the difficulties in the diagnosis and follow-up after conservative treatment. If the hysterectomy remains the gold standard for treatment, the conservative treatments (resection in sano of the lesions with margins of more than 1cm, meticulous study of the operative specimen, compliance with the follow-up) are possible in the young patients who desire to preserve their fertility. The invasive adenocarcinoma is characterized by a more difficult diagnosis because of its endocervical development, and a prognosis less favorable when compared to squamous cell carcinoma with a greater frequency of the lymphatic node involvement and metastatic diffusion. Its treatment must take into account the particular gravity of the factors of worse prognosis (FIGO stage, tumor size, lymphatic node spreading, adenosquamous histological subtype) in particular in the advanced stages and includes beside the surgery, radiotherapy and chemotherapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Sentinel lymph node detection in patients with early cervical cancer.

PubMed

Acharya, B C; Jihong, L

2009-01-01

Lymph node status is the most important independent prognostic factor in early stage cervical cancer. Intraoperative lymphatic mapping and sentinel lymph node detection have been increasingly evaluated in the treatment of a variety of solid tumors, particularly breast cancer and cutaneous melanoma. This study evaluated the feasibility of these procedures in patients undergoing radical hysterectomy with pelvic lymphadenectomy for early cervical cancer. A total of 30 patients with histologically diagnosed FIGO stage IA to IIA cervical cancer were enrolled to this study. They were scheduled to undergo radical abdominal hysterectomy and pelvic lymphadenectomy after injecting patent blue dye in cervix. A total of 60 SLNs (mean 2.5) were detected in 24 patients with detection rate of 80%. Bilateral SLNs were detected in 70.1% of cases. SLNs were identified in obturator and external iliac areas in 50% and 31.7%, respectively; no SLNs were discovered in the common iliac region. Seven patients (23.3%) had lymph node metastases; one of these had false negative SLN.The false negative rate and negative predictive value were 14.3% and 94.4%, respectively. SLN detection procedure with blue dye technique is a feasible procedure in cervical cancer. Patent blue dye is cheap, safe and effective tracer to detect sentinel node in carcinoma of cervix.

LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk Endometrial Cancer.

PubMed

Noci, Ivo; Sorbi, Flavia; Mannini, Luca; Projetto, Elisabetta; Pillozzi, Serena; Ghizzoni, Viola; Lottini, Tiziano; Moncini, Daniela; Baroni, Gianna; Mungai, Francesco; Arcangeli, Annarosa; Fambrini, Massimiliano

2016-01-01

A 51 year-old woman was diagnosed with endometrial cancer (EC) and underwent surgical staging. Pathological evaluation showed a 2 cm × 1 cm G2 endometrioid EC with a 30% myometrial deep invasion (FIGO Stage 1A). The patient was classified as low risk of recurrence, and no adjuvant treatment was offered. Six months after surgery, the patient developed an early vescico-vaginal recurrence, and chemotherapy treatment was started. Few months later, a subsequent involvement of vaginal wall, ileum, and omentum was detected, and the patient underwent second surgery. LH/hCG-receptor (LH/hCG-R) expression has been previously reported to be associated with an invasive phenotype in EC cells. Moreover, in a preclinical mouse model of EC behaves as a prometastatic molecular device. We analyzed the expression level of LH/hCG-R in cancer specimens collected during surgeries. Molecular and immunohistochemical analyses showed a strong expression of both mRNA and protein for LH/hCG-R in all specimens. LH/hCG-R expression may be assessed together with other clinicopathological parameters in order to better predict the risk of recurrence in low-risk EC patients. Further clinical trials are warranted in order to validate LH/hCG-R as biomarker in EC.

Should helical tomotherapy replace brachytherapy for cervical cancer? Case report.

PubMed

Hsieh, Chen-Hsi; Wei, Ming-Chow; Hsu, Yao-Peng; Chong, Ngot-Swan; Chen, Yu-Jen; Hsiao, Sheng-Mou; Hsieh, Yen-Ping; Wang, Li-Ying; Shueng, Pei-Wei

2010-11-23

Stereotactic body radiation therapy (SBRT) administered via a helical tomotherapy (HT) system is an effective modality for treating lung cancer and metastatic liver tumors. Whether SBRT delivered via HT is a feasible alternative to brachytherapy in treatment of locally advanced cervical cancer in patients with unusual anatomic configurations of the uterus has never been studied. A 46-year-old woman presented with an 8-month history of abnormal vaginal bleeding. Biopsy revealed squamous cell carcinoma of the cervix. Magnetic resonance imaging (MRI) showed a cervical tumor with direct invasion of the right parametrium, bilateral hydronephrosis, and multiple uterine myomas. International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical cancer was diagnosed. Concurrent chemoradiation therapy (CCRT) followed by SBRT delivered via HT was administered instead of brachytherapy because of the presence of multiple uterine myomas with bleeding tendency. Total abdominal hysterectomy was performed after 6 weeks of treatment because of the presence of multiple uterine myomas. Neither pelvic MRI nor results of histopathologic examination at X-month follow-up showed evidence of tumor recurrence. Only grade 1 nausea and vomiting during treatment were noted. Lower gastrointestinal bleeding was noted at 14-month follow-up. No fistula formation and no evidence of haematological, gastrointestinal or genitourinary toxicities were noted on the most recent follow-up. CCRT followed by SBRT appears to be an effective and safe modality for treatment of cervical cancer. Larger-scale studies are warranted.

High-dose rate brachytherapy in the treatment of carcinoma of uterine cervix: twenty-year experience with cobalt after-loading system.

PubMed

Mosalaei, A; Mohammadianpanah, M; Omidvari, S; Ahmadloo, N

2006-01-01

This retrospective analysis aims to report results of patients with cancer of uterine cervix treated with external-beam radiotherapy (EBR) and high-dose rate (HDR) brachytherapy, using manual treatment planning. From 1975 to 1995, 237 patients with FIGO stages IIB-IVA and mean age of 54.31 years were treated. EBR dose to the whole pelvis was 50 Gy in 25 fractions. Brachytherapy with HDR after-loading cobalt source (Cathetron) was performed following EBR completion with a dose of 30 Gy in three weekly fractions of 10 Gy to point A. Survival, local control, and genitourinary and gastrointestinal complications were assessed. In a median follow-up of 60.2 months, the 10-year overall and disease-free survival rate was 62.4%. Local recurrence was seen in 12.2% of patients. Distant metastases to the lymph nodes, peritoneum, lung, liver, and bone occurred in 25.3% of patients. Less than 6% of patients experienced severe genitourinary and/or gastrointestinal toxicity that were relieved by surgical intervention. No treatment-related mortality was seen. This series suggests that 50 Gy to the whole pelvis together with three fractions of 10 Gy to point A with HDR brachytherapy is an effective fractionation schedule in the treatment of locally advanced cancer of cervix. To decrease the complications, newer devices and treatment planning may be beneficial.

Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer.

PubMed

Tangjitgamol, Siriwan; Katanyoo, Kanyarat; Laopaiboon, Malinee; Lumbiganon, Pisake; Manusirivithaya, Sumonmal; Supawattanabodee, Busaba

2014-12-03

Current standard treatment for patients with cervical cancer who have locally advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IVA) is concurrent chemoradiation therapy (CCRT). However, less than two-thirds of patients in this group survive for longer than five years post treatment. Adjuvant chemotherapy (ACT) can be given in an attempt to improve survival by eradicating residual disease in the pelvis and treating occult disease outside the pelvic radiation field. However, inconsistency in trial design, inclusion criteria for participants, interventions and survival benefit has been noted among trials of ACT after CCRT for locally advanced cervical cancer (LACC). To evaluate the effect of adjuvant chemotherapy (ACT) after concurrent chemoradiation (CCRT) on survival of women with locally advanced cervical cancer compared with CCRT alone. We searched the Cochrane Gynaecological Review Group Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and conference proceedings to March 2014. We handsearched citation lists of relevant studies. Randomised controlled trials (RCTs) comparing CCRT alone versus CCRT plus ACT were included. Patients were diagnosed with cervical cancer FIGO stage IIB to IVA with a histopathology of squamous cell carcinoma, adenosquamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma. Two review authors (ST, KK) selected relevant trials, extracted data, assessed risk of bias independently, compared results and resolved disagreements by discussion. We identified two RCTs involving 978 women with cervical cancer stage IIB to IVA. As the trials were significantly different clinically, we did not perform meta-analyses. One industry-funded trial involving 515 women compared CCRT (cisplatin) versus CCRT (cisplatin and gemcitabine) plus ACT (two additional cycles). This trial reported significant improvement in progression-free survival (PFS) and overall survival (OS) in women who were given CCRT plus ACT compared with those treated with CCRT alone: Three-year PFS was 74.4% versus 65.0% (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.49 to 0.95, P value 0.027), and three-year OS was 80% versus 69% (HR 0.68, 95% CI 0.49 to 0.95, P value 0.022). However, as the CCRT chemotherapy differed between the two arms, we considered the findings to be at high risk of bias.The second trial was a four-arm study from which we extracted data on 463 women in two study arms receiving CCRT (intravenous mitomycin C and oral 5-fluorouracil (5-FU)) or CCRT plus ACT (oral 5-FU for three cycles). The HR for OS in women who received ACT after CCRT compared with the HR for OS in those who were given CCRT alone was 1.309 (95% CI 0.795 to 2.157), and the HR for disease-free survival (DFS) was 1.125 (95% CI 0.799 to 1.586).Haematological adverse events were more common in the ACT arms of both trials. Quality of life (QoL) was not reported in either trial. With limited data from only two trials, we found insufficient evidence to support the use of ACT after CCRT. Future large trials are required to demonstrate efficacy, toxicities and QoL.

Laparoscopic hysterectomy with or without pelvic lymphadenectomy or sampling in a high-risk series of patients with endometrial cancer

PubMed Central

Willis, Susan F; Barton, Desmond; Ind, Thomas EJ

2006-01-01

Background The purpose of the study was to determine the outcome of all patients with endometrial adenocarcinoma cancer treated by laparoscopic hysterectomy at our institution, many of whom were high-risk for surgery. Methods Data was collected by a retrospective search of the case notes and Electronic Patient Records of the thirty eight patients who underwent laparoscopic hysterectomy for endometrial cancer at our institutions. Results The median body mass index was 30 (range 19–67). Comorbidities were present in 76% (29 patients); 40% (15 patients) had a single comorbid condition, whilst 18% (7 patients) had two, and a further 18% (7 patients) had more than two. Lymphadenectomy was performed in 45% (17 patients), and lymph node sampling in 21% (8 patients). Median operating time was 210 minutes (range 70–360 minutes). Median estimated blood loss was 200 ml (range 50–1000 ml). There were no intraoperative complications. Post-operative complications were seen in 21% (2 major, 6 minor). Blood transfusion was required in 5% (2 patients). The median stay was 4 post-operative nights (range 1–25 nights). In those patients undergoing lymphadenectomy, the mean number of nodes taken was fifteen (range 8–26 nodes). The pathological staging was FIGO stage I 76% (29 patients), stage II 8% (3 patients), stage III 16% (6 patients). The pathological grade was G1 31% (16 patients), G2 45% (17 patients), G3 24% (8 patients). Conclusion Laparoscopic hysterectomy can be safely carried out in patients at high risk for surgery, with no compromise in terms of outcomes, whilst providing all the benefits inherent in minimal access surgery. PMID:16968556

Abnormal uterine bleeding unrelated to structural uterine abnormalities: management in the perimenopausal period.

PubMed

Sabbioni, Lorenzo; Zanetti, Isabella; Orlandini, Cinzia; Petraglia, Felice; Luisi, Stefano

2017-02-01

Abnormal uterine bleeding (AUB) is one of the commonest health problems encountered by women and a frequent phenomenon during menopausal transition. The clinical management of AUB must follow a standardized classification system to obtain the better diagnostic pathway and the optimal therapy. The PALM-COEIN classification system has been approved by the International Federation of Gynecology and Obstetrics (FIGO); it recognizes structural causes of AUB, which can be measured visually with imaging techniques or histopathology, and non-structural entities such as coagulopathies, ovulatory dysfunctions, endometrial and iatrogenic causes and disorders not yet classified. In this review we aim to evaluate the management of nonstructural causes of AUB during the menopausal transition, when commonly women experience changes in menstrual bleeding patterns and unexpected bleedings which affect their quality of life.

Application of carbon nanoparticles in laparoscopic sentinel lymph node detection in patients with early-stage cervical cancer.

PubMed

Lu, Yan; Wei, Jin-Ying; Yao, De-Sheng; Pan, Zhong-Mian; Yao, Yao

2017-01-01

To investigate the value of carbon nanoparticles in identifying sentinel lymph nodes in early-stage cervical cancer. From January 2014 to January 2016, 40 patients with cervical cancer stage IA2-IIA, based on the International Federation of Gynecology and Obstetrics (FIGO) 2009 criteria, were included in this study. The normal cervix around the tumor was injected with a total of 1 mL of carbon nanoparticles (CNP)at 3 and 9 o'clock. All patients then underwent laparoscopic pelvic lymph node dissection and radical hysterectomy. The black-dyed sentinel lymph nodes were removed for routine pathological examination and immunohistochemical staining. Among the 40 patients, 38 patients had at least one sentinel lymph node (SLN). The detection rate was 95% (38/40). One hundred seventy-three SLNs were detected with an average of 3.9 SLNs per side. 25 positive lymph nodes, which included 21 positive SLNs, were detected in 8 (20%) patients. Sentinel lymph nodes were localized in the obturator (47.97%), internal lilac (13.87%), external lilac (26.59%), parametrial (1.16%), and common iliac (8.67%) regions. The sensitivity of the SLN detection was 100% (5/5), the accuracy was 97.37% (37/38), and the negative predictive value was 100. 0% and the false negative rate was 0%. Sentinel lymph nodes can be used to accurately predict the pathological state of pelvic lymph nodes in early cervical cancer. The detection rates and accuracy of sentinel lymph node were high. Carbon nanoparticles can be used to trace the sentinel lymph node in early cervical cancer.

Intraoperative sentinel node identification in early stage cervical cancer using a combination of radiolabeled albumin injection and isosulfan blue dye injection.

PubMed

Martínez-Palones, José M; Gil-Moreno, Antonio; Pérez-Benavente, María A; Roca, Isabel; Xercavins, Jordi

2004-03-01

We investigated the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m-labeled human serum albumin and isosulfan blue dye injection in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. Between September 2000 and October 2002, 25 patients with cervical cancer FIGO stage I (n=24) or stage II (n=1) underwent sentinel lymph node detection with preoperative lymphoscintigraphy (technetium-99m colloid albumin injection around the tumor) and intraoperative lymphatic mapping with blue dye and a handheld or laparoscopic gamma probe. Complete pelvic or paraaortic lymphadenectomy was performed in all cases by open surgery or laparoscopic surgery. In 23 evaluable patients, a total of 51 sentinel lymph nodes were detected by lymphoscintigraphy (mean 2.21 nodes per patient). Intraoperatively, 61 sentinel lymph nodes were identified, with a mean of 2.52 nodes per patient by gamma probe and a mean of 1.94 nodes per patient after isosulfan blue injection. Forty percent of sentinel nodes were found in the interiliac region and 25% in the external iliac area. Microscopic nodal metastases (four nodes) were confirmed in 12% of cases. All these lymph nodes were previously detected as sentinel lymph nodes. The remaining 419 nodes after pelvic lymphadenectomy were histologically negative. Sentinel lymph node identification with technetium-99m-labeled nanocolloid combined with blue dye injection is feasible and showed a 100% negative predictive value, and potentially identified women in whom lymph node dissection can be avoided.

Clinicopathological significance and prognostic value of myoinvasive patterns in endometrial endometrioid carcinoma.

PubMed

Amălinei, Cornelia; Aignătoaei, Anda Maria; Balan, Raluca Anca; Giuşcă, Simona Eliza; Lozneanu, Ludmila; Avădănei, Elena Roxana; Căruntu, Irina Draga

2018-01-01

Endometrioid endometrial carcinoma has an overall good prognosis. However, variable five-year survival rates (92%-42%) have been reported in FIGO stage I, suggesting the involvement of other factors related to tumor biological behavior. These may be related to the role played by epithelial-mesenchymal transition (EMT) and cancer stem cells in endometrial carcinogenesis. In this context, our review highlights the prognostic significance of several types of myoinvasion in low grade, low stage endometrioid endometrial carcinoma, as a reflection of these molecular changes at the invasive front. According to recently introduced myoinvasive patterns, the diffusely infiltrating and microcystic, elongated, and fragmented (MELF) patterns show loss of hormone receptors, along with EMT and high expression of cancer stem cell markers, being associated with a poor prognosis. Additionally, MELF pattern exhibits a high incidence of lymphovascular invasion and lymph node metastases. Conversely, the broad front pattern has a good prognosis and a low expression of EMT and stem cells markers. Similarly, the adenomyosis (AM)-like and adenoma malignum patterns of invasion are associated to a favorable prognosis, but nevertheless, they raise diagnostic challenges. AM-like pattern must be differentiated from carcinoma invasion of AM foci, while adenoma malignum pattern creates difficulties in appreciating the depth of myoinvasion and requires differential diagnosis with other conditions. Another pattern expecting its validation and prognostic significance value is the nodular fasciitis-like stroma and large cystic growth pattern. In practice, the knowledge of these patterns of myoinvasion may be valuable for the correct assessment of stage, may improve prognosis evaluation and may help identify molecules for future targeted therapies.

PALM-COEIN Nomenclature for Abnormal Uterine Bleeding.

PubMed

Deneris, Angela

2016-05-01

Approximately 30% of women will experience abnormal uterine bleeding (AUB) during their life time. Previous terms defining AUB have been confusing and imprecisely applied. As a consequence, both clinical management and research on this common problem have been negatively impacted. In 2011, the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Group (FMDG) published PALM-COEIN, a new classification system for abnormal bleeding in the reproductive years. Terms such as menorrhagia, menometrorrhagia, metrorrhagia, dysfunctional uterine bleeding, polymenorrhea, oligomenorrhea, and uterine hemorrhage are no longer recommended. The PALM-COEIN system was developed to standardize nomenclature to describe the etiology and severity of AUB. A brief description of the PALM-COEIN nomenclature is presented as well as treatment options for each etiology. Clinicians will frequently encounter women with AUB and should report findings utilizing the PALM-COEIN system. © 2016 by the American College of Nurse-Midwives.

[Grading of gynecological tumors : Current aspects].

PubMed

Horn, L-C; Mayr, D; Brambs, C E; Einenkel, J; Sändig, I; Schierle, K

2016-07-01

Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3‑tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract.

CHEMOTHERAPY INTENSITY AND TOXICITY AMONG BLACK AND WHITE WOMEN WITH ADVANCED AND RECURRENT ENDOMETRIAL CANCER: A GYNECOLOGIC ONCOLOGY GROUP STUDY

PubMed Central

Farley, John H.; Tian, Chunqiao; Rose, G. Scott; Brown, Carol L.; Birrer, Michael; Risinger, John I; Thigpen, J. Tate; Fleming, Gini F.; Gallion, Holly H.; Maxwell, G. Larry

2009-01-01

OBJECTIVE: The purpose of this study was to confirm whether Black and White women with endometrial cancer are equally tolerant of chemotherapy and identify factors that impact survival. METHODS: A retrospective review of 169 Black women and 982 White women with FIGO Stage III/IV or recurrent endometrial carcinoma was performed. All patients received doxorubicin combined with cisplatin. Chemotherapy parameters that were reviewed included relative dose (RD), relative time (RT), and relative dose intensity (RDI). Treatment cycles ≥ 7 were defined as treatment completion. RESULTS: Although Black patients were more likely to experience grade 3-4 anemia (20% vs. 14%) and genitourinary (5% vs. 1%) toxicity, and less likely to experience severe GI toxicity (10% vs. 17%), the overall incidence of grade 3-4 treatment-related chemotoxicity was the same between the two groups (82% vs. 82%). There were no differences in the number of cycles received, RD (0.57 vs. 0.58), RT (0.77 vs. 0.78), or RDI (0.76 vs. 0.76) for Black and White patients. CONCLUSION: Black patients with advanced stage or recurrent endometrial cancer, treated on four GOG protocols, had similar dose intensity and severe chemotherapy-related toxicity compared to White patients, suggesting that previously described racial disparities in survival among patients in GOG trials may have an novel etiology. PMID:19924790

Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma.

PubMed

Kübler, Kirsten; Ayub, Tiyasha H; Weber, Sarah K; Zivanovic, Oliver; Abramian, Alina; Keyver-Paik, Mignon-Denise; Mallmann, Michael R; Kaiser, Christina; Serçe, Nuran Bektas; Kuhn, Walther; Rudlowski, Christian

2014-11-01

Endometrial adenocarcinoma is one of the most common gynecologic malignancies worldwide and in stages confined to the uterus considered to have an excellent prognosis. However, in advanced or recurrent cases when surgery fails to achieve disease control other treatment options are less effective. Thus, new therapeutic avenues are needed. To provide the rationale for the use of novel agents that target immune checkpoints 163 type I endometrial cancer samples were immunohistochemically screened for the presence of CD163(+) tumor-associated macrophages and Foxp3(+) regulatory T cells. Further, a D2-40-based evaluation of lymph vessel density and lymphovascular space invasion was carried out. Correlation analysis with clinicopathological parameters was performed; Kaplan-Meier curves were generated; multivariate analysis was undertaken as appropriate. A substantial amount of tumor-associated macrophages and regulatory T cells was detected in all specimens characterizing endometrial cancer as an immunogenic tumor. However, only the increased infiltration of tumor-associated macrophages was proportionally associated with advanced FIGO stages, high tumor grade, increased lymph vessel density, lymphovascular space invasion and lymph node metastasis. Thus, the presence of tumor-associated macrophages indicates aggressive tumor behavior and appeared to be an independent prognostic factor for recurrence-free survival. Our results make future therapeutic approaches that target tumor-associated macrophages reasonable to improve the outcome of women with advanced or recurrent endometrial adenocarcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Increasing access to legal termination of pregnancy and postabortion contraception at the University Teaching Hospital, Lusaka, Zambia.

PubMed

Macha, Swebby; Muyuni, Mutinta; Nkonde, Scholastica; Faúndes, Anibal

2014-07-01

The Zambian Association of Gynecology and Obstetrics is one of the International Federation of Gynecology and Obstetrics (FIGO) member societies participating in the FIGO Initiative for the Prevention of Unsafe Abortion and its Consequences from the East, Central, and Southern Africa region. The activities included in this country's plan of action were to provide access to safe abortion within the full extent of the law to women receiving care at the University Teaching Hospital in Lusaka, and to increase the proportion of women leaving the hospital with a contraceptive method. Zambian law regarding abortion is liberal, but in general it was not applied until very recently. The proportion of legal terminations of pregnancy among patients receiving abortion care at the hospital increased from 3.2% in 2009 to 7.7% in 2011, while the percentage of women leaving the hospital with a contraceptive method increased from 25.3% to 69.4% over the same period. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Automatic evaluation of intrapartum fetal heart rate recordings: a comprehensive analysis of useful features.

PubMed

Chudáček, V; Spilka, J; Janků, P; Koucký, M; Lhotská, L; Huptych, M

2011-08-01

Cardiotocography is the monitoring of fetal heart rate (FHR) and uterine contractions (TOCO), used routinely since the 1960s by obstetricians to detect fetal hypoxia. The evaluation of the FHR in clinical settings is based on an evaluation of macroscopic morphological features and so far has managed to avoid adopting any achievements from the HRV research field. In this work, most of the features utilized for FHR characterization, including FIGO, HRV, nonlinear, wavelet, and time and frequency domain features, are investigated and assessed based on their statistical significance in the task of distinguishing the FHR into three FIGO classes. We assess the features on a large data set (552 records) and unlike in other published papers we use three-class expert evaluation of the records instead of the pH values. We conclude the paper by presenting the best uncorrelated features and their individual rank of importance according to the meta-analysis of three different ranking methods. The number of accelerations and decelerations, interval index, as well as Lempel-Ziv complexity and Higuchi's fractal dimension are among the top five features.

Assessment of features for automatic CTG analysis based on expert annotation.

PubMed

Chudácek, Vacláv; Spilka, Jirí; Lhotská, Lenka; Janku, Petr; Koucký, Michal; Huptych, Michal; Bursa, Miroslav

2011-01-01

Cardiotocography (CTG) is the monitoring of fetal heart rate (FHR) and uterine contractions (TOCO) since 1960's used routinely by obstetricians to detect fetal hypoxia. The evaluation of the FHR in clinical settings is based on an evaluation of macroscopic morphological features and so far has managed to avoid adopting any achievements from the HRV research field. In this work, most of the ever-used features utilized for FHR characterization, including FIGO, HRV, nonlinear, wavelet, and time and frequency domain features, are investigated and the features are assessed based on their statistical significance in the task of distinguishing the FHR into three FIGO classes. Annotation derived from the panel of experts instead of the commonly utilized pH values was used for evaluation of the features on a large data set (552 records). We conclude the paper by presenting the best uncorrelated features and their individual rank of importance according to the meta-analysis of three different ranking methods. Number of acceleration and deceleration, interval index, as well as Lempel-Ziv complexity and Higuchi's fractal dimension are among the top five features.

How the ovules get enclosed in magnoliaceous carpels.

PubMed

Zhang, Xin; Liu, Wenzhe; Wang, Xin

2017-01-01

Angiosperms distinguish themselves from gymnosperms by their ovules that are enclosed before pollination. However, how the ovules get enclosed in angiosperms remains a mystery, especially for Magnoliaceae. The only key to this mystery is finding a series of carpels transitional from fully closed with enclosed ovules to open with naked ovules. We use routine paraffin section technology, LM, SEM to document the morphology and anatomy of carpel variation in Michelia figo (Magnoliaceae). A series of carpel variations within a single flower of Michelia figo (Magnoliaceae) are documented, in which the ovules are exposed in atypical carpels. These atypical and typical carpels for the first time demonstrate clearly how the naked ovule get enclosed. Each atypical carpel, with naked ovules, clearly comprises two parts, namely, subtending foliar part and branches bearing ovules, suggesting that a typical carpel is actually an end-product of the fusion between the ovuliferous branches and subtending foliar parts. The only difference among these carpels is the extent of fusion between these two parts. This generalization is in full agreement with the molecular genetic studies on angiosperm flowers.

Use of the sentinel node procedure to stage endometrial cancer.

PubMed

Ballester, Marcos; Dubernard, Gil; Rouzier, Roman; Barranger, Emmanuel; Darai, Emile

2008-05-01

Lymph node status is a major prognostic factor and a criterion for adjuvant therapy in endometrial cancer. The sentinel lymph node (SN) procedure has emerged as a possible alternative to systematic lymphadenectomy. The aims of this study were to determine the detection rate and the false-negative rate of the SN procedure, and its contribution to the staging of women with endometrial cancer. Forty-six patients with endometrial cancer underwent the sentinel node procedure followed by pelvic lymphadenectomy. SNs were detected with a dual or single labelling method in 39 and 7 cases, respectively. All SNs were analysed by both hematoxylin and eosin (H&E) staining and immunochemistry. SNs were identified in 40 patients (87%), whose mean number of SN was 2.6 (range 1-5). The SN detection rate was significantly lower with the single label than with the dual label (p = 0.01). Ten women (25%) had a positive SN on final histology (i.e. there were no false negatives). A correlation was observed between lymph node involvement and both histological grade (p = 0.01) and lymphovascular space involvement (p = 0.001). The stage predicted by magnetic resonance (MR) imaging correlated poorly with the Federation International of Gynaecology and Obstetrics (FIGO) stage. Among the ten women with a positive SN, three of the four women with a grade 1 tumour at biopsy had grade 2-3 disease on final histology. Seven of the ten women with a positive SN underwent external pelvic radiotherapy, based solely on their SN involvement. The SN procedure can reliably determine lymph node status in women with endometrial cancer. Given the limited capacity of MR imaging to detect myometrial invasion, and of biopsy to determine histological grade, our results support the systematic use of the SN procedure in women with endometrial cancer, including those with presumed early-stage disease and/or well-differentiated tumours.

Risk of port-site metastases in pelvic cancers after robotic surgery.

PubMed

Seror, J; Bats, A-S; Bensaïd, C; Douay-Hauser, N; Ngo, C; Lécuru, F

2015-04-01

To assess the risk of occurrence of port-site metastases after robotic surgery for pelvic cancer. Retrospective study from June 2007 to March 2013 of patients with gynecologic cancer who underwent robot-assisted surgery. We collected preoperative data, including characteristics of patients and FIGO stage, intraoperative data (surgery performed, number of ports), and postoperative data (occurrence of metastases, occurrence of port-site metastases). 115 patients were included in the study: 61 with endometrial cancer, 50 with cervical cancer and 4 with ovarian cancer. The surgical procedures performed were: hysterectomy with bilateral salpingo-oophorectomy, radical hysterectomy, pelvic lymphadenectomy, para-aortic lymphadenectomy and omentectomy. All surgical procedures required the introduction of 4 ports, 3 for the robot and 1 for the assistant. With a mean follow-up of 504.4 days (507.7 days for endometrial cancer, 479.5 days for cervical cancer, and 511.3 for ovarian cancer), we observed 9 recurrences but no port-site metastasis. No port-site metastasis has occurred in our series. However, larger, prospective and randomized works are needed to formally conclude. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery.

PubMed

Mabuchi, Yasushi; Yahata, Tamaki; Kobayashi, Aya; Tanizaki, Yuko; Minami, Sawako; Ino, Kazuhiko

2015-06-01

Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

IMP3 Expression in Borderline Tumors of the Ovary.

PubMed

El-Balat, Ahmed; Sänger, Nicole; Karn, Thomas; Becker, Sven; Holtrich, Uwe; Muallem, Zelal; Arsenic, Ruza

2017-02-01

Borderline ovarian tumors (BOTs) have a less aggressive behavior than invasive epithelial ovarian tumors. Still some patients relapse or succumb to disease. Molecular markers that reliably predict prognosis are lacking. Insulin-like growth factor II mRNA-binding protein (IMP3) has been suggested as a prognostic marker in colorectal, hepatocellular, and ovarian clear-cell carcinomas. We analyzed the expression of IMP3 by immunohistochemistry in a cohort of 140 BOT and its association with histopathological features. We found no association of IMP3 expression with patients' age, FIGO stage, microinvasion, and presence of implants. In contrast, IMP3 expression correlated to mucinous subtype of BOTs (42.2% vs. 9.5% among other subtypes) (p<0.001). IMP3 expression was found to be associated with the presence of in situ carcinoma in MBOT, but not in other subtypes (p=0.021). Expression of IMP3 in BOT is associated with the mucinous subtype and may serve as an early indicator for the development of malignant features. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Inelastic Deformation of Metals and Structures under Dynamic and Quasi-Static Cyclic Loading.

DTIC Science & Technology

1983-05-01

the above inequa - lities is denoted by *. Note that ratchetting limits p corresponding to perfect plasticity material (Figo4b) can be generated from the...due to the employment of the kinematic hardening rule. In the intermediate regime R1 +R2, the behaviour changes from R1 to R2 when sufficient hardening

Intravaginal brachytherapy alone for intermediate-risk endometrial cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alektiar, Kaled M.; Venkatraman, Ennapadam; Chi, Dennis S.

2005-05-01

Purpose: Despite the results of the Gynecologic Oncology Group trial No. 99 (GOG no. 99), some unanswered questions still remain about the role of adjuvant radiotherapy (RT) for intermediate-risk endometrial cancer. First, can intravaginal brachytherapy (IVRT) alone substitute for external beam RT but without added morbidity? Second, is the high-risk (HR) definition from GOG no. 99 a useful tool to predict pelvic recurrence specifically? The purpose of this study was to try to answer these questions in a group of patients with Stage IB-IIB endometrial carcinoma treated with high-dose-rate (HDR) IVRT alone. Methods and Materials: Between November 1987 and Decembermore » 2002, 382 patients with Stage IB-IIB endometrial carcinoma were treated with simple hysterectomy followed by HDR-IVRT alone at our institution. Comprehensive surgical staging (CSS), defined as pelvic washings and pelvic/paraaortic lymph node sampling, was performed in 20% of patients. The mean age was 60 years (range, 29-92 years). Lymphovascular invasion (LVI) was present in 14% of patients. The median HDR-IVRT dose was 21 Gy (range, 6-21 Gy), given in three fractions. Complications were assessed in terms of late Radiation Therapy Oncology Group (Grade 3 or worse) toxicity of the GI tract, genitourinary GU tract, and vagina. Results: With a median follow-up of 48 months, the 5-year vaginal/pelvic control rate was 95% (95% confidence interval [CI], 93-98%). On multivariate analysis, a poor vaginal/pelvic control rate correlated with age {>=}60 years old (relative risk [RR], 3, 95% CI, 1-12; p = 0.01), International Federation of Gynecology and Obstetrics (FIGO) Grade 3 (RR, 9, 95% CI, 2-35; p = 0.03), and LVI (RR, 4, 95% CI, 1-13; p = 0.051). The depth of myometrial invasion and CSS, however, were not significant. With regard to pelvic control specifically, the presence of GOG no. 99 HR features did not affect the pelvic control rate. The 5-year rate for HR patients was 96% (95% CI, 90-100%) vs. 96% (95% CI, 94-99%) for those without HR disease (p = 0.48). Even when the CSS effect was taken into account, the influence of HR features on pelvic control was still not significant (p = 0.51). In contrast, pelvic control was significantly influenced when patients were grouped according to CSS and stage/grade substages. For those with Stage IB Grade 3-IIB and no CSS, the 5-year pelvic control rate was 86% compared with 97% for those with Stage IB Grade 3-IIB and CSS, 97% for Stage IB, Grade 1-2 without CSS, and 100% for those with Stage IB, Grade 1-2 and CSS (p = 0.027). The 5-year disease-free survival rate was 93% (95% CI, 90-96%). On multivariate analysis, poor disease-free survival correlated with age {>=}60 years (RR, 5; 95% CI, 1-18; p = 0.002), FIGO Grade 3 (RR 5, 95% CI 2-17; p = 0.013), and LVI (RR 3, 95% CI 1-8; p 0.054). Unlike pelvic control, disease-free survival was significantly affected by GOG no. 99 HR features, with a 5-year rate of 87% (95% CI, 76-99%) vs. 94% (95% CI, 91-97%) for those without HR features (p = 0.027). The 5-year overall and disease-specific survival rate was 93% and 97%, respectively. The overall 5-year actuarial rate of Grade 3 or worse complications was 1% (95% CI, 0-2%). Conclusion: Tumor grade, depth of invasion, and the use of CSS were better predictors of pelvic control than the GOG no. 99 HR factors. IVRT alone seemed to provide adequate tumor control with very low morbidity. Therefore, it seems prudent to consider it for intermediate-risk patients because of its superior therapeutic ratio compared with that for surgery alone or pelvic RT. Additional follow-up, however, with a larger number of patients is needed, especially for those with LVI.« less

Improving the clinical management of women with borderline tumours: a recurrence risk scoring system from a French multicentre study.

PubMed

Ouldamer, L; Bendifallah, S; Nikpayam, M; Body, G; Fritel, X; Uzan, C; Morice, P; Daraï, E; Ballester, M

2017-05-01

To develop a risk scoring system (RSS) for predicting recurrence in women with borderline ovarian tumours (BOTs). Cohort study of women with BOTs. French multicentre tertiary care centres. A cohort of 360 women with BOTs who received primary surgical treatment between January 2000 and December 2013. Clinical and pathological factors affecting recurrence in women with BOTs. The development of a model for the prediction of recurrence in women with BOTs. Overall the recurrence rate was 20.0% (72/360). Recurrence was associated with five variables: age < 45 years; preoperative serum tumour marker CA125 > 150 IU/mL; a serous histological subtype; International Federation of Gynecology and Obstetrics (FIGO) stage other than IA; and ovarian surgery other than bilateral salpingo-oophorectomy (BSO; i.e. cystectomy and unilateral salpingo-oophorectomy). These variables were included in the RSS and assigned scores ranging from 0 to 6. The discrimination of the RSS was 0.82 (95% confidence interval, 95% CI 0.79-0.85). A total score of 8 points corresponded to the optimal threshold of the RSS, with a rate of recurrence of 11.8% (35/297) and 58.7% (37/63) for women at low risk (<8 points) and women at high risk (≥8 points), respectively. The diagnostic accuracy was 85.0%. This study shows that the risk of BOT recurrence can be accurately predicted so that women at high risk can benefit from adapted surgical treatment. Our RSS permitted women with BOTs at low risk to be distinguished from women with BOTs at high risk of recurrence. © 2017 Royal College of Obstetricians and Gynaecologists.

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients-Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group.

PubMed

Marnitz, Simone; Martus, Peter; Köhler, Christhardt; Stromberger, Carmen; Asse, Elke; Mallmann, Peter; Schmidberger, Heinz; Affonso Júnior, Renato José; Nunes, João Soares; Sehouli, Jalid; Budach, Volker

2016-02-01

The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique. A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and radiation technique. A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade ≥3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT. The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study. Copyright © 2016 Elsevier Inc. All rights reserved.

[Tandem transplantation with peripheral autologous hematopoietic blood stem cells in treatment of oncologic and hematologic malignancies. Initial results of the Donauspital, Vienna].

PubMed

Ruckser, R; Kier, P; Sebesta, C; Kittl, E; Kurz, M; Selleny, S; Höniger, S; Scherz, M; Habertheuer, K H; Zelenka, P

1995-01-01

10 patients were subjected to tandem transplantation for breast cancer (n = 3), ovarian cancer (n = 2) and multiple myeloma (n = 5), at the Second Department of Medicine, Donauspital, Vienna. The breast cancer patients were in stages 2 and 3, respectively, at diagnosis and entered complete remission thereafter. 2 of them developed lymph node metastasis and additional local recurrence, the 3rd patient presented with distant metastasis. The 2 patients with ovarian cancer were in stages Figo III and IV, respectively, at the time of diagnosis, and showed minimal residual disease at second-look-operation. 5 patients with multiple myeloma were in stage 3 pretransplant. Peripheral stem cells were obtained after either high-dose cyclophosphamide or FEC induction and application of cytokines. In 4 patients, tandem transplantation has been completed. 1 patient with multiple myeloma, who had received total body irradiation in combination with chemotherapy for the 2nd transplant, succumbed from idiopathic interstitial pneumonia. No severe clinical complications were observed in all other patients. All patients with solid tumors entered complete remission after the 1st transplantation. 3 of them completed tandem transplantation. Of these, 2 remain in continuous complete remission, the 3rd patient relapsed in lymph nodes day 485. In patients who received only 1 course of high dose chemotherapy with stem cell transplantation, relapses occurred on days 29 and 75, respectively. All patients with multiple myeloma entered only partial remission. We conclude that supralethal chemotherapy with peripheral blood stem cell support is a safe procedure that may at least induce prolonged remissions in solid tumors and hematologic malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Does a uterine manipulator affect cervical cancer pathology or identification of lymphovascular space involvement?

PubMed

Rakowski, Joseph A; Tran, Tien Anh N; Ahmad, Sarfraz; James, Jeffrey A; Brudie, Lorna A; Pernicone, Peter J; Radi, Michael J; Holloway, Robert W

2012-10-01

Uterine manipulators are a useful adjunct for robotic-assisted radical hysterectomy (RARH), but some surgeons avoid their use for fear of altering pathology or interpretation of lymphovascular space involvement (LVSI). We retrospectively compared clinico-pathological data and tumor pathology from patients with cervical cancer operated by laparotomy vs. RARH. Charts from cervical cancer patients who underwent radical hysterectomy from January-1997 to June-2010 were reviewed for tumor histology, grade, FIGO stage, lymph node status, LVSI, depth of invasion, and tumor size. A ConMed V-Care® uterine manipulator was used in all robotic cases. H&E stained slides from 20 robotic and 24 open stage IB1 cases with LVSI reported in the original pathology were re-reviewed by a blinded pathologist for analysis of tissue artifacts and LVSI. Two-hundred-thirty-six cases (185 open, 51 robotic) with stages IA2, IB1 and IB2 cervical cancer were reviewed. No significant differences in histology (squamous cell carcinoma, 65% vs. 51%; p=0.1), IB1 lesion size (≤2 cm, 62% vs. 61%, p>0.1), LVSI (34% vs. 39%, p>0.1), and depth of stromal invasion (p>0.1) was found between open and robotic groups. Histologic examination of all IB1 cervical carcinomas revealed a higher degree of surface disruption [45% (9/20) vs. 12.6% (3/24), p=0.038] and artifactual "parametrial carryover" [65% (13/20) vs. 29% (7/24), p=0.037] in robotic vs. open groups, respectively, but no significant differences in the rate of LVSI. RARH cases that utilized a uterine manipulator did not show any clinico-pathological differences in depth of invasion, LVSI, or parametrial involvement compared to open cases. Copyright © 2012 Elsevier Inc. All rights reserved.

Definition of compartment-based radical surgery in uterine cancer: radical hysterectomy in cervical cancer as 'total mesometrial resection (TMMR)' by M Höckel translated to robotic surgery (rTMMR).

PubMed

Kimmig, Rainer; Wimberger, Pauline; Buderath, Paul; Aktas, Bahriye; Iannaccone, Antonella; Heubner, Martin

2013-08-26

Radical hysterectomy has been developed as a standard treatment in Stage I and II cervical cancers with and without adjuvant therapy. However, there have been several attempts to standardize the technique of radical hysterectomy required for different tumor extension with variable success. Total mesometrial resection as ontogenetic compartment-based oncologic surgery - developed by open surgery - can be standardized identically for all patients with locally defined tumors. It appears to be promising for patients in terms of radicalness as well as complication rates. Robotic surgery may additionally reduce morbidity compared to open surgery. We describe robotically assisted total mesometrial resection (rTMMR) step by step in cervical cancer and present feasibility data from 26 patients. Patients (n = 26) with the diagnosis of cervical cancer were included. Patients were treated by robotic total mesometrial resection (rTMMR) and pelvic or pelvic/periaortic robotic therapeutic lymphadenectomy (rtLNE) for FIGO stage IA-IIB cervical cancer. No transition to open surgery was necessary. No intraoperative complications were noted. The postoperative complication rate was 23%. Within follow-up time (mean: 18 months) we noted one distant but no locoregional recurrence of cervical cancer. There were no deaths from cervical cancer during the observation period. We conclude that rTMMR and rtLNE is a feasible and safe technique for the treatment of compartment-defined cervical cancer.

CD44 expression in curettage and postoperative specimens of endometrial cancer.

PubMed

Wojciechowski, Michał; Krawczyk, Tomasz; Śmigielski, Janusz; Malinowski, Andrzej

2015-02-01

Adhesive molecules like CD44 are well defined key players in the metastatic cascade in many cancers, including endometrial cancer. They could play a role of markers of invasion, metastasis and prognostic factors. The aim of the study is to assess a possible role of the CD44 as a marker of invasion in endometrial cancer, both at the moment of preoperative workup and final staging. Available for analysis were archival specimens of 51 patients who had underwent curettage and surgery between 2002 and 2007. An immunohistochemical study for CD44 expression was performed in curettage and postoperative specimens. Normal endometrium of 20 randomly chosen patients was used as a control group. In endometrial cancer the expression of CD44 was significantly more intensive than in normal endometrium. In postoperative specimens, the CD44 expression was weaker in serous than in endometrioid cancer. There was no significant correlation between the adhesion molecule expression and clinicopathological features: grade,depth of invasion, cervical involvement, serosal and adnexal involvement, lymph-vascular space involvement, lymph node and distant metastases nor FIGO stage. An increased expression of CD44 in endometrial cancer suggests its possible role in pathogenesis of this disease, however, it doesn't seem to be crucial. Different expression of the CD44 in endometrioid and papillary-serous type may reflect different pathogenesis of these types of cancer. No statistically proved relation between the investigated molecule expression and clinicopathological parameters suggests scepticism about its use in diagnostic process of endometrial cancer.

The FIGO systems for nomenclature and classification of causes of abnormal uterine bleeding in the reproductive years: who needs them?

PubMed

Munro, Malcolm G; Critchley, Hilary O D; Fraser, Ian S

2012-10-01

In November 2010, the International Federation of Gynecology and Obstetrics formally accepted a new classification system for causes of abnormal uterine bleeding in the reproductive years. The system, based on the acronym PALM-COEIN (polyps, adenomyosis, leiomyoma, malignancy and hyperplasia-coagulopathy, ovulatory disorders, endometrial causes, iatrogenic, not classified) was developed in response to concerns about the design and interpretation of basic science and clinical investigation that relates to the problem of abnormal uterine bleeding. A system of nomenclature for the description of normal uterine bleeding and the various symptoms that comprise abnormal bleeding has also been included. This article describes the rationale, the structured methods that involved stakeholders worldwide, and the suggested use of the International Federation of Gynecology and Obstetrics system for research, education, and clinical care. Investigators in the field are encouraged to use the system in the design of their abnormal uterine bleeding-related research because it is an approach that should improve our understanding and management of this often perplexing clinical condition. Copyright © 2012. Published by Mosby, Inc.

Less versus more radical surgery in stage IB1 cervical cancer: A population-based study of long-term survival.

PubMed

Tseng, Jill H; Aloisi, Alessia; Sonoda, Yukio; Gardner, Ginger J; Zivanovic, Oliver; Abu-Rustum, Nadeem R; Leitao, Mario M

2018-05-15

Standard surgical treatment for women with stage IB1 cervical cancer consists of radical hysterectomy. This study assesses survival outcomes of those treated with less radical surgery (LRS; conization, trachelectomy, simple hysterectomy) compared to more radical surgery (MRS; modified radical, radical hysterectomy). Using the Surveillance, Epidemiology and End Results database, we identified women <45 years with FIGO stage IB1 cervical cancer diagnosed from 1/1998 to 12/2012. Only those who underwent lymph node (LN) assessment were analyzed. Disease-specific survivals (DSSs) of LRS were compared with those of MRS. Of 2571 patients, 807 underwent LRS and 1764 underwent MRS, all with LN assessment. For LRS vs. MRS, 28% vs. 23% were diagnosed with adenocarcinoma (p = 0.024), 31% vs. 39% had G3 disease (p < 0.001), 40% vs. 45% had tumor size >2 cm (p < 0.001), and 27% vs. 29% received adjuvant radiation therapy (p = 0.005). Median follow-up was 79 months (range, 0-179). Ten-year DSS for LRS vs. MRS was 93.5% vs. 92.3% (p = 0.511). There was no difference in 10-year DSS when stratified by tumor size ≤2 cm (LRS 95.1% vs. MRS 95.6%, p = 0.80) or > 2 cm (LRS 90.1% vs. MRS 88.2%, p = 0.48). Factors independently associated with increased risk of death included adenosquamous histology (HR 2.37), G3 disease (HR 2.86), tumors >2 cm (HR 1.82), and LN positivity (HR 2.42). Compared to MRS, LRS was not associated with a higher risk of death. In a select group of young women with stage IB1 cervical cancer, LRS compared to MRS does not appear to compromise DSS. Copyright © 2018 Elsevier Inc. All rights reserved.

Critical Imperative for the Reform of British Interpretation of Fetal Heart Rate Decelerations: Analysis of FIGO and NICE Guidelines, Post-Truth Foundations, Cognitive Fallacies, Myths and Occam's Razor.

PubMed

Sholapurkar, Shashikant L

2017-04-01

Cardiotocography (CTG) has disappointingly failed to show good predictability for fetal acidemia or neonatal outcomes in several large studies. A complete rethink of CTG interpretation will not be out of place. Fetal heart rate (FHR) decelerations are the most common deviations, benign as well as manifestation of impending fetal hypoxemia/acidemia, much more commonly than FHR baseline or variability. Their specific nomenclature is important (center-stage) because it provides the basic concepts and framework on which the complex "pattern recognition" of CTG interpretation by clinicians depends. Unfortunately, the discrimination of FHR decelerations seems to be muddled since the British obstetrics adopted the concept of vast majority of FHR decelerations being "variable" (cord-compression). With proliferation of confusing waveform criteria, "atypical variables" became the commonest cause of suspicious/pathological CTG. However, National Institute for Health and Care Excellence (NICE) (2014) had to disband the "typical" and "atypical" terminology because of flawed classifying criteria. This analytical review makes a strong case that there are major and fundamental framing and confirmation fallacies (not just biases) in interpretation of FHR decelerations by NICE (2014) and International Federation of Gynecology and Obstetrics (FIGO) (2015), probably the biggest in modern medicine. This "post-truth" approach is incompatible with scientific practice. Moreover, it amounts to setting oneself for failure. The inertia to change could be best described as "backfire effect". There is abundant evidence that head-compression (and other non-hypoxic mediators) causes rapid rather than shallow/gradual decelerations. Currently, the vast majority of decelerations are attributed to unproven cord compression underpinned by flawed disproven pathophysiological hypotheses. Their further discrimination based on abstract, random, trial and error criteria remains unresolved suggesting a false premise to begin with. This is not surprising considering that the commonest pathophysiology of intrapartum hypoxemia is contraction-induced reduction in uteroplacental perfusion (sometimes already compromised) and not cord compression at all. This distorted categorization causes confusion, false-alarm fatigue and difficulty in focusing on real pathological decelerations making CTG interpretation dysfunctional ultimately compromising patient safety. Obstetricians/midwives should demand reverting to the previous more scientific British categorization of decelerations based solely on time relationship to contractions as advocated by the pioneers like Hon and Caldeyro-Barcia, rather than accepting the current "post-truth" scenario.

Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms.

PubMed

Tafe, Laura J; Garg, Karuna; Chew, Ivy; Tornos, Carmen; Soslow, Robert A

2010-06-01

Carcinomas of the endometrium and ovary with undifferentiated components are uncommon neoplasms that are likely underdiagnosed. They are important to recognize as they have been shown to be clinically aggressive. We identified 32 carcinomas with undifferentiated components as defined by Silva and co-workers, 26 endometrial and 6 of ovarian origin. The patient age ranged from 21 to 76 years (median 55); 40% of patients were

Silencing of BAG3 inhibits the epithelial-mesenchymal transition in human cervical cancer.

PubMed

Song, Fei; Wang, Geng; Ma, Zhifang; Ma, Yuebing; Wang, Yingying

2017-11-10

Bcl2-associated athanogene 3 (BAG3) has been reported to be involved in aggressive progression of many tumors. In the present study, we examined the expression of BAG3 in human cervical cancer (CC) tissues and investigated the role of BAG3 in SiHa and HeLa cell growth, migration, and invasion. Here, we found that most of CC tissues highly expressed the protein and mRNA of BAG3, while their expression was obviously lower in paired normal tissues (all p<0.001). BAG3 expression was associated with FIGO stage and metastasis (all p<0.05). In-vitro analysis demonstrated that BAG3 siRNAs inhibited SiHa and HeLa cell growth, invasion and migration. Mechanically, BAG3 siRNAs inhibited the expression of EMT-regulating markers, involving MMP2, Slug and N-cadherin, and increased the expression of E-cadherin. In a xenograft nude model, BAG3 siRNAs inhibited tumor growth and the expression of EMT biomarkers. In conclusion, BAG3 is involved in the EMT process, including cell growth, invasion and migration in the development of CC. Thus, BAG3 target might be recommended as a novel therapeutic approach.

Silencing of BAG3 inhibits the epithelial-mesenchymal transition in human cervical cancer

PubMed Central

Song, Fei; Wang, Geng; Ma, Zhifang; Ma, Yuebing; Wang, Yingying

2017-01-01

Bcl2-associated athanogene 3 (BAG3) has been reported to be involved in aggressive progression of many tumors. In the present study, we examined the expression of BAG3 in human cervical cancer (CC) tissues and investigated the role of BAG3 in SiHa and HeLa cell growth, migration, and invasion. Here, we found that most of CC tissues highly expressed the protein and mRNA of BAG3, while their expression was obviously lower in paired normal tissues (all p<0.001). BAG3 expression was associated with FIGO stage and metastasis (all p<0.05). In-vitro analysis demonstrated that BAG3 siRNAs inhibited SiHa and HeLa cell growth, invasion and migration. Mechanically, BAG3 siRNAs inhibited the expression of EMT-regulating markers, involving MMP2, Slug and N-cadherin, and increased the expression of E-cadherin. In a xenograft nude model, BAG3 siRNAs inhibited tumor growth and the expression of EMT biomarkers. In conclusion, BAG3 is involved in the EMT process, including cell growth, invasion and migration in the development of CC. Thus, BAG3 target might be recommended as a novel therapeutic approach. PMID:29221135

Long-term follow-up of patients with an isolated ovarian recurrence after conservative treatment of epithelial ovarian cancer: review of the results of an international multicenter study comprising 545 patients.

PubMed

Bentivegna, Enrica; Fruscio, Robert; Roussin, Stephanie; Ceppi, Lorenzo; Satoh, Toyomi; Kajiyama, Hiroaki; Uzan, Catherine; Colombo, Nicoletta; Gouy, Sebastien; Morice, Philippe

2015-11-01

To determine the long-term outcomes of patients with an isolated ovarian recurrence after fertility sparing surgery (FSS) for epithelial ovarian cancer (EOC) and to evaluate the recurrence rates (and location) according to the new 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system. Retrospective multicenter study. Teams having reported recurrence after FSS for EOC. Four series comprising 545 patients undergoing FSS and 63 (12%) recurrences. FSS (salpingo-oophorectomy for a majority of cases) for EOC. Recurrences rates and characteristics of recurrent disease. Among 63 recurrent patients, 24 (38%) recurrences were isolated on the spared ovary, and 39 (62%) arose at an extraovarian site. Among the patients with an isolated ovarian recurrence, three patients died after a median follow-up period of 186 months (range: 28-294 months). Among the patients with recurrent extraovarian disease, 24 died and 7 were alive with persistent disease after a median follow-up period of 34 months (range: 3-231 months). The overall rate of isolated ovarian and extrapelvic recurrences was higher for grade 3 tumors (compared with grades 1/2). The long-term survival of patients with an isolated ovarian recurrence after FSS for EOC remains favorable. The prognosis of patients with an extraovarian recurrence is poor compared with those who have an isolated recurrent ovarian tumor. Grade 3 tumors (compared to grades 1/2) give rise to a higher rate of extraovarian recurrences. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Prognostic effect of isolated paraaortic nodal spread in endometrial cancer.

PubMed

Türkmen, Osman; Başaran, Derman; Karalok, Alper; Cömert Kimyon, Günsu; Taşçı, Tolga; Üreyen, Işın; Tulunay, Gökhan; Turan, Taner

2018-03-28

To evaluate the prognostic effect of isolated paraaortic lymph node metastasis in endometrial cancer (EC). This retrospective study included patients with FIGO 2009 stage IIIC2 disease due to isolated paraaortic lymph node metastasis (LNM). Patients with sarcomatous histology, synchronous gynecologic cancers and patients with concurrent pelvic lymph node metastases or patients that have intraabdominal tumor spread were excluded. Kaplan-Meier method was used for calculation of progression free survival (PFS) and overall survival. 1614 patients were operated for EC during study period.961 patients underwent lymph node dissection and 25 (2.6%) were found to have isolated LNM in paraaortic region and these constituted the study cohort.20 (80%) patients had endometrioid EC. Median number of retrieved lymph nodes from pelvic region and paraaortic region was 21.5 (range; 5-41) and 34.5 (range; 1-65), respectively. Median number of metastatic paraaortic nodes was 1 (range; 1-32).The median follow-up time was 15 months (range 5-94). 7 (28%) patients recurred after a median of 20 months (range, 3-99) from initial surgery. 3 patients recurred only in pelvis, one patient had upper abdominal spread and 3 had isolated extraabdominal recurrence.İnvolvement of uterine serosa, positive peritoneal cytology and presence of adnexal metastasis were significantly associated with diminished PFS (p<0.05). The presence of serosal involvement or adnexal involvement is as important as gross peritoneal spread and is related with poor survival in patients with isolated paraaortic nodal spread in EC. Chemotherapy should be the mainstay of treatment in this patient cohort which may eradicate systemic tumor spread.

Concomitant endometriosis in malignant and borderline ovarian tumours.

PubMed

Oral, Engin; Aydin, Ovgu; Kumbak, Banu Aygun; İlvan, Sennur; Yilmaz, Handan; Tustas, Esra; Bese, Tugan; Demirkiran, Fuat; Arvas, Macit

2018-06-08

The aim of the study was to reveal the prevalence of concomitant endometriosis in malignant and borderline ovarian tumours. A retrospective analysis was performed of 530 patients with malignant ovarian tumours and 131 with borderline ovarian tumours, who underwent surgery in our hospital between 1995 and 2011. Forty-eight (7.3%) of 661 patients with malignant and borderline ovarian tumours were associated with endometriosis. Of the 48 endometriosis cases, 73% of those were atypical. Infertility was noted in 38% of patients with endometriosis-associated ovarian tumours. The most frequently endometriosis-associated subtypes were endometrioid (33%) and clear cell (18%) histologies. Of endometriosis-associated endometrioid and clear cell ovarian tumours, 70% were early stage and 60% were premenopausal. The prevalence of concomitant endometriosis in borderline tumours (12%) was found to be significantly higher than that found in the malignant ones (6%; p = .02). Of 32 endometriosis-associated malignant ovarian tumours, 69% were FIGO stages I and II. In conclusion, ovarian endometriosis is seen with both malignant and borderline ovarian tumours, the association being significant with borderline tumours. Fortunately, the endometriosis-associated malignant ovarian tumours are mostly early stage. Impact statement What is already known on this subject? Epidemiologic data suggest that endometriosis has malignant potential. However, a subgroup of women with endometriosis at a high risk for ovarian cancer is yet to be clarified. Currently, endometriosis and ovarian cancer association does not seem to have a clinical implication. What do the results of this study add? The findings of this study revealed that nearly 75% of endometriosis-associated ovarian tumours were of atypical endometriosis. Half of endometriosis-associated ovarian tumour cases were of endometrioid/clear cell histology and 70% were early-stage. Endometriosis was significantly associated with borderline ovarian tumours and the endometriosis-associated malignant ovarian tumours were mostly early stage. What are the implications of these findings for clinical practice and/or further research? Additional studies need to be conducted to develop screening approaches for malignant transformation or an association in women with endometriosis. Till that time, a change of current clinical practices cannot be justified. However, counselling and treating women with endometriosis who are at high risk for cancer coexistence or conversion is encouraged.

ABO Blood Group and Endometrial Carcinoma: A Preliminary Single-Center Experience from Saudi Arabia.

PubMed

Abu-Zaid, Ahmed; Alsabban, Mohannad; Abuzaid, Mohammed; Alomar, Osama; Al-Badawi, Ismail A; Salem, Hany

2017-12-18

Inherited ABO blood groups have been shown to play possible contributions in the pathogenesis of various gynecologic and non-gynecologic carcinomas. With regard to gynecologic carcinomas, there is a confined number of studies that explored the relationship between ABO blood group and endometrial carcinoma (EC) in the PubMed-indexed literature. To the best of our knowledge, no such study has ever been conducted in Saudi Arabia. Our study has two objectives: (I) to determine the prevalence of ABO blood groups among Saudi patients with EC, and (II) to explore the relationship between ABO blood group and several clinico-pathological prognostic parameters (namely: menopausal status [age], body mass index [BMI], tumor grade, FIGO [Fédération Internationale de Gynécologie et d'Obstétrique] stage and recurrence) in Saudi patients with EC. A retrospective cross-sectional study from 01-January-2010 to 31-July-2014 was conducted at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia - a referral tertiary healthcare institute. One-hundred and fourteen patients (n=114) were included in the study. Clinico-pathological data were extrapolated from medical records, and their association with ABO blood groups were evaluated. Categorical data were presented as number of cases (n) and percentages (%). Two-tailed Chi-square test was used for univariate analysis. For all purposes, p values <0.05 were regarded as statistically significant. The mean age and BMI were 59.5 ± 10.8 years (range: 31 - 90) and 36.6 ± 8.6 kg/m 2 (range: 17 - 60), respectively. The vast majority of patients were post-menopausal (86%), had BMI >28 kg/m 2 (84.2%), diagnosed with early FIGO stage I-II (76.3%) and developed no recurrence (86.8%). The frequencies of ABO blood group types A, B, AB, and O were 28.1%, 12.3%, 3.5% and 56.1%, respectively. When ABO blood groups were analyzed as four different types (A, B, AB and O), O-type was the most common ABO blood group in pre- and post-menopausal EC patients (43.8% and 58.2%, respectively; p=0.14). There were no statistically significant correlations between ABO blood groups and all the examined clinico-pathological factors. Moreover, when ABO blood groups were analyzed as two different types (O and non-O), similar results were obtained; no statistically significant correlations were found between ABO blood groups and all the examined clinico-pathological factors.  O-type was the most prevalent ABO blood group among Saudi Arabian patients with EC, and our finding was different from the existing literature, probably highlighting an ethnic-related variance. Furthermore, no statistically significant correlations were identified between ABO blood groups and all the examined clinico-pathological factors. Also, routine ABO blood group may emerge as a clinically accessible, beneficial and economical biomarker for a possible EC vulnerability. A large-sized case-control study is needed to withdraw solid conclusions.

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients—Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marnitz, Simone, E-mail: simone.marnitz-schulze@uk-koeln.de; Martus, Peter; Köhler, Christhardt

Purpose: The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique. Methods and Materials: A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratifiedmore » by treatment arm and radiation technique. Results: A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade ≥3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT. Conclusions: The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study.« less

Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma

PubMed Central

Galaal, Khadra; Godfrey, Keith; Naik, Raj; Kucukmetin, Ali; Bryant, Andrew

2014-01-01

Background Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of patients with advanced uterine carcinosarcoma is poor with pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence. Objectives To evaluate the effectiveness and safety of radiotherapy and/or systemic chemotherapy in the management of stage III-IV persistent or recurrent uterine carcinosarcoma. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL, The Cochrane Library 2010, Issue 2, MEDLINE and EMBASE to May 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma. Data collection and analysis We independently abstracted data and assessed risk of bias. We pooled hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy in meta-analyses. Main results Three trials (579 women, of whom all were assessed at the end of the trials) met the inclusion criteria. Two trials (373 women with stage III-IV persistent or recurrent disease) found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide. There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, which affected significantly more women in the combination therapy group than in the ifosamide group. One trial found no statistically significant difference in the risk of death and disease progression in women who received whole abdominal irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95% CI 0.48 to 1.05 and HR = 0.79, 95% CI 0.53 to 1.18 for overall survival and progression-free survival respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, which affected significantly fewer women in the whole body irradiation group than in the chemotherapy group (RR = 0.02, 95% CI 0.00 to 0.16). Authors’ conclusions The results of this review are limited to two trials. In the primary treatment/first line therapy of advanced stage metastatic uterine carcinosarcoma, as well as in recurrent disease, adjuvant combination chemotherapy with ifosfamide and paclitaxel should be considered. None of the included studies reported on quality of life. PMID:21249682

Association between developmental steps in the organogenesis of the uterine cervix and locoregional progression of cervical cancer: a prospective clinicopathological analysis.

PubMed

Höckel, Michael; Hentschel, Bettina; Horn, Lars-Christian

2014-04-01

Our previous work provided evidence that early cervical cancer is locally confined to the Müllerian compartment that develops in women from the embryonic paramesonephric-mesonephric complex. We aimed to investigate if the concept of tumour permeation within ontogenetic domains is also valid for tumour progression and advanced disease. Starting from Carnegie stage 13, four successive steps in the organogenesis of the human uterine cervix were defined and an ontogenetic staging system for cervical cancer based on organ development was described. Histopathological and clinical data of patients with cervical cancer FIGO stages IB-IVA were raised prospectively from Oct 16, 1999, until Dec 20, 2012, and from March 8, 2000, until April 4, 2013, for two surgical trials of ontogenetic compartment resection without adjuvant radiation at the University of Leipzig (total or extended mesometrial resection [TMMR or EMMR]; and [laterally] extended endopelvic resection [LEER]). The primary endpoints of these trials were pathological resection state and locoregional tumour control. Patients who underwent TMMR and EMMR had follow-up assessment every 3-6 months for 5 years, and yearly thereafter. Patients who had (L)EER, every 3-6 months for 10 years, and yearly thereafter. By analysing the presence of disease within the classified tissues and disease outcome in these patients, and by examining relapse patterns, we were able to observe whether surgical excision within developmental compartments was sufficient for disease control. Survival curves were compared using the log-rank test. The effect of ontogenetic tumour stage and pathological tumour stage on overall survival was assessed by Cox proportional hazard models. The trials are registered as an ongoing observational monocentric study at the University of Leipzig Cancer Centre (ULCC012-13-28012013). 367 patients were included in our analysis. Staged organogenesis of the uterine cervix and progressive local growth of cervical carcinoma occur in the same tissue domains. The neoplasm originating in the uterine cervix, ontogenetic tumour stage 1 (oT1, n=217), permeates successively during its malignant progression the tissues developed from the Müllerian compartment (oT2, n=101), the genital metacompartment (oT3, n=38), and the urogenitorectal metacompartment (oT4, n=11). Ontogenetic staging, when comparing patients with oT1 and oT2 disease to those with oT3 and oT4 disease (hazard ratio 5·9, 95% CI 2·2-15·5; p=0·00036) was a better prognostic indicator for survival than pathological staging when comparing pT1b and pT2a with pT2b and pT4 disease (2·0, 95% CI 0·7-5·5; p=0·170). Resection of the stage-related ontogenetically specified tissue domains and their associated regional lymphoid tissues achieved an R0 resection in 363 (99%) of 367 patients and locoregional tumour control at 5 years was 94% (95% CI 92-97). 13 patients had grade 3 or 4 adverse events, the majority of which were urinary (10, 77%). Cervical cancer infiltrates the adult tissues established during ontogeny, pursuing the developmental steps in retrograde sequence. Clinical translation of these insights into ontogenetic tumour staging and compartment resection holds the potential to improve prognostic assessment and curative treatment. University of Leipzig and Leipzig School of Radical Pelvic Surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adrenal Metastasis from Uterine Papillary Serous Carcinoma.

PubMed

Singh Lubana, Sandeep; Singh, Navdeep; Tuli, Sandeep S; Seligman, Barbara

2016-04-27

Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case.

Vulvar cancer: the Cinderella of gynaecological oncology.

PubMed

Giles, G G; Kneale, B L

1995-02-01

Cancer of the vulva is a rare malignancy that increases progressively with age. The age-standardized incidence averages between 1 and 2 per 100,000 women in Western countries. The majority (80-90%) are squamous cell carcinomas, melanoma and adenocarcinoma each accounting for about 5% of cases. Internationally, the incidence of vulvar cancer varies more than 30-fold, the highest rates being seen in populations of Portuguese South America. In many populations the incidence appears to be stable but there is some evidence that the incidence of in situ carcinoma is increasing in the United States of America. Epidemiological studies have identified sexual factors, particularly human papilloma virus (HPV) infection, as increasing risk. Smoking also increases risk by interacting synergistically with HPV infection and genital warts. The aetiologies of vulvar intraepithelial neoplasia (VIN)3/in situ disease and invasive cancer appear to differ. VIN does not automatically progress to invasive cancer and is strongly associated with HPV infection. Many older women with invasive vulvar cancer do not have evidence of HPV and do not smoke. More research is needed on the cause of vulvar carcinoma in this group. Treatment has become more conservative over the years and this has reduced morbidity and probably mortality. Although FIGO data do not show much by way of improvement in survival, data from population-based cancer registries have shown definite increases in survival (5-year survival proportions in excess of 80%, when age and Stage have been taken into account). Improvement is particularly related to the preponderance of early stage disease.

B3GNT3 Expression Is a Novel Marker Correlated with Pelvic Lymph Node Metastasis and Poor Clinical Outcome in Early-Stage Cervical Cancer

PubMed Central

Niu, Chunhao; Song, Libing; Zhang, Yanna

2015-01-01

Background The β1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) encodes a member of the B3GNT family that functions as the backbone structure of dimeric sialyl-Lewis A and is involved in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. B3GNT3 has been implicated as an important element in the development of certain cancers. However, the characteristics of B3GNT3 in the development and progression of cancer remain largely unknown. Thus, our study aimed to investigate the expression pattern and the prognostic value of B3GNT3 in patients with early-stage cervical cancer. Methods The mRNA and protein levels of B3GNT3 expression were examined in eight cervical cancer cell lines and ten paired cervical cancer tumors, using real-time PCR and western blotting, respectively. Immunohistochemistry (IHC) was used to analyze B3GNT3 protein expression in paraffin-embedded tissues from 196 early-stage cervical cancer patients. Statistical analyses were applied to evaluate the association between B3GNT3 expression scores and clinical parameters, as well as patient survival. Results B3GNT3 expression was significantly upregulated in cervical cancer cell lines and lesions compared with normal cells and adjacent noncancerous cervical tissues. In the 196 cases of tested early-stage cervical cancer samples, the B3GNT3 protein level was positively correlated with high risk TYPES of human papillomavirus (HPV) infection (P = 0.026), FIGO stage (P < 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P < 0.001), concurrent chemotherapy and radiotherapy (P = 0.016), lymphovascular space involvement (P = 0.003) and most importantly, lymph node metastasis (P = 0.003). Patients with high B3GNT3 expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with those with low expression of this protein. Multivariate analysis suggested that B3GNT3 expression is an independent prognostic indicator for cervical cancer patients. Conclusions Our study demonstrated that elevated B3GNT3 expression is associated with pelvic lymph node metastasis and poor outcome in early-stage cervical cancer patients. B3GNT3 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer. PMID:26709519

Abnormal uterine bleeding: advantages of formal classification to patients, clinicians and researchers.

PubMed

Madhra, Mayank; Fraser, Ian S; Munro, Malcolm G; Critchley, Hilary O D

2014-07-01

To highlight the advantages of formal classification of causes of abnormal uterine bleeding from a clinical and scientific perspective. Review and recommendations for local implementation. In the past, research in the field of menstrual disorders has not been funded adequately with respect to the impact of symptoms on individuals, healthcare systems and society. This was confounded by a diverse terminology, which lead to confusion between clinical and scientific groups, ultimately harming the underlying evidence base. To address this, a formal classification system (PALM-COEIN) for the causes of abnormal uterine bleeding has been published for worldwide use by FIGO (International Federation of Gynecology and Obstetrics). This commentary explains problems created by the prior absence of such a system, the potential advantages stemming from its use, and practical suggestions for local implementation. The PALM-COEIN classification is applicable globally and, as momentum gathers, will ameliorate recurrence of historic problems, and harmonise reporting of clinical and scientific research to facilitate future progress in women's health. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

A specific immune and lymphatic profile characterizes the pre-metastatic state of the sentinel lymph node in patients with early cervical cancer

PubMed Central

Balsat, Cédric; Blacher, Silvia; Herfs, Michael; Van de Velde, Maureen; Signolle, Nicolas; Sauthier, Philippe; Pottier, Charles; Gofflot, Stéphanie; De Cuypere, Marjolein; Delvenne, Philippe; Goffin, Frédéric; Noel, Agnès; Kridelka, Frédéric

2017-01-01

ABSTRACT The lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms. An original digital image analysis methodology was used to objectively determine whole slide densities and spatial distributions of immunostained structures. We observed a marked increase in lymphatic vessel density (LVD) and a specific capsular and subcapsular distribution in pre-metastatic SLN when compared with non-sentinel counterparts. Such features persisted in the presence of nodal metastatic colonization. The inflammatory profile attested by CD8+, Foxp3, CD20 and PD-1expression was also significantly increased in pre-metastatic SLN. Remarkably, the densities of CD20+ B cells and PD-1 expressing germinal centers were positively correlated with LVD. All together, these data strongly support the existence of a pre-metastatic dialog between the primary tumor and the first nodal relay. Both lymphatic and immune responses contribute to the elaboration of a specific pre-metastatic microenvironment in human SLN. Moreover, this work provides evidence that, in the context of early cervical cancer, a pre-metastatic lymphangiogenesis occurs within the SLN (pre-metastatic niche) and is associated with a specific humoral immune response. PMID:28344873

The Influence of Radiation Modality and Lymph Node Dissection on Survival in Early-Stage Endometrial Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chino, Junzo P., E-mail: junzo.chino@duke.edu; Jones, Ellen; Berchuck, Andrew

2012-04-01

Background: The appropriate uses of lymph node dissection (LND) and adjuvant radiation therapy (RT) for Stage I endometrial cancer are controversial. We explored the impact of specific RT modalities (whole pelvic RT [WPRT], vaginal brachytherapy [VB]) and LND status on survival. Materials and Methods: The Surveillance Epidemiology and End Results dataset was queried for all surgically treated International Federation of Gynecology and Obstetrics (FIGO) Stage I endometrial cancers; subjects were stratified into low, intermediate and high risk cohorts using modifications of Gynecologic Oncology Group (GOG) protocol 99 and PORTEC (Postoperative Radiation Therapy in Endometrial Cancer) trial criteria. Five-year overall survivalmore » was estimated, and comparisons were performed via the log-rank test. Results: A total of 56,360 patients were identified: 70.4% low, 26.2% intermediate, and 3.4% high risk. A total of 41.6% underwent LND and 17.6% adjuvant RT. In low-risk disease, LND was associated with higher survival (93.7 LND vs. 92.7% no LND, p < 0.001), whereas RT was not (91.6% RT vs. 92.9% no RT, p = 0.23). In intermediate-risk disease, LND (82.1% LND vs. 76.5% no LND, p < 0.001) and RT (80.6% RT vs. 74.9% no RT, p < 0.001) were associated with higher survival without differences between RT modalities. In high-risk disease, LND (68.8% LND vs. 54.1% no LND, p < 0.001) and RT (66.9% RT vs. 57.2% no RT, p < 0.001) were associated with increased survival; if LND was not performed, VB alone was inferior to WPRT (p = 0.01). Conclusion: Both WPRT and VB alone are associated with increased survival in the intermediate-risk group. In the high-risk group, in the absence of LND, only WPRT is associated with increased survival. LND was also associated with increased survival.« less

Overcoming extreme obesity with robotic surgery.

PubMed

Stone, Pamela; Burnett, Alexander; Burton, Brian; Roman, Juan

2010-12-01

Obesity is often associated with endometrial cancer and has posed a challenge in surgical management. Complications such as wound breakdown, respiratory challenges, cardiac complications and difficult intubations are associated with obesity. For the patient with uterine cancer, surgery is necessary for staging, control of symptoms and cure. With the advent of the da Vinci(™) intuitive robot, alternative surgical options can now be offered to these patients. While surgery is the principal modality for the treatment and management of uterine cancer, the morbidly obese patient faces increased complications and longer postoperative recovery. As studied in the LAP2, comparable outcomes have been noted in laparotomy vs laparoscopic surgery. Recently, minimally invasive surgery has been refined with the advent of the da Vinci robotic system. Applying a minimally invasive technique further enhanced with the da Vinci robotic system, a total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed on a patient with a BMI of 98. A 35 year-old G0 woman with a BMI of 98 presented with heavy vaginal bleeding and anaemia. She was diagnosed with endometrioid adenocarcinoma of the uterus, FIGO grade 1. She was treated with a robotically assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. Her postoperative course was uncomplicated and she was discharged home on post-operative day 1. Since obesity is a significant risk factor for endometrial cancer and the prevalence of obesity is increasing, developing surgical techniques to appropriately manage these patients is important. Minimally invasive surgery, specifically with robotic assistance, has increased the possibilities of performing minimally invasive surgery in morbidly obese women. It allows navigation around anatomical barriers and decreases the fatigue experienced by the surgeons. With the increasing obesity of our population and the high prevalence of uterine cancer, further advancement of equipment, anaesthesia and surgical techniques to accommodate the larger patient while decreasing complications have yet to be standardized. Copyright © 2010 John Wiley & Sons, Ltd.

Facing the noncommunicable disease (NCD) global epidemic--the battle of prevention starts in utero--the FIGO challenge.

PubMed

Roura, Lluis Cabero; Arulkumaran, Sir Sabaratnam

2015-01-01

Noncommunicable diseases (NCDs) are responsible for 36 million deaths every year. Of this death toll, nearly 80% (29 million) occur in low- and median-income countries. More than 9 million deaths attributed to NCDs occur in people under 60 years of age. National economies are suffering considerable losses due to premature death or disability to work resulting from heart disease, stroke, and diabetes. The knowledge that in utero and in early childhood certain processes can affect the risk of developing NCDs provides an opportunity to enforce interventions during this critical time, when they may have the greatest effect. Using appropriate protocols, the health-care provider can educate mothers about the risks of certain nutritional and environmental exposures and integrate health promotion on the agenda, as part of the social and economic development. All this could motivate a substantial reduction in the risk of NCDs. Current and future health challenges demand new and changing competencies that should form the basis for education, training, and workforce planning. The International Federation of Gynaecology and Obstetrics (FIGO) is aware of that responsibility and has joined hands with other agencies and organizations that make a considerable effort in providing appropriate prenatal care programs to prevent and treat most of the common preconditioning factors, especially in low-income countries. Copyright © 2014 Elsevier Ltd. All rights reserved.

ESR1 gene amplification in endometrial carcinomas: a clinicopathological analysis.

PubMed

Rahman, Mohammed Tanjimur; Nakayama, Kentaro; Rahman, Munmun; Ishikawa, Masako; Katagiri, Hiroshi; Katagiri, Atsuko; Ishibashi, Tomoka; Sato, Emi; Iida, Kouji; Ishikawa, Noriyuki; Nakayama, Naomi; Miyazaki, Kohji

2013-09-01

This study investigated the clinicopathological significance of estrogen receptor 1 (ESR1) gene amplification and its relationship to phosphatase and tensin homolog (PTEN), human epidermal growth factor receptor 2 (HER2), MutL homolog 1 (MLH1), p53, and AT rich interactive domain 1A (ARID1A) expression in endometrial carcinomas. ESR1 amplification and expression were assessed by fluorescence in situ hybridization and immunohistochemistry. Clinical data were collected by retrospective chart review. ESR1 amplification was identified in 13 out of 111 (11.7%) endometrial carcinomas. No significant association was observed between ESR1 amplification and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.17), histological grade (p=0.35), lymph node metastasis (p=0.51), or deep myometrial invasion (p=0.46). ESR1 amplification was independent of PTEN, p53, HER2, MLH1, and ARID1A protein expression. Patients without estrogen receptor (ER) or progesterone receptor (PR) expression had shorter progression-free and overall survival than those with ER or PR expression (p<0.01). ESR1 amplification is independent of known clinicopathological factors related to poor prognosis and PTEN, p53, HER2, MLH1, and ARID1A protein expression, suggesting ESR1 amplification may be an early event in endometrial carcinoma development.

Implementation of image-guided brachytherapy (IGBT) for patients with uterine cervix cancer: a tumor volume kinetics approach.

PubMed

Carvalho, Heloisa de Andrade; Mendez, Lucas Castro; Stuart, Silvia Radwanski; Guimarães, Roger Guilherme Rodrigues; Ramos, Clarissa Cerchi Angotti; de Paula, Lucas Assad; de Sales, Camila Pessoa; Chen, André Tsin Chih; Blasbalg, Roberto; Baroni, Ronaldo Hueb

2016-08-01

To evaluate tumor shrinking kinetics in order to implement image-guided brachytherapy (IGBT) for the treatment of patients with cervix cancer. This study has prospectively evaluated tumor shrinking kinetics of thirteen patients with uterine cervix cancer treated with combined chemoradiation. Four high dose rate brachytherapy fractions were delivered during the course of pelvic external beam radiation therapy (EBRT). Magnetic resonance imaging (MRI) exams were acquired at diagnosis (D), first (B1), and third (B3) brachytherapy fractions. Target volumes (GTV and HR-CTV) were calculated by both the ellipsoid formula (VE) and MRI contouring (VC), which were defined by a consensus between at least two radiation oncologists and a pelvic expert radiologist. Most enrolled patients had squamous cell carcinoma and FIGO stage IIB disease, and initiated brachytherapy after the third week of pelvic external beam radiation. Gross tumor volume volume reduction from diagnostic MRI to B1 represented 61.9% and 75.2% of the initial volume, when measured by VE and VC, respectively. Only a modest volume reduction (15-20%) was observed from B1 to B3. The most expressive tumor shrinking occurred in the first three weeks of oncological treatment and was in accordance with gynecological examination. These findings may help in IGBT implementation.

A Case of Lymphoepithelioma-like Carcinoma in the Uterine Cervix.

PubMed

Takebayashi, Kanetoshi; Nishida, Masakazu; Matsumoto, Harunobu; Nasu, Kaei; Narahara, Hisashi

2015-02-11

Lymphoepithelioma-like carcinoma occurring in the reproductive organs is a rare variant of squamous cell carcinoma, and this tumor of the uterine cervix accounts for 0.7% of all primary cervical uterine neoplasms. Associations with Epstein-Barr virus (EBV) and human papilloma virus (HPV) have been demonstrated in some studies. Some investigators suggested that EBV has an important role in the initiation of lymphoepitheliomalike carcinoma in Asian women. Here we report the case of a 45-year-old Japanese woman, gravida 2 and parity 2. She was admitted due to severe atypical genital bleeding caused by uterine cervical cancer. A >60-mm tumor was detected at the uterine cervix, and no distal metastasis or swallowing of lymph nodes was revealed by magnetic resonance imaging and a computed tomography scan. The cervical cancer stage FIGO Ib2 was diagnosed, and a radical hysterectomy was performed for this malignant tumor. The in situ hybridization for EBV was negative. HVP infection was strongly suspected because the squamous cell carcinoma was observed macroscopically in the uterine cervix. The prognosis of uterine lymphoepithelioma-like carcinoma is thought to be better than those of other cervical cancer types, but careful follow-up at fixed intervals is recommended. The patient has been followed up for 4 months since her surgery, and no evidence of recurrence has been detected.

Downregulation of SASH1 correlates with poor prognosis in cervical cancer.

PubMed

Xie, J; Zhang, W; Zhang, J; Lv, Q-Y; Luan, Y-F

2017-10-01

The aim of this study was to analyze the association of SASH1 expression with clinicopathological features and prognosis in patients suffering cervical cancer. The expressions of SASH1 mRNA and protein in cervical cancer tissues and matched normal cervical tissues were detected by Real-time PCR and Immunohistochemistry. Based on the above findings, the association among SASH1 expression and clinicopathological features was analyzed. Overall survival was evaluated using the Kaplan-Meier method. The variables were used in univariate and multivariate analysis by the Cox proportional hazards model. The results demonstrated that both SASH1 mRNA and proteins were downregulated in cervical cancer tissues compared with those in matched normal tissues (both p < 0.05). Also, decreased SASH1 expression in cervical cancer was found to be significantly associated with high FIGO Stage (p = 0.001), lymph nodes metastasis (p = 0.003) and differentiation (p = 0.018). Furthermore, Kaplan-Meier analysis demonstrated that low SASH1 expression level was associated with poorer overall survival (p < 0.01). Univariate and multivariate analyses indicated that status of SASH1 was an independent prognostic factor for patients with cervical cancer. These findings suggested that SASH1 can be useful as a new prognostic marker and therapeutic target in cervical cancer patients.

Critical Imperative for the Reform of British Interpretation of Fetal Heart Rate Decelerations: Analysis of FIGO and NICE Guidelines, Post-Truth Foundations, Cognitive Fallacies, Myths and Occam’s Razor

PubMed Central

Sholapurkar, Shashikant L.

2017-01-01

Cardiotocography (CTG) has disappointingly failed to show good predictability for fetal acidemia or neonatal outcomes in several large studies. A complete rethink of CTG interpretation will not be out of place. Fetal heart rate (FHR) decelerations are the most common deviations, benign as well as manifestation of impending fetal hypoxemia/acidemia, much more commonly than FHR baseline or variability. Their specific nomenclature is important (center-stage) because it provides the basic concepts and framework on which the complex “pattern recognition” of CTG interpretation by clinicians depends. Unfortunately, the discrimination of FHR decelerations seems to be muddled since the British obstetrics adopted the concept of vast majority of FHR decelerations being “variable” (cord-compression). With proliferation of confusing waveform criteria, “atypical variables” became the commonest cause of suspicious/pathological CTG. However, National Institute for Health and Care Excellence (NICE) (2014) had to disband the “typical” and “atypical” terminology because of flawed classifying criteria. This analytical review makes a strong case that there are major and fundamental framing and confirmation fallacies (not just biases) in interpretation of FHR decelerations by NICE (2014) and International Federation of Gynecology and Obstetrics (FIGO) (2015), probably the biggest in modern medicine. This “post-truth” approach is incompatible with scientific practice. Moreover, it amounts to setting oneself for failure. The inertia to change could be best described as “backfire effect”. There is abundant evidence that head-compression (and other non-hypoxic mediators) causes rapid rather than shallow/gradual decelerations. Currently, the vast majority of decelerations are attributed to unproven cord compression underpinned by flawed disproven pathophysiological hypotheses. Their further discrimination based on abstract, random, trial and error criteria remains unresolved suggesting a false premise to begin with. This is not surprising considering that the commonest pathophysiology of intrapartum hypoxemia is contraction-induced reduction in uteroplacental perfusion (sometimes already compromised) and not cord compression at all. This distorted categorization causes confusion, false-alarm fatigue and difficulty in focusing on real pathological decelerations making CTG interpretation dysfunctional ultimately compromising patient safety. Obstetricians/midwives should demand reverting to the previous more scientific British categorization of decelerations based solely on time relationship to contractions as advocated by the pioneers like Hon and Caldeyro-Barcia, rather than accepting the current “post-truth” scenario. PMID:28270884

Uterine sarcoma vs adenocarcinoma: can MRI distinguish between them?

PubMed

Hernández Mateo, P; Méndez Fernández, R; Serrano Tamayo, E

2016-01-01

To analyze the MRI characteristics of uterine sarcomas (mainly carcinosarcomas) and to compare them with those of adenocarcinomas to define the findings that would be useful for the differential diagnosis. We retrospectively reviewed the MRI studies of 13 patients with histologically diagnosed uterine sarcoma. We analyzed tumor size, signal in T2-weighted, unenhanced and gadolinium-enhanced T1-weighted, and diffusion-weighted sequences. We compared the data obtained with those of another series of 30 consecutive cases of adenocarcinomas studied with MRI. The sarcomas (> 9cm in 77% of cases) were considerably larger than the adenocarcinomas (p<0.001). There were no differences in FIGO staging by MRI or surgery: both tumor types were diagnosed in early stages. The signal intensity in T2-weighted images differed significantly between the two tumor types: all the sarcomas were heterogeneous and predominantly hyperintense with respect to the myometrium in T2-weighted sequences (p<0.001). In postcontrast studies, all the sarcomas showed enhancement greater than or equal to the myometrium; this finding was significantly different from the adenocarcinomas (p<0.001). In diffusion-weighted sequences, we found no significant differences in ADC values in the areas with greatest restriction, but the ADC map was more heterogeneous in the sarcomas. Uterine sarcomas do not have specific characteristics on MRI, but some findings can indicate the diagnosis. In our study, we found significant differences between sarcomas and adenocarcinomas. Sarcomas were larger, had more hyperintense and heterogeneous signal intensity in T2-weighted sequences, and enhanced more than or at least as much as the myometrium. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Expression and clinical implication of Beclin1, HMGB1, p62, survivin, BRCA1 and ERCC1 in epithelial ovarian tumor tissues.

PubMed

Ju, L-L; Zhao, C Y; Ye, K-F; Yang, H; Zhang, J

2016-05-01

The aim of the present study is to investigate the differential expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 protein in epithelial ovarian cancer (EOC) and to evaluate the relationship between autophagy and platinum resistance of EOC patients during platinum-based chemotherapy with the protein expression. Expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 were detected with immunohistochemistry in 60 patients, including 39 with epithelial ovarian cancer (EOC), 13 benign epithelial ovarian tumor tissue (BET) and 8 borderline ovarian tumor tissue. Beclin, p62 and ERCC1 expression was significantly higher in the EOC than the BET (p<0.05). No statistical significance was detected with HMGB1 or survivin expression among BET, borderline tumor and EOC (p>0.05). BRCA1 expression was lower in EOC than BET (p<0.05). The expression of Beclin, p62 and survivin significantly correlated with FIGO stage (p<0.05), while the expression of HMGB1 correlated with pathological type. For platinum-sensitive EOC patients, positive expression of Beclin1 and BRCA1 was lower, and positive P62 expression was higher than in platinum-resistant patients (p<0.05). BRCA1 expression was negatively correlated with Beclin1 and p62 expression (p<0.05). Inhibition of expression of beclin1 may suppress autophagy to enhance the efficiency of platinum-sensitive ovarian cancer. HMGB1, survivin and p62 are implicated in the development of ovarian cancer. ERCC1 might be a potential predictive marker for neoadjuvant treatment in the early stage of ovarian cancer, and BRCA1, Beclin1 and p62 as a biomarker to predict platinum resistance and prognosis of epithelial ovarian cancer.

The Occurrence of Fetal Microchimeric Cells in Endometrial Tissues Is a Very Common Phenomenon in Benign Uterine Disorders, and the Lower Prevalence of Fetal Microchimerism Is Associated with Better Uterine Cancer Prognoses

PubMed Central

Kotlabova, Katerina; Pirkova, Petra; Libalova, Pavla; Vernerova, Zdenka; Svoboda, Bohuslav; Kucera, Eduard

2014-01-01

This is the first study carried out to describe the role of fetal microchimerism (FM) in the pathogenesis of uterine cancer. The prevalence and concentration of male fetal microchimeric cells (FMCs) were examined in endometrial tissues in relation to subtypes of uterine cancer, and the histological grade and stage of the tumor. FM occurrence was analyzed in relation to risk factors, including hypertension, obesity, type 2 diabetes, dyslipidemia, age at cancer diagnosis, and patient pregnancy history. The prevalence and concentration of FMCs were examined in endometrial tissues using real-time polymerase chain reaction, SRY and β-globin sequences as markers for male fetal FMCs and total DNA. The studied group involved 47 type 1 endometrial cancers, 28 type 2 endometrial cancers, and 41 benign uterine diseases. While the prevalence of FM was decreased only in type 1 endometrial cancer, compared with benign uterine disorders (38.3% vs.70.7%; odds ratio [OR]=0.257, 95% confidence interval [CI]: 0.105 to 0.628, p=0.003), FMC concentrations did not differ within examined groups. The lower FM prevalence was detected in low-grade (grade 1 and grade 2) endometrioid cancer (38.3% vs. 70.7%, OR=0.256, 95% CI: 0.105 to 0.627, p=0.003) and in FIGO 1 tumors (40.7% vs. 70.7%, OR=0.285, 95% CI: 0.120 to 0.675, p=0.004). No correlation between FM prevalence or FMC concentrations and risk factors was demonstrated. A lower prevalence of male FM seemed to be associated with better prognoses in uterine cancer based on tumor subtype, histological grade, and stage of the tumor. PMID:24283364

Serum concentrations of soluble (s)L- and (s)P-selectins in women with ovarian cancer.

PubMed

Majchrzak-Baczmańska, Dominika B; Głowacka, Ewa; Wilczyński, Miłosz; Malinowski, Andrzej

2018-03-01

The aim of the study was to compare serum concentration of soluble L- and P-selectins in women with ovarian cancer (OC) and healthy controls, and to investigate sL- and sP-selectin levels with regard to clinical and pathological parameters. Correlation analysis was used to measure the following: sL- and sP-selectin concentration and Ca125; sP-selectin and platelet concentrations; and sL-selectin and serum leukocyte levels in women with OC. The study included 29 patients with OC and 23 healthy controls. Serum concentrations of sL- and sP-selectins were measured in all subjects. Routine diagnostic tests: CBC and USG (both groups) and Ca125 (study group) were performed. Significantly higher serum concentrations of sL- and sP-selectins were found in the study group as compared to controls. Lower levels of serum sL-selectin were observed in women with poorly-differentiated OC (G3) and advanced stages of the disease (FIGO III, IV), but the results were statistically insignificant. No statistically significant relationship was detected between sP-selectin serum concentration in women with OC and tumour differentiation, histological type, and stage of the disease. No significant correlation was found between sL- and sP-selectins and Ca125 levels. A weak correlation was found between serum concentration of sP-selectin in women with OC and platelet count. No statistically significant correlation was observed between sL-selectin concentration and serum leukocyte levels in women with OC. The analysis of sL- and sP-selectin concentrations may be a useful tool in the diagnosis of OC. The levels of sL-selectin decrease with disease progression.

Sentinel lymph node biopsy in the management of early-stage cervical carcinoma.

PubMed

Diaz, John P; Gemignani, Mary L; Pandit-Taskar, Neeta; Park, Kay J; Murray, Melissa P; Chi, Dennis S; Sonoda, Yukio; Barakat, Richard R; Abu-Rustum, Nadeem R

2011-03-01

We aimed to determine the sentinel lymph node detection rates, accuracy in predicting the status of lymph node metastasis, and if pathologic ultrastaging improves the detection of micrometastases and isolated tumor cells at the time of primary surgery for cervical cancer. A prospective, non-randomized study of women with early-stage (FIGO stage IA1 with lymphovascular space involvement--IIA) cervical carcinoma was conducted from June 2003 to August 2009. All patients underwent an intraoperative intracervical blue dye injection. Patients who underwent a preoperative lymphoscintigraphy received a 99m Tc sulfur colloid injection in addition. All patients underwent sentinel lymph node (SLN) identification followed by a complete pelvic node and parametrial dissection. SLN were evaluated using our institutional protocol that included pathologic ultrastaging. SLN mapping was successful in 77 (95%) of 81 patients. A total of 316 SLN were identified, with a median of 3 SLN per patient (range, 0-10 SLN). The majority (85%) of SLN were located at three main sites: the external iliac (35%); internal iliac (30%); and obturator (20%). Positive lymph nodes (LN) were identified in 26 (32%) patients, including 21 patients with positive SLN. Fifteen of 21 patients (71%) had SLN metastasis detected on routine processing. SLN ultrastaging detected metastasis in an additional 6/21 patients (29%). Two patients had grossly positive LN at exploration, and mapping was abandoned. Three of 26 (12%) patients had successful SLN mapping; however, the SLN failed to identify the metastatic LN. Of these 3 false negative cases, 2 patients had a metastatic parametrial node as the only positive LN with multiple negative pelvic nodes including negative SLN. One patient with stage IA1 disease and lymphovascular invasion had unilateral SLN mapping and a metastatic common iliac LN identified on completion lymphadenectomy of the contralateral side that did not map. The 4 (5%) patients with unsuccessful mapping included 1 who had grossly positive nodes identified at the time of laparotomy; the remaining 3 occurred during each surgeon's initial SLN mapping learning phase. SLN mapping in early-stage cervical carcinoma yields high detection rates. Ultrastaging improves micrometastasis detection. Parametrectomy and side-specific lymphadenectomy (in cases of failed mapping) remain important components of the surgical management of selected cases. Copyright © 2010 Elsevier Inc. All rights reserved.

FHR patterns that become significant in connection with ST waveform changes and metabolic acidosis at birth.

PubMed

Rosén, Karl G; Norén, Håkan; Carlsson, Ann

2018-04-18

Recent developments have produced new CTG classification systems and the question is to what extent these may affect the model of FHR + ST interpretation? The two new systems (FIGO2015 and SSOG2017) classify FHR + ST events differently from the current CTG classification system used in the STAN interpretation algorithm (STAN2007). Identify the predominant FHR patterns in connection with ST events in cases of cord artery metabolic acidosis missed by the different CTG classification systems. Indicate to what extent STAN clinical guidelines could be modified enhancing the sensitivity. Provide a pathophysiological rationale. Forty-four cases with umbilical cord artery metabolic acidosis were retrieved from a European multicenter database. Significant FHR + ST events were evaluated post hoc in consensus by an expert panel. Eighteen cases were not identified as in need of intervention and regarded as negative in the sensitivity analysis. In 12 cases, ST changes occurred but the CTG was regarded as reassuring. Visual analysis of the FHR + ST tracings revealed specific FHR patterns: Conclusion: These findings indicate FHR + ST analysis may be undertaken regardless of CTG classification system provided there is a more physiologically oriented approach to FHR assessment in connection with an ST event.

Lymphadenectomy for the management of endometrial cancer

PubMed Central

May, Katie; Bryant, Andrew; Dickinson, Heather O; Kehoe, Sean; Morrison, Jo

2014-01-01

Background Endometrial carcinoma is the most common gynaecological cancer in western Europe and North America. Lymph node metastases can be found in approximately 10% of women who clinically have cancer confined to the womb prior to surgery and removal of all pelvic and para-aortic lymph nodes (lymphadenectomy) is widely advocated. Pelvic and para-aortic lymphadenectomy is part of the FIGO staging system for endometrial cancer. This recommendation is based on non-randomised controlled trials (RCTs) data that suggested improvement in survival following pelvic and para-aortic lymphadenectomy. However, treatment of pelvic lymph nodes may not confer a direct therapeutic benefit, other than allocating women to poorer prognosis groups. Furthermore, a systematic review and meta-analysis of RCTs of routine adjuvant radiotherapy to treat possible lymph node metastases in women with early-stage endometrial cancer, did not find a survival advantage. Surgical removal of pelvic and para-aortic lymph nodes has serious potential short and long-term sequelae and most women will not have positive lymph nodes. It is therefore important to establish the clinical value of a treatment with known morbidity. Objectives To evaluate the effectiveness and safety of lymphadenectomy for the management of endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009. Cochrane Gynaecological Cancer Review Group Trials Register, MEDLINE (1966 to June 2009), Embase (1966 to June 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria RCTs and quasi-RCTs that compared lymphadenectomy with no lymphadenectomy, in adult women diagnosed with endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received lymphadenectomy or no lymphadenectomy were pooled in random effects meta-analyses. Main results Two RCTs met the inclusion criteria; they randomised 1945 women, and reported HRs for survival, adjusted for prognostic factors, based on 1851 women. Meta-analysis indicated no significant difference in overall and recurrence-free survival between women who received lymphadenectomy and those who received no lymphadenectomy (pooled HR = 1.07, 95% CI: 0.81 to 1.43 and HR = 1.23, 95% CI: 0.96 to 1.58 for overall and recurrence-free survival respectively). We found no statistically significant difference in risk of direct surgical morbidity between women who received lymphadenectomy and those who received no lymphadenectomy. However, women who received lymphadenectomy had a significantly higher risk of surgically related systemic morbidity and lymphoedema/lymphocyst formation than those who had no lymphadenectomy (RR = 3.72, 95% CI: 1.04 to 13.27 and RR = 8.39, 95% CI: 4.06, 17.33 for risk of surgically related systemic morbidity and lymphoedema/lymphocyst formation respectively). Authors’ conclusions We found no evidence that lymphadenectomy decreases the risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. The evidence on serious adverse events suggests that women who receive lymphadenectomy are more likely to experience surgically related systemic morbidity or lymphoedema/lymphocyst formation. PMID:20091639

Interobserver agreement in CTG interpretation using the 2015 FIGO guidelines for intrapartum fetal monitoring.

PubMed

Rei, Mariana; Tavares, Sara; Pinto, Pedro; Machado, Ana P; Monteiro, Sofia; Costa, Antónia; Costa-Santos, Cristina; Bernardes, João; Ayres-De-Campos, Diogo

2016-10-01

Visual analysis of cardiotocographic (CTG) tracings has been shown to be prone to poor intra- and interobserver agreement when several interpretation guidelines are used, and this may have an important impact on the technology's performance. The aim of this study was to evaluate agreement in CTG interpretation using the new 2015 FIGO guidelines on intrapartum fetal monitoring. A pre-existing database of intrapartum CTG tracings was used to sequentially select 151 cases acquired with a fetal electrode, with duration exceeding 60minutes, and signal loss less than 15%. These tracings were presented to six clinicians, three with more than 5 years' experience in the labor ward, and three with 5 or less years' experience. Observers were asked to evaluate tracings independently, to assess basic CTG features: baseline, variability, accelerations, decelerations, sinusoidal pattern, tachysystole, and to classify each tracing as normal, suspicious or pathologic, according to the 2015 FIGO guidelines on intrapartum fetal monitoring. Agreement between observers was evaluated using the proportions of agreement (Pa), with 95% confidence intervals (95%CI). A good interobserver agreement was found in the evaluation of most CTG features, but not bradycardia, reduced variability, saltatory pattern, absence of accelerations and absence of decelerations. For baseline classification Pa was 0.85 [0.82-0.90], for variability 0.82 [0.78-0.85], for accelerations 0.72 [0.68-0.75], for tachysystole 0.77 [0.74-0.81], for decelerations 0.92 [0.90-0.95], for variable decelerations 0.62 [0.58-0.65], for late decelerations 0.63 [0.59-0.66], for repetitive decelerations 0.73 [0.69-0.78], and for prolonged decelerations 0.81 [0.77-0.85]. For overall CTG classification, Pa were 0.60 [0.56-0.64], for classification as normal 0.67 [0.61-0.72], for suspicious 0.54 [0.48-0.60] and for pathologic 0.59 [0.51-0.66]. No differences in agreement according to the level of expertise were observed, except in the identification of accelerations, where it was better in the more experienced group. A good interobserver agreement was found in evaluation of most CTG features and in overall tracing classification. Results were better than those reported in previous studies evaluating agreement in overall tracing classification. Observer experience did not appear to play a role in agreement. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cancer testis antigen OY-TES-1: analysis of protein expression in ovarian cancer with tissue microarrays.

PubMed

Fan, R; Huang, W; Luo, B; Zhang, Q M; Xiao, S W; Xie, X X

2015-01-01

Revised manuscript accepted for publication March 5, Objectives: The purpose of this study was to determine the potential of cancer testis antigen OY-TES-1 as a vaccine for ovarian cancer (OC). A tissue microarray (TMA) containing 107 samples from OC tissues and 48 samples from OC adjacent tissues was analyzed by immunohistochemistry with the OY-TES-1 polyclonal antibody. The correlation between OY-TES-1 and clinic pathological traits of OC was statistically analyzed. The expression of OY-TES-1 protein was found in 81% (87/107) of OC tissues and 56% (27/48) of OC adjacent tissues. The immunostaining intensity of OY-TES-1 in OC tissues was significantly higher than that in OC adjacent tissues tested (p = 0.040). OC adjacent tissues only demonstrated lower immunostaining intensity, whereas some of OC tissues presented higher immunostaining intensity and majority showed the heterogeneity of protein distribution. There was no statistically significant correlation found between OY-TES-1 expression and any other clinicopathological traits such as age, FIGO stage, pathological grade, and histological type. OY-TES-1 was expressed in OC tissues with a high proportion, and some of OC tissues presented OY-TES-1 expression in high level vs OC adjacent tissues. OY-TES-1 could be an attractive target for immunotherapy for OC in the future.

Implementation of image-guided brachytherapy (IGBT) for patients with uterine cervix cancer: a tumor volume kinetics approach

PubMed Central

Mendez, Lucas Castro; Stuart, Silvia Radwanski; Guimarães, Roger Guilherme Rodrigues; Ramos, Clarissa Cerchi Angotti; de Paula, Lucas Assad; de Sales, Camila Pessoa; Chen, André Tsin Chih; Blasbalg, Roberto; Baroni, Ronaldo Hueb

2016-01-01

Purpose To evaluate tumor shrinking kinetics in order to implement image-guided brachytherapy (IGBT) for the treatment of patients with cervix cancer. Material and methods This study has prospectively evaluated tumor shrinking kinetics of thirteen patients with uterine cervix cancer treated with combined chemoradiation. Four high dose rate brachytherapy fractions were delivered during the course of pelvic external beam radiation therapy (EBRT). Magnetic resonance imaging (MRI) exams were acquired at diagnosis (D), first (B1), and third (B3) brachytherapy fractions. Target volumes (GTV and HR-CTV) were calculated by both the ellipsoid formula (VE) and MRI contouring (VC), which were defined by a consensus between at least two radiation oncologists and a pelvic expert radiologist. Results Most enrolled patients had squamous cell carcinoma and FIGO stage IIB disease, and initiated brachytherapy after the third week of pelvic external beam radiation. Gross tumor volume volume reduction from diagnostic MRI to B1 represented 61.9% and 75.2% of the initial volume, when measured by VE and VC, respectively. Only a modest volume reduction (15-20%) was observed from B1 to B3. Conclusions The most expressive tumor shrinking occurred in the first three weeks of oncological treatment and was in accordance with gynecological examination. These findings may help in IGBT implementation. PMID:27648083

[Occurrence of radiation-induced injury in vagina after radical radiotherapy of cervical cancer and its affecting factors].

PubMed

Zhang, K S; Liu, Z; Wang, T; Wang, J; Su, J; Shi, F; Wang, R H; Yuan, W; Li, Y

2018-04-25

Objective: To investigate the occurrence and degree of radiation-induced injury in vagina after radical radiotherapy of cervical cancer. Methods: A total of 282 cases of patients with cervical cancer were collected from November 2016 to September 2017. All of the above patients underwent radical radiotherapy from 2008 to 2017 in the First Affiliated Hospital of Xi ' an Jiaotong University. The patients' International Federation of Gynecology and Obstetrics (FIGO) staging (2009) , brachytherapy dose, whether receive synchronous chemotherapy or not, age and body mass index (BMI) for the occurrence and severity of vaginal radiation injury at different time periods were analyzed by cross-sectional survey method. The single factor would be analyzed by the method of Chi-square test and the multiple factors would be analyzed by logistic regression method to checkout. Results: Of the 282 patients, the incidence of radiation-injury in vaginal was 84.4% (238/282) , with the incidence rate of degree Ⅰ,Ⅱ and Ⅲ radiation injury were respectively 50.7% (143/282), 29.8% (84/282) and 3.9% (11/282; χ(2)=153.375, P< 0.05) , and there was no degree Ⅳ. Until the end of the follow-up time, the incidence of radiation-induced injury in vaginal after completing the treatment within 1 year, 1-2 years,>2-<5 years and ≥5 years were respectively 80.0% (24/30) , 87.2% (102/117) , 88.2% (60/68) and 77.6% (52/67; χ(2)=4.231, P= 0.238) . There were 30 cases be followed within 1 year after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ of radiation injury in vagina was 60.0% (18/30) , 20.0% (6/30) and 0, respectively (χ(2)=28.636, P< 0.05). There were 117 cases be followed between 1-2 years after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ vaginal radiation-induced injury were 54.7% (64/117) , 29.9% (35/117) and 2.6% (3/117) , respectively (χ(2)=77.198, P< 0.05) . There were 68 cases be followed between >2-<5 years after treatment, the incidence rate of degree Ⅰ,Ⅱ and Ⅲ vaginal radiation-induced injury were 51.5% (35/68) ,33.8% (23/68) and 2.9% (2/68) , respectively (χ(2)=39.525, P< 0.05) . There were 67 cases be followed ≥5 years after treatment, the incidence rate of degree Ⅰ,Ⅱ and Ⅲ vaginal radiation injury were 38.8% (26/67) , 29.9% (20/67) and 9.0% (6/67) , respectively (χ(2)=16.395, P< 0.05) . The single-factor analysis result indicated that the brachytherapy dose had an obvious effect on vaginal radiation-induced injury (χ(2)=5.344, P= 0.021) ; however, other factors, such as age, BMI, FIGO stages and synchronous chemotherapy, had no obvious effect on vaginal radiation-induced injury (all P> 0.05) . The multifactor analysis indicated that the brachytherapy dose was an independent factor affecting the occurrence of vaginal radiation-induced injury ( P= 0.043) . Conclusion: After the radical radiotherapy of cervical cancer, the vaginal radiation-induced injury is associated with the dose of brachytherapy.

[Clinicopathological characteristics of hereditary ovarian cancer syndrome].

PubMed

Zhong, Yan; Sheng, Xiu-gui; Ma, Zhi-fang; Ma, Yue-bing; Liu, Nai-fu; Chen, Yue-ting; Gao, Rong; Wang, Ying-ying; Sun, Li

2009-09-01

To explore the clinicopathological characteristics of hereditary ovarian cancer syndrome (HOCS). From Jan. 2000 to Jan. 2007, among 580 cases of primary ovarian cancer, 42 cases (hereditary group), who had a positive family history of ovarian cancer and met the diagnostic criteria of HOCS, were analyzed retrospectively. One hundred cases without a family history of ovarian cancer were enrolled randomizely as control group (sporadic group). The incidence of HOCS was 7.2% (42/580). Forty-two cases associated tumors affected at least 2 successive generations in 31 families and affected 1 generation in 8 families. Eighty-seven percent (27/31) was from maternal lineage, while 13% (4/31) from paternal lineage. Earlier age of onset was significantly difference between two groups [(49 +/- 10) years vs. (55 +/- 10) years, P < 0.05]. There were 90% belong to serous adenocarcinoma in the hereditary group, while 84% in the sporadic group. There was statistical difference in the proportion of mucinous adenocarcinoma (0 vs. 11%, P < 0.05). The most common clinical manifestations were abdominal distention and anorexia (64% vs. 70%, P > 0.05), International Federational of Gynecology Obstetrics (FIGO) stage III (62% vs. 63%, P > 0.05) between two groups. Fourteen cases (33%,14/42) were previously untreated in the hereditary group, while 40 cases (40%, 40/100) in the sporadic group. There were 15 cases (36%, 15/42) underwent secondary surgery and 15 cases (36%, 15/42) underwent third surgery or more in hereditary group, while 50 cases (50%,50/100) and 27 cases (27%, 27/100) in the sporadic group. The mean number of chemotherapy cycles received in two groups was 13.3 and 11.8 (P > 0.05). The 3-year and 5-year survival rate in hereditary group were 73.6% and 54.9% respectively, compared with 47.4% and 21.2% (P < 0.05) in sporadic group. Hereditary ovarian cancer mostly from maternal lineage are featuring in early age of onset, serous adenocarcinoma, advanced stage (stage III), and better prognosis after the comprehensive treated by cytoreductive surgery plus with chemotherapy.

Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma.

PubMed

Lacava, J A; Leone, B A; Machiavelli, M; Romero, A O; Perez, J E; Elem, Y L; Ferreyra, R; Focaccia, G; Suttora, G; Salvadori, M A; Cuevas, M A; Acuña, L R; Acuña, J R; Langhi, M; Amato, S; Castaldi, J; Arroyo, A; Vallejo, C T

1997-02-01

To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected. VNB is an active drug against ACC with moderate toxicity. Its activity is among the highest reported for single agents. Further evaluation in association with other agents is clearly justified.

Sentinel lymph node detection in early stage cervical cancer: a prospective study comparing preoperative lymphoscintigraphy, intraoperative gamma probe, and blue dye.

PubMed

Kara, P Pelin; Ayhan, Ali; Caner, Biray; Gültekin, Murat; Ugur, Omer; Bozkurt, M Fani; Usubutun, Alp

2008-07-01

The objective of this prospective study was to determine the feasibility of sentinel lymph node (SLN) detection in patients with cervical cancer using lymphoscintigraphy (LS), gamma probe, and blue dye. A total of 32 patients with early stage cervical cancer (FIGO IA2-IIA) who were treated with total abdominal hysterectomy and bilateral pelvic and paraortic lymphadenectomy underwent SLN biopsy. LS was performed on all the patients following the injection of 74 MBq technetium-99m-nanocolloid pericervically. The first appearing persistent focal accumulation on either dynamic or static images of LS was considered to be an SLN. Blue dye was injected just prior to surgical incision in 16 patients (50%) at the same locations as the radioactive isotope injection. During the operation, blue-stained node(s) were excised as SLNs. For gamma probe, a lymph node was accepted as an SLN, if its ex vivo radioactive counts were at least 10-fold above background radioactivity. SLNs, which were negative by routine hematoxylin and eosin (H&E) examination, were histopathologically reevaluated for the presence of micrometastases by step sectioning and immunohistochemical staining with pancytokeratin. At least one SLN was identified for each patient by gamma probe. Intraoperative gamma probe was the most sensitive method with a technical success rate of SLN detection of 100% (32/32), followed by LS 87.5% (28/32) and blue dye 68.8% (11/16), respectively. The average number of SLNs per patient detected by gamma probe was 2.09 (range 1-5). The localizations of the SLNs were external iliac 47.8%, obturatory 32.8%, common iliac 9%, paraaortic 4.4%, and paracervical 6%. Micrometastases, not detected by routine H&E were found by immunohistochemistry in one patient. On the basis of the histopathological analysis, the negative predictive value for predicting metastases was 100%, and there were no false-negative results. Preoperative LS with radiocolloids, intraoperative lymphatic mapping with blue dye and gamma probe are all feasible methods comparable with each other for SLN detection in early stage cervical cancer patients, but gamma probe is the most useful method in terms of technical success.

Endometrioid Adenocarcinoma Arising in a Paratubal Cyst: A Case Report and Review of the Literature.

PubMed

Chang, Catherine; Matsuo, Koji; Mhawech-Fauceglia, Paulette

2017-03-01

A 56-year-old G3P3 postmenopausal woman presented with a 5 month history of abnormal uterine bleeding and pelvic pain. A computed tomographic scan revealed a 5 cm right adnexal cystic mass in addition to a thickened, heterogenous endometrium and leiomyomatous uterus. A total laparascopic hysterectomy and bilateral salpingo-oophorectomy with omental and peritoneal biopsy were performed. Gross examination revealed a 12 week size uterus with small fibroids, normal bilateral atrophic ovaries, and a right paratubal cyst. A 4 cm vegetating mass was found in the right side of the uterine wall. Microscopically, the uterine mass was diagnosed as an endometrioid adenocarcinoma (EAC) FIGO 1 with 70% of myometrial invasion. The remaining endometrium showed a complex atypical hyperplasia. In addition, a 5 cm paratubal cystic mass was found that was separate from the uterus and the right adnexa. The cyst content was a chocolate brown fluid and the cyst wall was smooth with a single solid mass of 2 cm in size. The diagnosis of EAC, FIGO 1 was given. The remaining cyst lining showed endometriotic cyst and foci of endometriosis in the cyst wall. There was no lymphovascular invasion. The entire fallopian tube and ovaries were submitted and they were free of tumor. The patient was diagnosed with primary EAC of the paratubal cyst in addition to EAC of the uterine corpus (pT1b). A close follow-up was recommended. Because of our limited knowledge of carcinomas arising in the paratubal cyst, we will review the literature and discuss their clinical aspects, management, and behavior.

Hormone replacement therapy for women previously treated for endometrial cancer.

PubMed

Edey, Katharine A; Rundle, Stuart; Hickey, Martha

2018-05-15

Endometrial cancer is the sixth most common cancer in women worldwide and most commonly occurs after the menopause (75%) (globocan.iarc.fr). About 319,000 new cases were diagnosed worldwide in 2012. Endometrial cancer is commonly considered as a potentially 'curable cancer,' as approximately 75% of cases are diagnosed before disease has spread outside the uterus (FIGO (International Federation of Gynecology and Obstetrics) stage I). The overall five-year survival for all stages is about 86%, and, if the cancer is confined to the uterus, the five-year survival rate may increase to 97%. The majority of women diagnosed with endometrial cancer have early-stage disease, leading to a good prognosis after hysterectomy and removal of the ovaries (oophorectomy), with or without radiotherapy. However, women may have early physiological and psychological postmenopausal changes, either pre-existing or as a result of oophorectomy, depending on age and menopausal status at the time of diagnosis. Lack of oestrogen can cause hot flushes, night sweats, genital tract atrophy and longer-term adverse effects, such as osteoporosis and cardiovascular disease. These changes may be temporarily managed by using oestrogens, in the form of hormone replacement therapy (HRT). However, there is a theoretical risk of promoting residual tumour cell growth and increasing cancer recurrence. Therefore, this is a potential survival disadvantage in a woman who has a potentially curable cancer. In premenopausal women with endometrial cancer, treatment induces early menopause and this may adversely affect overall survival. Additionally, most women with early-stage disease will be cured of their cancer, making longer-term quality of life (QoL) issues more pertinent. Following bilateral oophorectomy, premenopausal women may develop significant and debilitating menopausal symptoms, so there is a need for information about the risk and benefits of taking HRT, enabling women to make an informed decision, weighing the advantages and disadvantages of using HRT for their individual circumstances. To assess the risks and benefits of HRT (oestrogen alone or oestrogen with progestogen) for women previously treated for endometrial cancer. We searched the Cochrane Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to April, week 4, 2017) and Embase (1980 to 2017, week 18). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles. We included randomised controlled trials (RCTs), in all languages, that examined the efficacy of symptom relief and the safety of using HRT in women treated for endometrial cancer, where safety in this situation was considered as not increasing the risk of recurrence of endometrial cancer above that of women not taking HRT. Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We used standard methodological procedures expected by Cochrane. We identified 2190 unique records, evaluated the full text of seven studies and included one study with 1236 participants. This study reported tumour recurrence in 2.3% of women in the oestrogen arm versus 1.9% of women receiving placebo (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.54 to 2.50; very low-certainty evidence). The study reported one woman in the HRT arm (0.16%) and three women in the placebo arm (0.49%) who developed breast cancer (new malignancy) during follow-up (RR 0.80, 95% CI 0.32 to 2.01; 1236 participants, 1 study; very low-certainty evidence). The study did not report on symptom relief, overall survival or progression-free survival for HRT versus placebo. However, they did report the percentage of women alive with no evidence of disease (94.3% in the HRT group and 95.6% in the placebo group) and the percentage of women alive irrespective of disease progression (95.8% in the HRT group and 96.9% in the placebo group) at the end of the 36 months' follow-up. The study did not report time to recurrence and it was underpowered due to closing early. The authors closed it as a result of the publication of the Women's Health Initiative (WHI) study, which, at that time, suggested that risks of exogenous hormone therapy outweighed benefits and had an impact on study recruitment. No assessment of efficacy was reported. Currently, there is insufficient high-quality evidence to inform women considering HRT after treatment for endometrial cancer. The available evidence (both the single RCT and non-randomised evidence) does not suggest significant harm, if HRT is used after surgical treatment for early-stage endometrial cancer. There is no information available regarding use of HRT in higher-stage endometrial cancer (FIGO stage II and above). The use of HRT after endometrial cancer treatment should be individualised, taking account of the woman's symptoms and preferences, and the uncertainty of evidence for and against HRT use.

Predictive and Prognostic Factors in Ovarian and Uterine Carcinosarcomas

PubMed Central

Cicin, İrfan; Özatlı, Tahsin; Türkmen, Esma; Özturk, Türkan; Özçelik, Melike; Çabuk, Devrim; Gökdurnalı, Ayşe; Balvan, Özlem; Yıldız, Yaşar; Şeker, Metin; Özdemir, Nuriye; Yapar, Burcu; Tanrıverdi, Özgür; Günaydin, Yusuf; Menekşe, Serkan; Öksüzoğlu, Berna; Aksoy, Asude; Erdogan, Bülent; Bekir Hacıoglu, M.; Arpaci, Erkan; Sevinç, Alper

2016-01-01

Background: Prognostic factors and the standard treatment approach for gynaecological carcinosarcomas have not yet been clearly defined. Although carcinosarcomas are more aggressive than pure epithelial tumours, they are treated similarly. Serous/clear cell and endometrioid components may be predictive factors for the efficacy of adjuvant chemotherapy (CT) or radiotherapy (RT) or RT in patients with uterine and ovarian carcinosarcomas. Heterologous carcinosarcomas may benefit more from adjuvant CT. Aims: We aimed to define the prognostic and predictive factors associated with treatment options in ovarian (OCS) and uterine carcinosarcoma (UCS). Study Design: Retrospective cross-sectional study Methods: We retrospectively reviewed the medical records of patients with ovarian and uterine carcinosarcoma from 2000 to 2013, and 127 women were included in this study (24 ovarian and 103 uterine). Patients admitted to seventeen oncology centres in Turkey between 2000 and December 2013 with a histologically proven diagnosis of uterine carcinosarcoma with FIGO 2009 stage I–III and patients with sufficient data obtained from well-kept medical records were included in this study. Stage IV tumours were excluded. The patient records were retrospectively reviewed. Data from 104 patients were evaluated for this study. Results: Age (≥70 years) was a poor prognostic factor for UCS (p=0.036). Pelvic±para aortic lymph node dissection did not affect overall survival (OS) (p=0.35). Macroscopic residual disease was related with OS (p<0.01). The median OS was significantly longer in stage I–II patients than stage III patients (p=0.03). Adjuvant treatment improved OS (p=0.013). Adjuvant radiotherapy tended to increase the median OS (p=0.075). However, this tendency was observed in UCS (p=0.08) rather than OCS (p=0.6).Adjuvant chemotherapy had no effect on OS (p=0.15).Adjuvant radiotherapy significantly prolonged the median OS in patients with endometrioid component (p=0.034). A serous/clear cell component was a negative prognostic factor (p=0.035). Patients with serous/clear cell histology for whom adjuvant chemotherapy was applied had significantly longer OS (p=0.019), and there was no beneficial effect of adjuvant radiotherapy (p=0.4). Adjuvant chemotherapy was effective in heterologous tumours (p=0.026). In multivariate analysis, the stage and chemotherapy were prognostic factors for all patients. Age was an independent prognostic factor for UCS. However, serous/clear cell histology and radiotherapy tended to be significant prognostic factors. Conclusion: The primary location, the histological type of sarcomatous and the epithelial component may be predictive factors for the efficacy of chemotherapy or radiotherapy in UCS and OCS. PMID:27761279

Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients

PubMed Central

2012-01-01

Background Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15–3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. Methods Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15–3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. Results Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15–3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease. Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. Conclusions This study found significantly elevated Mucin-1 serum concentrations in ovarian carcinoma patients as compared to those women suffering from benign ovarian diseases. However, it needs to be noted that Mucin-1 concentrations in carcinoma patients showed a rather high variability. Results from immunohistochemistry indicate that Mucin-1 has a prognostic relevance in ovarian carcinomas when evaluating the expression by VU4H5 antibody. PMID:23241107

Angiogenesis and lymphangiogenesis as prognostic factors after therapy in patients with cervical cancer

PubMed Central

Makarewicz, Roman; Kopczyńska, Ewa; Marszałek, Andrzej; Goralewska, Alina; Kardymowicz, Hanna

2012-01-01

Aim of the study This retrospective study attempts to evaluate the influence of serum vascular endothelial growth factor C (VEGF-C), microvessel density (MVD) and lymphatic vessel density (LMVD) on the result of tumour treatment in women with cervical cancer. Material and methods The research was carried out in a group of 58 patients scheduled for brachytherapy for cervical cancer. All women were patients of the Department and University Hospital of Oncology and Brachytherapy, Collegium Medicum in Bydgoszcz of Nicolaus Copernicus University in Toruń. VEGF-C was determined by means of a quantitative sandwich enzyme immunoassay using a human antibody VEGF-C ELISA produced by Bender MedSystem, enzyme-linked immunosorbent detecting the activity of human VEGF-C in body fluids. The measure for the intensity of angiogenesis and lymphangiogenesis in immunohistochemical reactions is the number of blood vessels within the tumour. Statistical analysis was done using Statistica 6.0 software (StatSoft, Inc. 2001). The Cox proportional hazards model was used for univariate and multivariate analyses. Univariate analysis of overall survival was performed as outlined by Kaplan and Meier. In all statistical analyses p < 0.05 (marked red) was taken as significant. Results In 51 patients who showed up for follow-up examination, the influence of the factors of angiogenesis, lymphangiogenesis, patients’ age and the level of haemoglobin at the end of treatment were assessed. Selected variables, such as patients’ age, lymph vessel density (LMVD), microvessel density (MVD) and the level of haemoglobin (Hb) before treatment were analysed by means of Cox logical regression as potential prognostic factors for lymph node invasion. The observed differences were statistically significant for haemoglobin level before treatment and the platelet number after treatment. The study revealed the following prognostic factors: lymph node status, FIGO stage, and kind of treatment. No statistically significant influence of angiogenic and lymphangiogenic factors on the prognosis was found. Conclusion Angiogenic and lymphangiogenic factors have no value in predicting response to radiotherapy in cervical cancer patients. PMID:23788848

Treosulfan in the Treatment of Advanced Ovarian Cancer - Results of a German Multicenter Non-interventional Study.

PubMed

Chekerov, Radoslav; Kaltenecker, Gabriele; Reichert, Dietmar; Göhler, Thomas; Klare, Peter; Oskay-Özcelik, Gülten; Sauer, Uwe; Wischnik, Arthur; Vehling-Kaiser, Ursula; Becker, Martin; Hutzschenreuter, Ulrich; Ammon, Andreas; Heidrich-Lorsbach, Elke; Sehouli, Jalid

2015-12-01

Data on routine systemic treatment of patients with ovarian cancer are currently available only to a limited degree. The alkylating agent treosulfan is approved in oral (p.o.) and intravenous (i.v.) form for the treatment of ovarian carcinoma. The present non-interventional study analyzed the clinical use of treosulfan in Germany, evaluating the mode of application, toxicity, and response and survival rate. Two hundred and forty-eight ovarian cancer patients in 57 Centers, who received treosulfan mainly either i.v. (5,000-8,000 mg/m(2) d1, q21d or q28d) or p.o. (400-600 mg/m(2) d1-14 or 21, q28d) for at least one therapy cycle were evaluable and were included in the study. With a median age of 70 years (range=36-92 years), predominantly elderly patients received treosulfan treatment. Most participants presented serous histology (131, 52.8%) and advanced-stage FIGO III (122, 49%) or IV (55, 22%) disease. Median ECOG status was 1 (range=0-2), whereas cardiac co-morbidity was common (31%). Treosulfan was usually administered as second- (26%), third- (21%) or fourth-line (17%) therapy. Two hundred and one patients received i.v. and 47 p.o. The most common reason for dose modifications was due to hematological toxicity (46%). The main reason for a therapy discontinuation was progressive disease (38.5%). Response was observed in 25.8% of participants, disease stabilization in 28.6 % and progress in 45.6%. The median progression-free and overall survival was 196 and 405 days, respectively. In predominantly elderly and heavily pre-treated patients with recurrent ovarian cancer, treosulfan featured a clinical relevant efficacy and well-manageable, mostly hematological, toxicity, which resulted in a positive therapeutic index. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients successfully treated with methotrexate alone.

PubMed

Couder, Florence; Massardier, Jérôme; You, Benoît; Abbas, Fatima; Hajri, Touria; Lotz, Jean-Pierre; Schott, Anne-Marie; Golfier, François

2016-07-01

Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasia patients. This retrospective study analyzes the predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients whose hormone chorionic gonadotropin (hCG) normalized with methotrexate alone. Between 1999 and 2014, 993 patients with gestational trophoblastic neoplasia were identified in the French Trophoblastic Disease Reference Center database, of which 465 were low-risk patients whose hCG normalized with methotrexate alone. Using univariate and multivariate analysis we identified significant predictive factors for relapse after methotrexate. The Kaplan-Meier method was used to plot the outcome of patients. The 5-year recurrence rate of low-risk gestational trophoblastic neoplasia patients whose hCG normalized with methotrexate alone was 5.7% (confidence interval [IC], 3.86-8.46). Univariate analysis identified an antecedent pregnancy resulting in a delivery (HR = 5.96; 95% CI, 1.40-25.4, P = .016), a number of methotrexate courses superior to 5 courses (5-8 courses vs 1-4: HR = 6.19; 95% CI, 1.43-26.8, P = .015; 9 courses and more vs 1-4: HR = 6.80; 95% CI, 1.32-35.1, P = .022), and hCG normalization delay centered to the mean as predictive factors of recurrence (HR = 1.27; 95% CI, 1.09-1.49, P = .003). Multivariate analysis confirmed the type of antecedent pregnancy and the number of methotrexate courses as independent predictive factors of recurrence. A low-risk gestational trophoblastic neoplasia arising after a normal delivery had an 8.66 times higher relapse risk than that of a postmole gestational trophoblastic neoplasia (95% CI, 1.98-37.9], P = .0042). A patient who received 5-8 courses of methotrexate had a 6.7 times higher relapse risk than a patient who received 1-4 courses (95% CI, 1.54-29.2, P = .011). A patient who received 9 courses or more had an 8.1 times higher relapse risk than a patient who received 1-4 courses of methotrexate (95% CI, 1.54-42.6, P = .014). Low-risk gestational trophoblastic neoplasia following a delivery and patients who need more than 4 courses of methotrexate to normalization are at a higher risk of relapse than other low-risk patients. Allotting a higher score to the "antecedent pregnancy" FIGO item should be considered for postdelivery gestational trophoblastic neoplasia. Further analysis of the need for consolidation courses is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

[Alterations of c-Myc and c-erbB-2 genes in ovarian tumours].

PubMed

Pastor, Tibor; Popović, Branka; Gvozdenović, Ana; Boro, Aleksandar; Petrović, Bojana; Novaković, Ivana; Puzović, Dragana; Luković, Ljiljana; Milasin, Jelena

2009-01-01

According to clinical and epidemiological studies, ovarian cancer ranks fifth in cancer deaths among women. The causes of ovarian cancer remain largely unknown but various factors may increase the risk of developing it, such as age, family history of cancer, childbearing status etc. This cancer results from a succession of genetic alterations involving oncogenes and tumour suppressor genes, which have a critical role in normal cell growth regulation. Mutations and/or overexpression of three oncogenes, c-erbB-2, c-Myc and K-ras, and of the tumour suppressor gene p53, have been frequently observed in a sporadic ovarian cancer. The aim of the present study was to analyse c-Myc and c-erbB-2 oncogene alterations, specifically amplification, as one of main mechanisms of their activation in ovarian cancers and to establish a possible association with the pathogenic process. DNA was isolated from 15 samples of malignant and 5 benign ovarian tumours, using proteinase K digestion, followed by phenol-chloroform isoamyl extraction and ethanol precipitation. C-Myc and c-erbB-2 amplification were detected by differential PCR. The level of gene copy increase was measured using the Scion image software. The amplification of both c-Myc and c-erbB-2 was detected in 26.7% of ovarian epithelial carcinoma specimens. Only one tumour specimen concomitantly showed increased gene copy number for both studied genes. Interestingly, besides amplification, gene deletion was also detected (26.7% for c-erbB-2). Most of the ovarian carcinomas with alterations in c-Myc and c-erbB-2 belonged to advanced FIGO stages. The amplification of c-Myc and c-erbB-2 oncogenes in ovarian epithelial carcinomas is most probably a late event in the pathogenesis conferring these tumours a more aggressive biological behaviour. Similarly, gene deletions point to genomic instability in epithelial carcinomas in higher clinical stages as the result of clonal evolution and selection.

Preoperative CA125 and fibrinogen in patients with endometrial cancer: a risk model for predicting lymphovascular space invasion

PubMed Central

2017-01-01

Objective The aim of this study was to build a model to predict the risk of lymphovascular space invasion (LVSI) in women with endometrial cancer (EC). Methods From December 2010 to June 2013, 211 patients with EC undergoing surgery at Shanghai First Maternity and Infant Hospital were enrolled in this retrospective study. Those patients were divided into a positive LVSI group and a negative LVSI group. The clinical and pathological characteristics were compared between the two groups; logistic regression was used to explore risk factors associated with LVSI occurrence. The threshold values of significant factors were calculated to build a risk model and predict LVSI. Results There were 190 patients who were negative for LVSI and 21 patients were positive for LVSI out of 211 patients with EC. It was found that tumor grade, depth of myometrial invasion, number of pelvic lymph nodes, and International Federation of Gynecology and Obstetrics (FIGO) stage (p<0.05) were associated with LVSI occurrence. However, cervical involvement and age (p>0.05) were not associated with LVSI. Receiver operating characteristic (ROC) curves revealed that the threshold values of the following factors were correlated with positive LVSI: 28.1 U/mL of CA19-9, 21.2 U/mL of CA125, 2.58 mg/dL of fibrinogen (Fn), 1.84 U/mL of carcinoembryonic antigen (CEA) and (6.35×109)/L of white blood cell (WBC). Logistic regression analysis indicated that CA125 ≥21.2 (p=0.032) and Fn ≥2.58 mg/dL (p=0.014) were significantly associated with LVSI. Conclusion Positive LVSI could be predicted by CA125 ≥21.2 U/mL and Fn ≥2.58 mg/dL in women with EC. It could help gynecologists better adapt surgical staging and adjuvant therapies. PMID:27894164

Tumor-free distance from outermost layer of cervix is of prognostic value in surgically treated cervical cancer patients: a multicenter study.

PubMed

Saatli, Bahadir; Olgan, Safak; Gorken, Iknur B; Uslu, Turhan; Saygili, Ugur; Dicle, Nilgun; Cingillioglu, Basak; Gumurdulu, Derya; Guzel, Ahmet Baris; Koyuncuoglu, Meral

2014-06-01

This study aimed at determining if tumor-free distance (TFD) from outermost layer of cervix predicts surgicopathologic factors and outcome in surgically treated cervical cancer patients. One hundred sixteen surgically treated cervical squamous cell carcinomas between 1991 and 2010 with FIGO stage IB/2A were identified and re-evaluated histologically regarding the TFD. TFD was defined as the distance between outermost layer of cervix and deepest cervical stromal invasion. Depth of invasion (DOI) and TFD were expressed as continuous variables and compared with traditional surgicopathologic variables and survival to determine their prognostic significance. The mean DOI was 10.3 mm and the mean TFD was 4.2 mm. The most common stage was IB1 (60 patients, 51.7 %). The mean number of removed pelvic lymph nodes was 32.2 (median 30; range 8-78). Positive pelvic lymph nodes were found in 27 (23 %) of the patients. Sixty-eight patients had lymphovascular space involvement (LVSI). Sixty-eight patients (59 %) received postoperative radiotherapy where the following items were present: tumor diameter >4 cm, positive lymph nodes, LVSI and positive surgical margins. With the median follow-up of 53 months (3-219 months); 14 patients had local and 13 patients had distant metastases (5 of the patients had both at the time of recurrence). With logistic regression analysis, TFD was a predictor of pelvic lymph involvement (p = 0.028) and LVSI (p = 0.008) while DOI was a predictor of LVSI (p = 0.044). In Cox regression analysis, increased TFD was associated with improved disease-free survival (DFS) (p = 0.007). DFS curves (for TFD cut off value 2.5 mm) according to Kaplan-Meier were found to be statistically significant (log rank test = 0.002). The results indicate that TFD is predictive of pelvic lymph node involvement, LVSI and patient outcome in surgically treated cervical cancer patients. However, prospective measurement of TFD is still necessary to determine its value in clinical practice.

[Third National Ovarian Consensus. 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM"].

PubMed

Gallardo-Rincón, Dolores; Cantú-de-León, David; Alanís-López, Patricia; Alvarez-Avitia, Miguel Angel; Bañuelos-Flores, Joel; Herbert-Núñez, Guillermo Sidney; Oñate-Ocaña, Luis Fernando; Pérez-Montiel, María Delia; Rodríguez-Trejo, Amelia; Ruvalcaba-Limón, Eva; Serrano-Olvera, Alberto; Ortega-Rojo, Andrea; Cortés-Esteban, Patricia; Erazo-Valle, Aura; Gerson-Cwilich, Raquel; De-la-Garza-Salazar, Jaime; Green-Renner, Dan; León-Rodríguez, Eucario; Morales-Vásquez, Flavia; Poveda-Velasco, Andrés; Aguilar-Ponce, José Luis; Alva-López, Luis Felipe; Alvarado-Aguilar, Salvador; Alvarado-Cabrero, Isabel; Aquino-Mendoza, Cinthia Alejandra; Aranda-Flores, Carlos Eduardo; Bandera-Delgado, Artfy; Barragán-Curiel, Eduardo; Barrón-Rodríguez, Patricia; Brom-Valladares, Rocío; Cabrera-Galeana, Paula Anel; Calderillo-Ruiz, Germán; Camacho-Gutiérrez, Salvador; Capdeville-García, Daniel; Cárdenas-Sánchez, Jesús; Carlón-Zárate, Elisa; Carrillo-Garibaldi, Oscar; Castorena-Roji, Gerardo; Cervantes-Sánchez, Guadalupe; Coronel-Martínez, Jaime Alberto; Chanona-Vilchis, José Gregorio; Díaz-Hernández, Verónica; Escudero-de-los Ríos, Pedro; Garibay-Cerdenares, Olga; Gómez-García, Eva; Herrera-Montalvo, Luis Alonso; Hinojosa-García, Luz María; Isla-Ortiz, David; Jiménez-López, Josefina; Lavín-Lozano, Arturo Javier; Limón-Rodriguez, Jesús Alberto; López-Basave, Horacio Noé; López-García, Sergio César; Maffuz-Aziz, Antonio; Martínez-Cedillo, Jorge; Martínez-López, Dulce María; Medina-Castro, Juan Manuel; Melo-Martínez, Carlos; Méndez-Herrera, Carmen; Montalvo-Esquivel, Gonzalo; Morales-Palomares, Miguel Angel; Morán-Mendoza, Andrés; Morgan-Villela, Gilberto; Mota-García, Aída; Muñoz-González, David Eduardo; Ochoa-Carrillo, Francisco J; Pérez-Amador, Maricruz; Recinos-Money, Edgar; Rivera-Rivera, Samuel; Robles Flores, Juan U; Rojas-Castillo, Edith; Rojas-Marín, Carlos; Salas-Gonzáles, Efraín; Sámano-Nateras, Liliana; Santibañez-Andrade, Miguel; Santillán-Gómez, Antonio; Silva-García, Araceli; Silva, Juan Alejandro; Solorza-Luna, Gilberto; Tabarez-Ortiz, Adán Raúl; Talamás-Rohana, Patricia; Tirado-Gómez, Laura Leticia; Torres-Lobatón, Alfonso; Quijano-Castro, Félix

2011-01-01

Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide. Most of cases it is of epithelial origin. At the present time there is not a standardized screening method, which makes difficult the early diagnosis. The 5-year survival is 90% for early stages, however most cases present at advanced stages, which have a 5-year survival of only 5-20%. GICOM collaborative group, under the auspice of different institutions, have made the following consensus in order to make recommendations for the diagnosis and management regarding to this neoplasia. The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of two days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. No screening method is recommended at the time for the detection of early lesions of ovarian cancer in general population. Staging is surgical, according to FIGO. In regards to the pre-surgery evaluation of the patient, it is recommended to perform chest radiography and CT scan of abdomen and pelvis with IV contrast. According to the histopathology of the tumor, in order to consider it as borderline, the minimum percentage of proliferative component must be 10% of tumor's surface. The recommended standardized treatment includes primary surgery for diagnosis, staging and cytoreduction, followed by adjuvant chemotherapy Surgery must be performed by an Oncologist Gynecologist or an Oncologist Surgeon because inadequate surgery performed by another specialist has been reported in 75% of cases. In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10-30% of all cases, and systematic limphadenectomy, necessary to be able to obtain an adequate surgical staging. Fertility-sparing surgery will be performed in certain cases, the procedure should include a detailed inspection of the contralateral ovary and also negative for malignancy omentum and ovary biopsy. Until now, laparoscopy for diagnostic-staging surgery is not well known as a recommended method. The recommended chemotherapy is based on platin and taxanes for 6 cycles, except in Stage IA, IB and grade 1, which have a good prognosis. In advanced stages, primary cytoreduction is recommended as initial treatment. Minimal invasion surgery is not a recommended procedure for the treatment of advanced ovarian cancer. Radiotherapy can be used to palliate symptoms. Follow up of the patients every 2-4 months for 2 years, every 3-6 months for 3 years and anually after the 5th year is recommended. Evaluation of quality of life of the patient must be done periodically. In the present, there is not a standardized screening method. Diagnosis in early stages means a better survival. Standardized treatment includes primary surgery with the objective to perform an optimal cytoreduction followed by chemotherapy Treatment must be individualized according to each patient. Radiotherapy can be indicated to palliate symptoms.

Expression of preoperative KISS1 gene in tumor tissue with epithelial ovarian cancer and its prognostic value.

PubMed

Cao, Fang; Chen, Liping; Liu, Manhua; Lin, Weiwei; Ji, Jinlong; You, Jun; Qiao, Fenghai; Liu, Hongbin

2016-11-01

Our study aimed to elucidate the role of Kisspeptin (KISS1) in tumor tissues of patients with epithelial ovarian cancer (EOC) and investigate the prognostic value of this biomarker.Forty EOC patients and 20 uterine fibroids female patients with healthy ovaries undergoing cytoreductive surgery between January 2010 and January 2014 in our hospital were enrolled in this study. KISS1 expression in tumor and normal tissues was detected. Correlations between clinic-pathologic variables and KISS1 expression in EOC tissues and the prognostic value of KISS1 for overall survival were evaluated.During the follow-up of 11.2 to 62.1 months, the overall survival rate and mean survival time were 28.9% (11/38) and 38.35 ± 2.84 months. Preoperative KISS1 mRNA was higher in tumor tissue than in normal tissue (P <0.001), and it was associated with histologic grade of tumor, surgical FIGO stage, metastasis, and residual tumor size (all P <0.05). Multivariate survival analysis indicated significant influence of residual tumor size (HR = 2.357, P = 0.039) and preoperative KISS1 mRNA (HR = 0.0001, P <0.001) on mean survival time. Patients with low KISS1 mRNA expression had shorter survival time than those with high expression (P = 0.001).Preoperative KISS1 mRNA was a potential prognostic biomarker for EOC, and high preoperative KISS1 expression indicated a favorable prognosis.

Reduced m6A mRNA methylation is correlated with the progression of human cervical cancer

PubMed Central

Kong, Beihua; Song, Chen; Cong, Jianglin; Hou, Jianqing; Wang, Shaoguang

2017-01-01

The m6A mRNA methylation involves in mRNA splicing, degradation and translation. Recent studies have revealed that reduced m6A mRNA methylation might promote cancer development. However, the role of m6A mRNA methylation in cervical cancer development remains unknown. Therefore, we investigated the role of m6A methylation in cervical cancer in the current study. We first evaluated the m6A mRNA methylation level in 286 pairs of cervical cancer samples and their adjacent normal tissues by dot blot assay. Then the role of m6A on patient survival rates and cervical cancer progression were assessed. The m6A level was significantly reduced in the cervical cancer when comparing with the adjacent normal tissue. The m6A level reduction was significantly correlated with the FIGO stage, tumor size, differentiation, lymph invasion and cancer recurrence. It was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with cervical cancer. Reducing m6A level via manipulating the m6A regulators expression promoted cervical cancer cell proliferation. And increasing m6A level significantly suppressed tumor development both in vitro and in vivo. Our results showed that the reduced m6A level is tightly associated with cervical cancer development and m6A mRNA methylation might be a potential therapeutic target in cervical cancer. PMID:29228737

A Selected Immunohistochemical Panel Aids in Differential Diagnosis and Prognostic Stratification of Subtypes of High-grade Endometrial Carcinoma: A Clinicopathologic and Immunohistochemical Study at a Single Institution.

PubMed

Taskin, Orhun Çiğ; Onder, Semen; Topuz, Samet; Sozen, Hamdullah; Sen, Fatma; Ilhan, Ridvan; Yavuz, Ekrem

This study aimed to investigate whether a selected immunohistochemical panel (estrogen receptor, p53, ARID1A, PPP2R1A, HNF-1β) could contribute to the diagnostic process of high-grade endometrial carcinomas (HG-ECs). We also aimed to analyze the correlation of these immunohistochemical results with several morphologic variables and survival data. After revising the diagnosis of 78 HG-ECs, immunohistochemical analysis was performed for each case. After immunohistochemical analysis, a specific diagnosis of prototypic HG-EC was established in most of the cases that were uncertain due to morphologic ambiguity. In the univariate analysis, older patient age, type II morphology, undifferentiated carcinoma and carcinosarcoma type of histology, altered p53 immunostaining, strong membranous staining of PPP2R1A, presence of lymphovascular invasion in serous carcinoma, and microcystic, elongated, and fragmented-type infiltration pattern in endometrioid carcinoma were significantly related to poor prognosis. In the multivariate analysis, only older patient age and carcinosarcoma or undifferentiated/dedifferentiated carcinoma type histology were found to be significantly poor prognostic factors (P=0.011), whereas advanced FIGO stage and type II histology were found to be correlated with poor prognosis, but did not reach statistical significance. We suggest that immunohistochemistry should be used in the differential diagnosis of HG-ECs, especially those with ambiguous morphology. Markers used in this study made a valuable contribution to the diagnostic process as well as prediction of prognosis.

Genotype distribution of cervical human papillomavirus DNA in women with cervical lesions in Bioko, Equatorial Guinea

PubMed Central

García-Espinosa, Benjamín; Nieto-Bona, Ma Paz; Rueda, Sonsoles; Silva-Sánchez, Luís Fernando; Piernas-Morales, Ma Concepción; Carro-Campos, Patricia; Cortés-Lambea, Luís; Moro-Rodríguez, Ernesto

2009-01-01

Background The HVP vaccine is a useful tool for preventing cervical cancer. The purpose of this study is to determine the most frequent HPV genotypes in Equatorial Guinea in order to develop future vaccination strategies to apply in this country. Methods A campaign against cervical cancer was carried out in the area on a total of 1,680 women. 26 of the women, following cytological screening, were treated surgically with a loop electrosurgical excision procedure (LEEP). Cases were studied histologically and were genotyped from paraffin blocks by applying a commercial kit that recognized 35 HPV types. Results Cytological diagnoses included 17 HSIL, 1 LSIL, 5 ASC-H and 3 AGUS. Histological diagnosis resulted in 3 cases of microinvasive squamous cell carcinoma stage IA of FIGO, 9 CIN-3, 8 CIN-2, 2 CIN-1, 3 flat condylomas and mild dysplasia of the endocervical epithelium. Fifteen of twenty-five cases genotyped were positive for HPV (60%). HPV 16 and 33 were identified in four cases each, HPV 58 in two other cases, and HPV 18, 31, 52, and 82 in one case, with one HPV 16 and 58 coinfection. Conclusion The frequency of HPV types in the African area varies in comparison to other regions, particularly in Europe and USA. Vaccination against the five most common HPV types (16, 33, 58, 18, and 31) should be considered in the geographic region of West Africa and specifically in Equatorial Guinea. PMID:19740435

The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Jun-jun; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011

HOX transcript antisense RNA (HOTAIR) is a well-known long non-coding RNA (lncRNA) whose dysregulation correlates with poor prognosis and malignant progression in many forms of cancer. Here, we investigate the expression pattern, clinical significance, and biological function of HOTAIR in serous ovarian cancer (SOC). Clinically, we found that HOTAIR levels were overexpressed in SOC tissues compared with normal controls and that HOTAIR overexpression was correlated with an advanced FIGO stage and a high histological grade. Multivariate analysis revealed that HOTAIR is an independent prognostic factor for predicting overall survival in SOC patients. We demonstrated that HOTAIR silencing inhibited A2780 andmore » OVCA429 SOC cell proliferation in vitro and that the anti-proliferative effects of HOTAIR silencing also occurred in vivo. Further investigation into the mechanisms responsible for the growth inhibitory effects by HOTAIR silencing revealed that its knockdown resulted in the induction of cell cycle arrest and apoptosis through certain cell cycle-related and apoptosis-related proteins. Together, these results highlight a critical role of HOTAIR in SOC cell proliferation and contribute to a better understanding of the importance of dysregulated lncRNAs in SOC progression. - Highlights: • HOTAIR overexpression correlates with an aggressive tumour phenotype and a poor prognosis in SOC. • HOTAIR promotes SOC cell proliferation both in vitro and in vivo. • The proliferative role of HOTAIR is associated with regulation of the cell cycle and apoptosis.« less

Oxygenation in cervical cancer and normal uterine cervix assessed using blood oxygenation level-dependent (BOLD) MRI at 3T.

PubMed

Hallac, Rami R; Ding, Yao; Yuan, Qing; McColl, Roderick W; Lea, Jayanthi; Sims, Robert D; Weatherall, Paul T; Mason, Ralph P

2012-12-01

Hypoxia is reported to be a biomarker for poor prognosis in cervical cancer. However, a practical noninvasive method is needed for the routine clinical evaluation of tumor hypoxia. This study examined the potential use of blood oxygenation level-dependent (BOLD) contrast MRI as a noninvasive technique to assess tumor vascular oxygenation at 3T. Following Institutional Review Board-approved informed consent and in compliance with the Health Insurance Portability and Accountability Act, successful results were achieved in nine patients with locally advanced cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA] and three normal volunteers. In the first four patients, dynamic T₂*-weighted MRI was performed in the transaxial plane using a multi-shot echo planar imaging sequence whilst patients breathed room air followed by oxygen (15 dm³/min). Later, a multi-echo gradient echo examination was added to provide quantitative R₂* measurements. The baseline T₂*-weighted signal intensity was quite stable, but increased to various extents in tumors on initiation of oxygen breathing. The signal in normal uterus increased significantly, whereas that in the iliacus muscle did not change. R₂* responded significantly in healthy uterus, cervix and eight cervical tumors. This preliminary study demonstrates that BOLD MRI of cervical cancer at 3T is feasible. However, more patients must be evaluated and followed clinically before any prognostic value can be determined. Copyright © 2012 John Wiley & Sons, Ltd.

Clinical outcomes from an innovative protocol using serial ultrasound imaging and a single MR image to guide brachytherapy for locally advanced cervix cancer.

PubMed

van Dyk, Sylvia; Narayan, Kailash; Bernshaw, David; Kondalsamy-Chennakesavan, Srinivas; Khaw, Pearly; Lin, Ming Yin; Schneider, Michal

The aim of this study was to report clinical outcomes in a series of patients who underwent serial ultrasound and a single MRI to plan and verify intracavitary brachytherapy. Data for patients who were referred for curative intent radiotherapy for International Federation of Gynecology and Obstetrics (FIGO) Stage 1-1V cervix cancer between January 2007 and March 2012 were analyzed. All patients received external beam radiotherapy with concurrent chemotherapy and sequential high-dose rate brachytherapy. Brachytherapy was planned and verified using serial ultrasound imaging and a single MRI. Data from 191 patients were available for analyses. The median (range) followup time was 5.08 (0.25-8.25) years. Five-year local control, failure-free survival, cancer-specific survival, and overall survival were 86%, 57.3%, 70% and 63%, respectively. Mean (standard deviation) combined external beam radiotherapy and brachytherapy target doses, equivalent to doses in 2 Gy fractions were 80.4 Gy10 (3.89), median (range) 80 (49-96) Gy10. Grade 3 or greater gastrointestinal, genitourinary, or vaginal late toxicity occurred in 3%, 1.6%, and 2% of patients, respectively. Survival, patterns of failure, and late complication rates were similar to published series of MRI/CT-based brachytherapy practices. This large study demonstrates that favorable treatment outcomes can be obtained using a pragmatic and innovative combination of ultrasound and MR imaging. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Genotype distribution of cervical human papillomavirus DNA in women with cervical lesions in Bioko, Equatorial Guinea.

PubMed

García-Espinosa, Benjamín; Nieto-Bona, Ma Paz; Rueda, Sonsoles; Silva-Sánchez, Luís Fernando; Piernas-Morales, Ma Concepción; Carro-Campos, Patricia; Cortés-Lambea, Luís; Moro-Rodríguez, Ernesto

2009-09-09

The HVP vaccine is a useful tool for preventing cervical cancer. The purpose of this study is to determine the most frequent HPV genotypes in Equatorial Guinea in order to develop future vaccination strategies to apply in this country. A campaign against cervical cancer was carried out in the area on a total of 1,680 women. 26 of the women, following cytological screening, were treated surgically with a loop electrosurgical excision procedure (LEEP). Cases were studied histologically and were genotyped from paraffin blocks by applying a commercial kit that recognized 35 HPV types. Cytological diagnoses included 17 HSIL, 1 LSIL, 5 ASC-H and 3 AGUS. Histological diagnosis resulted in 3 cases of microinvasive squamous cell carcinoma stage IA of FIGO, 9 CIN-3, 8 CIN-2, 2 CIN-1, 3 flat condylomas and mild dysplasia of the endocervical epithelium. Fifteen of twenty-five cases genotyped were positive for HPV (60%). HPV 16 and 33 were identified in four cases each, HPV 58 in two other cases, and HPV 18, 31, 52, and 82 in one case, with one HPV 16 and 58 coinfection. The frequency of HPV types in the African area varies in comparison to other regions, particularly in Europe and USA. Vaccination against the five most common HPV types (16, 33, 58, 18, and 31) should be considered in the geographic region of West Africa and specifically in Equatorial Guinea.

Prediction of 5-year overall survival in cervical cancer patients treated with radical hysterectomy using computational intelligence methods.

PubMed

Obrzut, Bogdan; Kusy, Maciej; Semczuk, Andrzej; Obrzut, Marzanna; Kluska, Jacek

2017-12-12

Computational intelligence methods, including non-linear classification algorithms, can be used in medical research and practice as a decision making tool. This study aimed to evaluate the usefulness of artificial intelligence models for 5-year overall survival prediction in patients with cervical cancer treated by radical hysterectomy. The data set was collected from 102 patients with cervical cancer FIGO stage IA2-IIB, that underwent primary surgical treatment. Twenty-three demographic, tumor-related parameters and selected perioperative data of each patient were collected. The simulations involved six computational intelligence methods: the probabilistic neural network (PNN), multilayer perceptron network, gene expression programming classifier, support vector machines algorithm, radial basis function neural network and k-Means algorithm. The prediction ability of the models was determined based on the accuracy, sensitivity, specificity, as well as the area under the receiver operating characteristic curve. The results of the computational intelligence methods were compared with the results of linear regression analysis as a reference model. The best results were obtained by the PNN model. This neural network provided very high prediction ability with an accuracy of 0.892 and sensitivity of 0.975. The area under the receiver operating characteristics curve of PNN was also high, 0.818. The outcomes obtained by other classifiers were markedly worse. The PNN model is an effective tool for predicting 5-year overall survival in cervical cancer patients treated with radical hysterectomy.

The Improved Dual-view Field Goniometer System FIGOS

PubMed Central

Schopfer, Jürg; Dangel, Stefan; Kneubühler, Mathias; Itten, Klaus I.

2008-01-01

In spectrodirectional Remote Sensing (RS) the Earth's surface reflectance characteristics are studied by means of their angular dimensions. Almost all natural surfaces exhibit an individual anisotropic reflectance behaviour due to the contrast between the optical properties of surface elements and background and the geometric surface properties of the observed scene. The underlying concept, which describes the reflectance characteristic of a specific surface area, is called the bidirectional reflectance distribution function (BRDF). BRDF knowledge is essential for both correction of directional effects in RS data and quantitative retrieval of surface parameters. Ground-based spectrodirectional measurements are usually performed with goniometer systems. An accurate retrieval of the bidirectional reflectance factors (BRF) from field goniometer measurements requires hyperspectral knowledge of the angular distribution of the reflected and the incident radiation. However, prior to the study at hand, no operational goniometer system was able to fulfill this requirement. This study presents the first dual-view field goniometer system, which is able to simultaneously collect both the reflected and the incident radiation at high angular and spectral resolution and, thus, providing the necessary spectrodirectional datasets to accurately retrieve the surface specific BRF. Furthermore, the angular distribution of the incoming diffuse radiation is characterized for various atmospheric conditions and the BRF retrieval is performed for an artificial target and compared to laboratory spectrodirectional measurement results obtained with the same goniometer system. Suggestions for further improving goniometer systems are given and the need for intercalibration of various goniometers as well as for standardizing spectrodirectional measurements is expressed. PMID:27873805

The Improved Dual-view Field Goniometer System FIGOS.

PubMed

Schopfer, Jürg; Dangel, Stefan; Kneubühler, Mathias; Itten, Klaus I

2008-08-28

In spectrodirectional Remote Sensing (RS) the Earth's surface reflectance characteristics are studied by means of their angular dimensions. Almost all natural surfaces exhibit an individual anisotropic reflectance behaviour due to the contrast between the optical properties of surface elements and background and the geometric surface properties of the observed scene. The underlying concept, which describes the reflectance characteristic of a specific surface area, is called the bidirectional reflectance distribution function (BRDF). BRDF knowledge is essential for both correction of directional effects in RS data and quantitative retrieval of surface parameters. Ground-based spectrodirectional measurements are usually performed with goniometer systems. An accurate retrieval of the bidirectional reflectance factors (BRF) from field goniometer measurements requires hyperspectral knowledge of the angular distribution of the reflected and the incident radiation. However, prior to the study at hand, no operational goniometer system was able to fulfill this requirement. This study presents the first dual-view field goniometer system, which is able to simultaneously collect both the reflected and the incident radiation at high angular and spectral resolution and, thus, providing the necessary spectrodirectional datasets to accurately retrieve the surface specific BRF. Furthermore, the angular distribution of the incoming diffuse radiation is characterized for various atmospheric conditions and the BRF retrieval is performed for an artificial target and compared to laboratory spectrodirectional measurement results obtained with the same goniometer system. Suggestions for further improving goniometer systems are given and the need for intercalibration of various goniometers as well as for standardizing spectrodirectional measurements is expressed.

Sublingual misoprostol and hyperpyrexia: case report with temperature curve.

PubMed

Tolefac, Paul Nkemtendong; Minkande, Jacqueline Ze

2017-07-26

Misoprostol has a wide range of applications in obstetrics and gynaecology. It is widely recommended by WHO, FIGO and ACOG for the treatment of postpartum haemorrhage due to it safety and cost-effectiveness. However, usage might be associated to hyperpyrexia and shivering. We present a 30 year old Cameroonian female gravida 1 para 1 who had a vaginal delivery at 40 weeks of gestation complicated by primary postpartum haemorrhage (PPH). PPH was managed by sublingual misoprostol that induced shivering and hyperpyrexia managed successfully with paracetamol and cooling. The occurrence of fever and shivering should be kept in mind when administering misoprostol for PPH.

Expression of P-Akt, NFkappaB and their correlation with human papillomavirus infection in cervical carcinoma.

PubMed

Du, C X; Wang, Y

2012-01-01

To investigate the expression of P-Akt and NFkappaB and their correlation with human papillomavirus (HPV) infection in cervical carcinoma. Expression of P-Akt and NFkappaB was detected by an immunohistochemical SP technique with HPV DNA detetion by PCR in 26 cases of cervical carcinoma tissues, 18 cases of cervical intraepithelial neoplasia tissues (CINI / n = 5, CINII / n = 3, CINIII / n = 10) and 19 cases of chronic cervicitis tissues. The different expressions of P-Akt and NFkappaB were compared in different pathological types of cervical carcinoma (cervical squamous cell carcinoma, cervical adenocarcinoma), different pathological grading (high, medium, poorly differentiated) and different clinical stage (FIGO I to IV). The relationships between P-Akt and NFkappaB, respectively, with HPV infection in cervical carcinoma were analyzed. The positive expression rate of P-Akt in chronic cervicitis tissues, CIN and cervical carcinoma tissues was 21.05%, 66.67%, and 92.31%, respectively. There was no obvious difference in the expression of P-Akt in cervical carcinoma in different pathological types or in pathological grading and no obvious difference in different clinical stages. The positive expression rate of NFkappaB in chronic cervicitis tissues, CIN and cervical carcinoma tissues was 10.52%, 72.22% and 96.15%, respectively; there was no statistically significant difference among the groups for different pathological types and there was no obvious difference in different pathological grading or different clinical stage. There was an obviously positive correlation between P-Akt and NFkappaB expression rate and degree of disease (r = 0.998, p < 0.05). Cervical carcinoma and CIN cases totaled 44; the positive expression rate of P-Akt was 87.55% in 32 cases of positive HPV-DNA of the 44 cases, and the positive expression rate of P-Akt was only 16.70% in 12 cases of negative HPV-DNA of the 44 cases. The positive expression rate of NFkappaB was obviously higher in the HPV DNA positive than in the HPV-DNA negative cases. There was a statistically significant difference among the groups (p < 0.05). The positive expression rate of P-Akt and NFkappaB was closely related with cervical disease extent, and closely related with HPV infection in cervical carcinoma. This study suggests that P-Akt and NFkappaB more probably play an important role in the occurrence of cervical carcinoma.

Pelvic lymph node dissection in early ovarian cancer: success of retrieval of lymph nodes by individual lymph node groups in respect to pelvic laterality.

PubMed

Mujezinović, Faris; Takac, Iztok

2010-08-01

To evaluate the differences in number of harvested retroperitoneal pelvic lymph nodes by specific lymph node regions in respect to pelvic laterality. We extracted cases of early ovarian cancer (EOC) with lymphadenectomy from the medical database which were treated at our institution in the period between 1994 and 2008. Recommendations of FIGO and EGSOC (European Guidelines for Staging in Ovarian Cancer) for staging of ovarian malignancies were followed. Stage of the disease was established on the basis of intra-abdominal condition which we found during surgery and histopathologic status of retroperitoneal lymph nodes (LN). For each case and every LN group, we subtracted the number of dissected lymph nodes on the left side from the number of dissected lymph nodes on the right side of the pelvis. The result would represent the difference between number of removed LN on each side of the pelvis for specific LN group. A negative difference means that a greater number of LN was extracted from the left side and a positive difference that the greater number of LN was extracted from the right side of the pelvis. We used Wilcoxon signed-rank test for statistical analysis of differences. 48 cases with EOC underwent lymphadenectomy. In three cases, metastatic retroperitoneal pelvic lymph nodes were found. There were 79.1%, 50.0%, 45.8%, 93.8%, 52.1%, 60.4% and 70.8% of cases with left-right difference in number of removed lymph nodes in external iliac region, common iliac region, presacralic, above obturator nerve, under obturator nerve, lateral from the external ilac vessels and lateral from the common iliac vessels nodal group, respectively. The mean differences between left and right groups were in the range from 2 to 4 lymph nodes. There was no identifiable bias toward either side of the pelvis for any of the analyzed lymph node groups. There is a right and left prevalence of retrieved LN by individual LN regions in the pelvis that could be influenced by asymmetry in right-left pelvic LN distribution. However, we did not find any evidence that the observed imbalance is, on average, directed toward either side of the pelvis. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Comparison of classic terminology with the FIGO PALM-COEIN system for classification of the underlying causes of abnormal uterine bleeding.

PubMed

Töz, Emrah; Sancı, Muzaffer; Özcan, Aykut; Beyan, Emrah; İnan, Abdurrahman H

2016-06-01

To compare classic terminology and the PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory disorders, endometrium, iatrogenic, and not classified) classification system among women who underwent surgery for abnormal uterine bleeding (AUB), and to subclassify the components of the PALM group for future studies. In a retrospective study, data were obtained for nonpregnant women aged 18-55years who underwent hysterectomy, myomectomy, or polypectomy for AUB at a center in Turkey in 2014. The patients were retrospectively classified according to the PALM-COEIN system, and the two terminologies were compared. A total of 471 women were included. The term "hypermenorrhea" covered 15 different pathology combinations, "menorrhagia" nine, "metrorrhagia" 14, and "menometrorrhagia" 18. Of 92 patients with polyp, 5 (5.4%) had two polyps and 1 (1.1%) had three. Of 146 patients with adenomyosis, 131 (89.7%) had diffuse adenomyosis and 12 (8.2%) had adenomyoma. Of 309 patients with myoma uteri, 108 (34.9%) had submucous myoma and 201 (65.1%) had other types of myoma. Classic terminology for AUB is insufficient and confusing with respect to etiologic pathologies among nonpregnant women of reproductive age. Widespread adoption of the PALM-COEIN system for AUB classification will facilitate more meaningful communication among both clinicians and investigators, and clarify the populations that should be evaluated in clinical trials, thereby enhancing communication with patients. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Roles of posttherapy 18F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy.

PubMed

Liu, Feng-Yuan; Su, Tzu-Pei; Wang, Chun-Chieh; Chao, Angel; Chou, Hung-Hsueh; Chang, Yu-Chen; Yen, Tzu-Chen; Lai, Chyong-Huey

2018-07-01

To assess the clinical roles of [ 18 F]fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) performed 2-3 months after completion of concurrent chemoradiotherapy (CCRT), along with pretherapy characteristics, in patients with advanced squamous cell carcinoma of the uterine cervix enrolled in a prospective randomized clinical trial. Posttherapy PET/CT in patients with advanced FIGO stage or positive pelvic or para-aortic lymph node (PALN) defined on pretherapy PET/CT was classified as positive, equivocal, or negative. Overall survival (OS) rates between patients with different PET/CT results are compared. Pretherapy characteristics are examined for association with posttherapy PET/CT results and for prognostic significance in patients with equivocal or negative PET/CT. PET/CT scans (n = 55) were positive, equivocal and negative in 9, 13 and 33 patients, respectively. All patients with positive scans were confirmed to have residual or metastatic disease and died despite salvage therapies. There is a significant OS difference between patients with positive and equivocal scans (P < .001) but not between patients with equivocal and negative scans (P = .411). Positive pretherapy PALN is associated with positive posttherapy PET/CT (P = .033) and predicts a poorer survival in patients with equivocal or negative posttherapy PET/CT (P < .001). Positive PET/CT 2-3 months posttherapy implies treatment failure and novel therapy is necessary to improve outcomes for such patients. A more intense posttherapy surveillance may be warranted in patients with positive pretherapy PALN.

Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome

PubMed Central

Nebgen, Denise R.; Lu, Karen H.; Rimes, Sue; Keeler, Elizabeth; Broaddus, Russell; Munsell, Mark F.; Lynch, Patrick M.

2015-01-01

Objective Endometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5 years. Methods We retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1–2 years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation. Results Out of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected. Conclusions Combined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1–2 years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer. PMID:25149916

Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome.

PubMed

Nebgen, Denise R; Lu, Karen H; Rimes, Sue; Keeler, Elizabeth; Broaddus, Russell; Munsell, Mark F; Lynch, Patrick M

2014-10-01

Endometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5 years. We retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1-2 years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation. Out of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy-one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected. Combined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1-2 years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

8-oxo-7,8-dihydroguanine level - the DNA oxidative stress marker - recognized by fluorescence image analysis in sporadic uterine adenocarcinomas in women.

PubMed

Postawski, Krzysztof; Przadka-Rabaniuk, Dorota; Piersiak, Tomasz

2013-01-01

In the case of carcinogenesis in human endometrium no information exists on tissue concentration of 8-oxo-7,8-dihydroguanine, the DNA oxidative stress marker This was the main reason to undertake the investigation of this DNA modification in human uterine estrogen-dependent tissue cancers. In order to estimate the level of oxidative damage, 8-oxo-7,8-dihydroguanine was determined directly in cells of tissue microscope slides using OxyDNA Assay Kit, Fluorometric. Cells were investigated under confocal microscope. Images of individual cells were captured by computer-interfaced digital photography and analyzed for fluorescence intensities (continuous inverted 8-bit gray-scale = 0 [black]-255 [white]). Fluorescence scores were calculated for each of 13 normal endometrial samples and 31 uterine adenocarcinoma specimens. Finally the level of the oxidative stress marker was also analyzed according to histological and clinical features of the neoplasms. The obtained data revealed that: 8-oxo-7,8-dihydroguanine levels were higher in uterine adenocarcinomas than in normal endometrial samples (48,32 vs. 38,64; p<0,001); in contrast to normal endometrium there was no correlation between age and DNA oxidative modification content in uterine cancer; highest mean fluorescence intensity was recognized in G2 endometrial adenocarcinomas; level of 8-oxo-7,8-dihydroguanine does not depend on Body Mass Index (BMI) and cancer uterine wall infiltration or tumor FIGO stage. Our study indicates that accumulation of the oxidized DNA base may contribute to the development of endometrial neoplasia, however oxidative DNA damage does not seem to increase with tumor progression.

Identification and characterization of cancer stem-like cells from primary carcinoma of the cervix uteri.

PubMed

Feng, Dingqing; Peng, Cheng; Li, Cairong; Zhou, Ying; Li, Min; Ling, Bin; Wei, Haiming; Tian, Zhigang

2009-11-01

Like many other solid tumors, cervical cancer contains a heterogeneous population of cancer cells. Several investigators have identified putative stem cells from solid tumors and cancer cell lines via the capacity to self renew and drive tumor formation. The aim of this study was to identify and characterize a cancer stem-like cell population from primary carcinoma of the cervix uteri. Cervical carcinoma from 19 patients staged I-II following International Federation of Gynecology and Obstetrics (FIGO) criteria were disaggregated and subjected to growth conditions selective for stem cells. Eight of nineteen tumor-derived cultures encompassed stem-like cells capable of self-renewal, extensive proliferation as clonal non-adherent spherical clusters. Cell markers of spheroid were identified as CD44+CK17+. Cell survival assays showed the sphere-forming cells were only 48% inhibited by doxorubicin whereas 78% inhibited by paclitaxel. Chemo-resistance may partly attribute to the exclusive expression of ABC transporter. To investigate the tumorigenicity of these stem-like cells, xenoengraftment of 10(5) dissociated spheroid cells allowed full recapitulation of the original tumor, whereas the same amount of tumor cells without non-adherent spheroid selection remained non-tumorigenic. Stemness properties of these spheroid cells were further established by reverse transcription-PCR and Western blotting, demonstrating the expression of embryonic and adult stemness-related genes (Oct-4, Piwil2, C-myc, Stat3 and Sox2). Based on these findings, we assert that cervical cancer contain a subpopulation of tumor initiating cells with stem-like properties, thus facilitating the approach to therapeutic strategies aimed at eradicating the tumorigenic subpopulation within cervical cancer.

Impact of point A asymmetry on local control and survival for low dose-rate (LDR) brachytherapy in cervical cancer.

PubMed

Opfermann, Krisha J; Wahlquist, Amy; Watkins, John; Kohler, Matthew; Jenrette, Joseph

2012-03-01

To evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local control (LC), disease-free survival (DFS) and/or overall survival (OS). A retrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpostat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest. The records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a median survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with statistically significantly inferior LC (p = 0.035) and inferior DFS (p = 0.011) for patients with mean Point A dose of > 80 Gy. Insufficient evidence existed to conclude an association with OS. LDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC.

Impact of point A asymmetry on local control and survival for low dose-rate (LDR) brachytherapy in cervical cancer

PubMed Central

Wahlquist, Amy; Watkins, John; Kohler, Matthew; Jenrette, Joseph

2012-01-01

Purpose To evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local control (LC), disease-free survival (DFS) and/or overall survival (OS). Material and methods A retrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpostat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest. Results The records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a median survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with statistically significantly inferior LC (p = 0.035) and inferior DFS (p = 0.011) for patients with mean Point A dose of > 80 Gy. Insufficient evidence existed to conclude an association with OS. Conclusions LDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC. PMID:23346133

Loss of GPER identifies new targets for therapy among a subgroup of ERα-positive endometrial cancer patients with poor outcome

PubMed Central

Krakstad, C; Trovik, J; Wik, E; Engelsen, I B; Werner, H M J; Birkeland, E; Raeder, M B; Øyan, A M; Stefansson, I M; Kalland, K H; Akslen, L A; Salvesen, H B

2012-01-01

Background: The G protein-coupled oestrogen receptor, GPER, has been suggested as an alternative oestrogen receptor. Our purpose was to investigate the potential of GPER as a prognostic and predictive marker in endometrial carcinoma and to search for new drug candidates to improve treatment of aggressive disease. Materials and method: A total of 767 primary endometrial carcinomas derived from three patient series, including an external dataset, were studied for protein and mRNA expression levels to investigate and validate if GPER loss identifies poor prognosis and new targets for therapy in endometrial carcinoma. Gene expression levels, according to ERα/GPER status, were used to search the connectivity map database for small molecular inhibitors with potential for treatment of metastatic disease for receptor status subgroups. Results: Loss of GPER protein is significantly correlated with low GPER mRNA, high FIGO stage, non-endometrioid histology, high grade, aneuploidy and ERα loss (all P-values ⩽0.05). Loss of GPER among ERα-positive patients identifies a subgroup with poor prognosis that until now has been unrecognised, with reduced 5-year survival from 93% to 76% (P=0.003). Additional loss of GPER from primary to metastatic lesion counterparts further supports that loss of GPER is associated with disease progression. Conclusion: These results support that GPER status adds clinically relevant information to ERα status in endometrial carcinoma and suggest a potential for new inhibitors in the treatment of metastatic endometrial cancers with ERα expression and GPER loss. PMID:22415229

Prognostic and Clinicopathological Significance of ARID1A in Endometrium-Related Gynecological Cancers: A Meta-Analysis.

PubMed

Liu, Guangquan; Xu, Pengfei; Fu, Ziyi; Hua, Xiangdong; Liu, Xiaoguang; Li, Wenqu; Zhang, Mi; Wu, Jiacong; Wen, Juan; Xu, Juan; Jia, Xuemei

2017-12-01

The tumor suppressor gene, AT Rich Interactive Domain 1A (ARID1A) mutation has been reported in a variety of cancers, especially the endometrium-related gynecological cancers, including the ovarian clear cell carcinoma, ovarian endometrioid carcinoma, and uterine endometrioid carcinoma. However, the prognostic value of ARID1A in endometrium-related gynecological cancers is still inconclusive. Therefore, we performed this meta-analysis to evaluate the clinical significance of ARID1A in endometrium-related gynecological cancers. By systematically searching all the relevant studies from Pubmed, Cochrane Library, and Web of Science up to September 2016, 11 studies with 1,432 patients were included. All the study characteristics and the prognostic data were extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using the fixed-effect or random-effect model. Our results indicated that negative ARID1A expression predicted shorter Progression free survival (PFS, HR, 1.84; 95%CI, 1.32-2.57, P = 0.000) of patients with endometrium related gynecological cancers, especially the patiently with OCCC and the patients in Japan. Besides, a marginal trend towards the same direction was found in the Overall analysis (OS, HR, 1.34; 95%CI, 0.93-1.93, P = 0.112). Furthermore, the significant correlation was achieved between the negative ARID1A expression and the FIGO stage of endometrium-related gynecological cancers, but not the other characteristics. J. Cell. Biochem. 118: 4517-4525, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Management and prognosis of patients with brain metastasis from gestational trophoblastic neoplasia: a 24-year experience in Peking union medical college hospital.

PubMed

Xiao, Changji; Yang, Junjun; Zhao, Jing; Ren, Tong; Feng, Fengzhi; Wan, Xirun; Xiang, Yang

2015-04-28

The optimal treatment for patients with brain metastasis from gestational trophoblastic neoplasia (GTN) has not been established. This study aims to investigate the clinical characteristics and the management of brain metastasis from GTN in relation to patients' outcomes. We retrospectively investigated 109 GTN patients with brain metastasis treated at Peking Union Medical College Hospital from January 1990 to December 2013. Patients mainly received multiagent chemotherapy with florouracil or floxuridine, dactinomycin, etoposide, and vincristine (FAEV) combined with intrathecal methotrexate with or without surgery. In the 109 patients, sixty-two (56.1%) patients presented for primary therapy and 47 patients had failed chemotherapy elsewhere. Eight early demise patients who died before or during first cycle of chemotherapy were excluded from analysis. The median follow-up time was 47 months (range 9-180 months). The overall 5-year survival rate (OS) was 71.1%, while the OS rate for patients receiving primary chemotherapy in our hospital was 85.5%, and this fell to 51.9% in patients with failure multidrug chemotherapy elsewhere. Multivariate analysis demonstrated that International Federation of Gynecology and Obstetrics (FIGO) scores over 12 (Hazard ratio-HR 1.279, 95% CI 1.061-1.541, P = 0.010), failure of previous multidrug chemotherapy (HR 3.177, 95% CI 1.277-7.908, P = 0.013), and concurrent renal metastasis (HR 2.654, 95% CI 1.125-6.261, P = 0.026) were the risk factors of overall survival in patients with brain metastases from GTN. Patients with brain metastasis from GTN have favorable outcome by multidrug chemotherapy and adjuvant therapies. Nevertheless, the prognosis is poor if the patients had previous multidrug failure chemotherapy history, concomitant with renal metastasis, or FIGO score over 12. Initial treatment with FAEV combined with intrathecal methotrexate chemotherapy can bring bright prospect to patients with brain metastases from GTN.

Chemoradiation With Concomitant Boosts Followed by Radical Surgery in Locally Advanced Cervical Cancer: Long-term Results of the ROMA-2 Prospective Phase 2 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferrandina, Gabriella, E-mail: gabriella.ferrandina@libero.it; Gambacorta, Antonietta; Gallotta, Valerio

Purpose: This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. Methods and Materials: Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatinmore » (20 mg/m{sup 2}, days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m{sup 2}/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). Results: pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. Conclusions: Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very encouraging local control rate, with acceptable toxicity.« less

Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Creutzberg, Carien L., E-mail: c.l.creutzberg@lumc.nl; Stiphout, Ruud G.P.M. van; Nout, Remi A.

Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variablesmore » which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT after surgery. These models facilitate decision support in daily clinical practice and can be used for patient counseling and shared decision making, selecting patients who benefit most from adjuvant treatment, and generating new hypotheses.« less

[PROGNOSTIC MODELS IN MODERN MANAGEMENT OF VULVAR CANCER].

PubMed

Tsvetkov, Ch; Gorchev, G; Tomov, S; Nikolova, M; Genchev, G

2016-01-01

The aim of the research was to evaluate and analyse prognosis and prognostic factors in patients with squamous cell vulvar carcinoma after primary surgery with individual approach applied during the course of treatment. In the period between January 2000 and July 2010, 113 patients with squamous cell carcinoma of the vulva were diagnosed and operated on at Gynecologic Oncology Clinic of Medical University, Pleven. All the patients were monitored at the same clinic. Individual approach was applied to each patient and whenever it was possible, more conservative operative techniques were applied. The probable clinicopathological characteristics influencing the overall survival and recurrence free survival were analyzed. Univariate statistical analysis and Cox regression analysis were made in order to evaluate the characteristics, which were statistically significant for overall survival and survival without recurrence. A multivariate logistic regression analysis (Forward Wald procedure) was applied to evaluate the combined influence of the significant factors. While performing the multivariate analysis, the synergic effect of the independent prognostic factors of both kinds of survivals was also evaluated. Approaching individually each patient, we applied the following operative techniques: 1. Deep total radical vulvectomy with separate incisions for lymph dissection (LD) or without dissection--68 (60.18 %) patients. 2. En-bloc vulvectomy with bilateral LD without vulva reconstruction--10 (8.85%) 3. Modified radical vulvactomy (hemivulvectomy, patial vulvactomy)--25 (22.02%). 4. wide-local excision--3 (2.65%). 5. Simple (total /partial) vulvectomy--5 (4.43%) patients. 6. En-bloc resection with reconstruction--2 (1.77%) After a thorough analysis of the overall survival and recurrence free survival, we made the conclusion that the relapse occurrence and clinical stage of FIGO were independent prognostic factors for overall survival and the independent prognostic factors for recurrence free survival were: metastatic inguinal nodes (unilateral or bilateral), tumor size (above or below 3 cm) and lymphovascular space invasion. On the basis of these results we created two prognostic models: 1. A prognostic model of overall survival 2. A prognostic model for survival without recurrence. Following the surgical staging of the disease, were able to gather and analyse important clinicopathological indexes, which gave us the opportunity to form prognostic groups for overall survival and recurrence-free survival.

Preoperative prediction of lymph node metastasis and deep stromal invasion in women with invasive cervical cancer: prospective multicenter study using 2D and 3D ultrasound.

PubMed

Pálsdóttir, K; Fischerova, D; Franchi, D; Testa, A; Di Legge, A; Epstein, E

2015-04-01

To determine how various objective two-dimensional (2D) and three-dimensional (3D) ultrasound parameters allow prediction of deep stromal tumor invasion and lymph node involvement, in comparison to subjective ultrasound assessment, in women scheduled for surgery for cervical cancer. This was a prospective multicenter trial including 104 women with cervical cancer at FIGO Stages IA2-IIB, verified histologically. Patients scheduled for surgery underwent a preoperative ultrasound examination. The value of various 2D (size, color score) and 3D (volume, vascular indices) ultrasound parameters was compared to that of subjective assessment in the prediction of deep stromal tumor invasion and lymph node involvement. Histology obtained from radical hysterectomy or trachelectomy and pelvic lymphadenectomy was considered as the gold standard for assessment. All women underwent pelvic lymphadenectomy, with 99 (95%) undergoing subsequent radical surgery; five underwent only pelvic lymphadenectomy because of the presence of a positive sentinel lymph node. Women with deep stromal invasion or lymph node involvement had significantly larger tumors (diameter and volume) but there was no correlation with vascular indices measured on 3D ultrasound. Subjective evaluation was superior (AUC, 0.93; sensitivity, 90.5%; specificity, 97.2%) in the prediction of deep stromal invasion when compared to any objective measurement technique, with maximal tumor diameter at 20.5-mm cut-off (AUC, 0.83; sensitivity, 90.5%; specificity, 61.1%) and 3D tumor volume at 9.1-mm(3) cut-off (AUC, 0.85; sensitivity, 79.4%; specificity, 83.3%) providing the best performance among the objective parameters. Both subjective assessment and objective measurements were poorly predictive of lymph node involvement. In women with cervical cancer, subjective ultrasound evaluation allowed better prediction of deep stromal invasion than did objective measurements; however, neither subjective evaluation nor objective parameters were adequate to predict lymph node involvement. 3D vascular indices were ineffective in the prediction of advanced stages of the disease. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial.

PubMed

du Bois, Andreas; Kristensen, Gunnar; Ray-Coquard, Isabelle; Reuss, Alexander; Pignata, Sandro; Colombo, Nicoletta; Denison, Ursula; Vergote, Ignace; Del Campo, Jose M; Ottevanger, Petronella; Heubner, Martin; Minarik, Thomas; Sevin, Emmanuel; de Gregorio, Nikolaus; Bidziński, Mariusz; Pfisterer, Jacobus; Malander, Susanne; Hilpert, Felix; Mirza, Mansoor R; Scambia, Giovanni; Meier, Werner; Nicoletto, Maria O; Bjørge, Line; Lortholary, Alain; Sailer, Martin Oliver; Merger, Michael; Harter, Philipp

2016-01-01

Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advanced ovarian cancer. In this double-blind phase 3 trial, chemotherapy-naive patients (aged 18 years or older) with International Federation of Gynecology and Obstetrics (FIGO) IIB-IV ovarian cancer and upfront debulking surgery were stratified by postoperative resection status, FIGO stage, and planned carboplatin dose. Patients were randomly assigned (2:1) via an interactive voice or web-based response system to receive six cycles of carboplatin (AUC 5 mg/mL per min or 6 mg/mL per min) and paclitaxel (175 mg/m(2)) in addition to either 200 mg of nintedanib (nintedanib group) or placebo (placebo group) twice daily on days 2-21 of every 3-week cycle for up to 120 weeks. Patients, investigators, and independent radiological reviewers were masked to treatment allocation. The primary endpoint was investigator-assessed progression-free survival analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01015118. Between Dec 9, 2009, and July 27, 2011, 1503 patients were screened and 1366 randomly assigned by nine study groups in 22 countries: 911 to the nintedanib group and 455 to the placebo group. 486 (53%) of 911 patients in the nintedanib group experienced disease progression or death compared with 266 (58%) of 455 in the placebo group. Median progression-free survival was significantly longer in the nintedanib group than in the placebo group (17·2 months [95% CI 16·6-19·9] vs 16·6 months [13·9-19·1]; hazard ratio 0·84 [95% CI 0·72-0·98]; p=0·024). The most common adverse events were gastrointestinal (diarrhoea: nintedanib group 191 [21%] of 902 grade 3 and three [<1%] grade 4 vs placebo group nine [2%] of 450 grade 3 only) and haematological (neutropenia: nintedanib group 180 [20%] grade 3 and 200 (22%) grade 4 vs placebo group 90 [20%] grade 3 and 72 [16%] grade 4; thrombocytopenia: 105 [12%] and 55 [6%] vs 21 [5%] and eight [2%]; anaemia: 108 [12%] and 13 [1%] vs 26 [6%] and five [1%]). Serious adverse events were reported in 376 (42%) of 902 patients in the nintedanib group and 155 (34%) of 450 in the placebo group. 29 (3%) of 902 patients in the nintedanib group experienced serious adverse events associated with death compared with 16 (4%) of 450 in the placebo group, including 12 (1%) in the nintedanib group and six (1%) in the placebo group with a malignant neoplasm progression classified as an adverse event by the investigator. Drug-related adverse events leading to death occurred in three patients in the nintedanib group (one without diagnosis of cause; one due to non-drug-related sepsis associated with drug-related diarrhoea and renal failure; and one due to peritonitis) and in one patient in the placebo group (cause unknown). Nintedanib in combination with carboplatin and paclitaxel is an active first-line treatment that significantly increases progression-free survival for women with advanced ovarian cancer, but is associated with more gastrointestinal adverse events. Future studies should focus on improving patient selection and optimisation of tolerability. Boehringer Ingelheim. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extended mesometrial resection (EMMR): Surgical approach to the treatment of locally advanced cervical cancer based on the theory of ontogenetic cancer fields.

PubMed

Wolf, Benjamin; Ganzer, Roman; Stolzenburg, Jens-Uwe; Hentschel, Bettina; Horn, Lars-Christian; Höckel, Michael

2017-08-01

Based on ontogenetic-anatomic considerations, we have introduced total mesometrial resection (TMMR) and laterally extended endopelvic resection (LEER) as surgical treatments for patients with cancer of the uterine cervix FIGO stages I B1 - IV A. For a subset of patients with locally advanced disease we have sought to develop an operative strategy characterized by the resection of additional tissue at risk for tumor infiltration as compared to TMMR, but less than in LEER, preserving the urinary bladder function. We conducted a prospective single center study to evaluate the feasibility of extended mesometrial resection (EMMR) and therapeutic lymph node dissection as a surgical treatment approach for patients with cervical cancer fixed to the urinary bladder and/or its mesenteries as determined by intraoperative evaluation. None of the patients received postoperative adjuvant radiotherapy. 48 consecutive patients were accrued into the trial. Median tumor size was 5cm, and 85% of all patients were found to have lymph node metastases. Complete tumor resection (R0) was achieved in all cases. Recurrence free survival at 5years was 54.1% (95% CI 38.3-69.9). The overall survival rate was 62.6% (95% CI 45.6-79.6) at 5years. Perioperative morbidity represented by grade II and III complications (determined by the Franco-Italian glossary) occurred in 25% and 15% of patients, respectively. We demonstrate in this study the feasibility of EMMR as a surgical treatment approach for patients with locally advanced cervical cancer and regional lymph node invasion without the necessity for postoperative adjuvant radiation. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigating the clinical potential for 14-3-3 zeta protein to serve as a biomarker for epithelial ovarian cancer

PubMed Central

2013-01-01

Objective Recently, 14-3-3 zeta protein was identified as a potential serum biomarker of epithelial ovarian cancer (EOC). The goal of this study was to investigate the clinical potential of 14-3-3 zeta protein for monitoring EOC progression compared with CA-125 and HE4. Design Prospective follow-up study. Setting University of Pecs Medical Center Department of Obstetrics and Gynecology/Oncology (Pecs, Hungary). Population Thirteen EOC patients with advanced stage (FIGO IIb-IIIc) epithelial ovarian cancer that underwent radical surgery and received six consecutive cycles of first line chemotherapy (paclitaxel, carboplatin) in 21-day intervals. Methods Pre- and post-chemotherapy computed tomography (CT) scans were performed. Serum levels of CA-125, HE4, and 14-3-3 zeta protein were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative electrochemiluminescence assay (ECLIA). Main outcome measures Serum levels of CA-125, HE4, and 14-3-3 zeta protein, as well as lesion size according to pre- and post-chemotherapy CT scans. Results Serum levels of CA-125 and HE4 were found to significantly decrease following chemotherapy, and this was consistent with the decrease in lesion size detected post-chemotherapy. In contrast, 14-3-3 zeta protein levels did not significantly differ in healthy postmenopausal patients versus EOC patients. Conclusions Determination of CA-125 and HE4 serum levels for the determination of the risk of ovarian malignancy algorithm (ROMA) represents a useful tool for the prediction of chemotherapy efficacy for EOC patients. However, levels of 14-3-3 zeta protein were not found to vary significantly as a consequence of treatment. Therefore we question if 14-3-3 zeta protein is a reliable biomarker, which correlates with the clinical behavior of EOC. PMID:24238270

Lymphomas or leukemia presenting as ovarian tumors. An analysis of 42 cases.

PubMed

Osborne, B M; Robboy, S J

1983-11-15

Forty cases of ovarian lymphoma and two of extramedullary leukemia were examined with emphasis on histologic types correlated with age, modes of presentation, operative findings, including frequency of bilaterality and omental spread, clinical course following therapy, and problems in differential diagnosis. Although most cases were referred with diagnoses other than lymphoma (granulosa cell tumor or dysgerminoma, occasionally anaplastic tumor, Krukenberg tumor, or metastatic breast carcinoma), utilization of sections cut at 4 mu and stained with hematoxylin and eosin, or sections stained by the methyl green pyronine (MGP), naphthol-ASD esterase (NASD) or periodic acid-Schiff (PAS) methods helped bring out the lymphoid or hematopoietic nature of the cells. Sixteen patients were under 20 years of age. They had small noncleaved cell lymphoma (undifferentiated Burkitt's and non-Burkitt's, 10 cases), diffuse immunoblastic large cell lymphoma (4 cases), or acute granulocytic leukemia (2 cases). Twenty-six patients were 29 to 74 years of age and had diffuse large cell lymphoma (10 cases), diffuse immunoblastic large cell lymphoma (9 cases), follicular (nodular) lymphoma (6 cases) or small noncleaved cell lymphoma (1 case). Pain with an abdominal or pelvic mass was the most common presentation. Nine tumors were discovered during investigation of other gynecologic complaints. At laparotomy, the tumors in 55% of cases involved both ovaries, and in 64% also involved extragonadal sites (usually omentum, fallopian tubes, or lymph nodes). Seventeen patients had tumor affecting one ovary, seven of these without any evidence of extragonadal spread. Forty-two percent (15) of 37 patients with follow-up were alive after 2 years. Only nine patients survived more than 5 years; two subsequently died of lymphoma. Favorable prognostic features included: (1) FIGO stage IA; (2) unilateral ovarian involvement; (3) focal involvement of one ovary; and (4) follicular (nodular) lymphoma.

Highly expressed long non-coding RNA NNT-AS1 promotes cell proliferation and invasion through Wnt/β-catenin signaling pathway in cervical cancer.

PubMed

Hua, Fangfang; Liu, Shanshan; Zhu, Lihong; Ma, Ning; Jiang, Shan; Yang, Jun

2017-08-01

Cervical cancer is the most common gynecological malignancies in women worldwide. The previous study showed that lncRNA NNT-AS1 could play an important role in tumor development and metastasis of colorectal cancer. However, little is known about the function of NNT-AS1 in cervical cancer. The aim of this study was to investigate the expression profile of NNT-AS1 in cervical cancer and assess its possible molecular mechanism. Relative expression levels of NNT-AS1 in cervical cancer tissues were determined by qRT-PCR. The biologic functions of NNT-AS1 in cervical cancer were explored by MTT assay, transwell assay and flow cytometric analysis in vitro. The influence of NNT-AS1 on tumorigenesis was measured by mice xenograft model. In addition, we evaluated the activation of Wnt/β-catenin signaling pathway by luciferase assay and western blot. Our results showed that NNT-AS1 expression in cervical cancer tissues compared with adjacent non-tumor tissues the overexpression of NNT-AS1 was positively associated with advanced FIGO stage, lymph node metastasis, depth of cervical invasion and poorer overall survival. Function assays showed that NNT-AS1 inhibition could suppress cervical cancer cells proliferation and invasion ability in vitro as well as the activation of Wnt/β-catenin signaling pathway. In vivo mice xenograft model revealed that silencing NNT-AS1 could reduce tumor growth in nude mice. The results of the current study suggested that NNT-AS1 might play an important role in cervical carcinogenesis and might serve as a potentially therapeutic target and prognostic marker in the treatment of cervical cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study

PubMed Central

Pignata, Sandro; Ferrandina, Gabriella; Scarfone, Giovanna; Scollo, Paolo; Odicino, Franco; Cormio, Gennaro; Katsaros, Dionyssios; Villa, Antonella; Mereu, Liliana; Ghezzi, Fabio; Manzione, Luigi; Lauria, Rossella; Breda, Enrico; Alletti, Desiderio Gueli; Ballardini, Michela; Lombardi, Alessandra Vernaglia; Sorio, Roberto; Mangili, Giorgia; Priolo, Domenico; Magni, Giovanna; Morabito, Alessandro

2008-01-01

Background Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer. Methods The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000–2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible. Results Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056) and less advanced FIGO stage (p = 0.025). At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024). About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03). Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026), with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04). Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023). Conclusion This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed. PMID:18761742

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guy, Jean-Baptiste; Falk, Alexander T.; Auberdiac, Pierre

Introduction: For patients with cervical cancer, intensity-modulated radiation therapy (IMRT) improves target coverage and allows dose escalation while reducing the radiation dose to organs at risk (OARs). In this study, we compared dosimetric parameters among 3-dimensional conformal radiotherapy (3D-CRT), “step-and-shoot” IMRT, and volumetric intensity-modulated arc radiotherapy (VMAT) in a series of patients with cervical cancer receiving definitive radiotherapy. Computed tomography (CT) scans of 10 patients with histologically proven cervical cancer treated with definitive radiation therapy (RT) from December 2008 to March 2010 at our department were selected for this study. The gross tumor volume (GTV) and clinical target volume (CTV)more » were delineated following the guidelines of the Gyn IMRT consortium that included cervix, uterus, parametrial tissues, and the pelvic nodes including presacral. The median age was 57 years (range: 30 to 85 years). All 10 patients had squamous cell carcinoma with Federation of Gynecology and Obstetrics (FIGO) stage IB-IIIB. All patients were treated by VMAT. OAR doses were significantly reduced for plans with intensity-modulated technique compared with 3D-CRT except for the dose to the vagina. Between the 2 intensity-modulated techniques, significant difference was observed for the mean dose to the small intestine, to the benefit of VMAT (p < 0.001). There was no improvement in terms of OARs sparing for VMAT although there was a tendency for a slightly decreased average dose to the rectum: − 0.65 Gy but not significant (p = 0.07). The intensity modulation techniques have many advantages in terms of quality indexes, and particularly OAR sparing, compared with 3D-CRT. Following the ongoing technologic developments in modern radiotherapy, it is essential to evaluate the intensity-modulated techniques on prospective studies of a larger scale.« less

Transforming growth factor-beta and nitrates in epithelial ovarian cancer.

PubMed

Khalifa, A; Kassim, S K; Ahmed, M I; Fayed, S T

1999-12-01

The role of transforming growth factor-beta (TGF-beta) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-beta by enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-beta, nitrate, and SPF were significant among different groups (X2 = 12.01, P = 0.0025, X2 = 67.42, P = 0.000, X2 = 9.06, P = 0.011 respectively). Nitrate mean ranks were significant among different FIGO stages of the disease (X2 = 17.6, P = 0.000). A significant correlation was shown between TGF-beta, and nitrate levels in all tissues (r = 0.24, P = 0.01), as well as in malignant tissues (r = 0.3, P = 0.026). Cutoff values were determined for both TGF-beta (290 pg/mg protein), and nitrates (310 nmole/mg non protein nitrogenous substances). At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-beta had 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-beta above the cut-off had worse prognosis (X2 = 12.69, P = 0.004). The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-beta and NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-beta could be of prognostic significance.

Transforming Growth Factor-β and Nitrates in Epithelial Ovarian Cancer

PubMed Central

Khalifa, Ali; Kassim, Samar K.; Ahmed, Maha I.; Fayed, Salah T.

1999-01-01

The role of transforming growth factor-β (TGF-β) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-β by enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-β, nitrate, and SPF were significant among different groups (X2 = 12.01, P = 0.0025, X2 = 67.42, P = 0.000, X2 = 9.06, P = 0.011 respectively). Nitrate mean ranks were significant among different FIGO stages of the disease (X2 = 17.6, P = 0.000). A significant correlation was shown between TGF-â, and nitrate levels in all tissues (r = 0.24, P = 0.01), as well as in malignant tissues (r = 0.3, P = 0.026). Cutoff values were determined for both TGF-β (290 pg/mg protein), and nitrates (310 nmole/mg non protein nitrogenous substances). At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-β had 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-β above the cut-off had worse prognosis (X2 = 12.69, P = 0.004). The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-β and NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-β could be of prognostic significance. PMID:10689548

A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

PubMed

Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

2016-08-17

This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.

PubMed

Rafii, Saeed; Gourley, Charlie; Kumar, Rajiv; Geuna, Elena; Ern Ang, Joo; Rye, Tzyvia; Chen, Lee-May; Shapira-Frommer, Ronnie; Friedlander, Michael; Matulonis, Ursula; De Greve, Jacques; Oza, Amit M; Banerjee, Susana; Molife, L Rhoda; Gore, Martin E; Kaye, Stan B; Yap, Timothy A

2017-07-18

The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.

Long non-coding RNA taurine-upregulated gene 1 predicts unfavorable prognosis, promotes cells proliferation, and inhibits cells apoptosis in epithelial ovarian cancer.

PubMed

Li, Tong-Huai; Zhang, Jing-Jing; Liu, Shao-Xiao; Chen, Yan

2018-05-01

The aim of this study was to evaluate the correlation of long non-coding RNAs (lncRNAs) taurine-upregulated gene 1 (TUG1) with clinicopathological characteristics as well as overall survival (OS) in epithelial ovarian cancer (EOC) patients, and investigate its function in EOC cells proliferation and apoptosis in vitro.LncRNA TUG1 expressions were detected in tumor tissues and paired adjacent tissues obtained from 96 EOC patients. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor plasmids were transfected into SKOV3 cells. CKK-8, annexin V-FITC-propidium iodide, qPCR and western blot assays were performed to detect cells proliferation, cells apoptosis, RNA expression, and protein expression, respectively.LncRNA TUG1 expression was higher in tumor tissue compared to paired adjacent tissue (P < .001), and it was positively correlated with pathological grade (P = .022), tumor size (P = .011) and FIGO stage (P < .001). Kaplan-Meier curve showed that lncRNA TUG1 high expression was associated with worse OS (P = .003). Multivariate Cox analysis indicated that lncRNA TUG1 high expression (vs. low expression) (P = .035) was independently predictive factor for shorter OS. In vitro, cells proliferation was promoted after treatment with lncRNA TUG1 mimic and was suppressed after treatment with lncRNA TUG1 inhibitor. In addition, cells apoptosis rate was decreased in lncRNA TUG1 mimic group compared to NC1 mimic, and increased in lncRNA TUG1 inhibitor group compared to NC2 inhibitor.In conclusion, lncRNA TUG1 is positively correlated with advanced disease and poor prognosis, and it promotes cells proliferation and inhibits cells apoptosis in EOC cells.

The prognostic impact of cancer stem-like cell biomarker aldehyde dehydrogenase-1 (ALDH1) in ovarian cancer: A meta-analysis.

PubMed

Ruscito, Ilary; Darb-Esfahani, Silvia; Kulbe, Hagen; Bellati, Filippo; Zizzari, Ilaria Grazia; Rahimi Koshkaki, Hassan; Napoletano, Chiara; Caserta, Donatella; Rughetti, Aurelia; Kessler, Mirjana; Sehouli, Jalid; Nuti, Marianna; Braicu, Elena Ioana

2018-05-10

To investigate the association of cancer stem cell biomarker aldehyde dehydrogenase-1 (ALDH1) with ovarian cancer patients' prognosis and clinico-pathological characteristics. The electronic searches were performed in January 2018 through the databases PubMed, MEDLINE and Scopus by searching the terms: "ovarian cancer" AND "immunohistochemistry" AND ["aldehyde dehydrogenase-1" OR "ALDH1" OR "cancer stem cell"]. Studies evaluating the impact of ALDH1 expression on ovarian cancer survival and clinico-pathological variables were selected. 233 studies were retrieved. Thirteen studies including 1885 patients met all selection criteria. ALDH1-high expression was found to be significantly associated with poor 5-year OS (OR = 3.46; 95% CI: 1.61-7.42; P = 0.001, random effects model) and 5-year PFS (OR = 2.14; 95% CI: 1.11-4.13; P = 0.02, random effects model) in ovarian cancer patients. No correlation between ALDH1 expression and tumor histology (OR = 0.60; 95% CI: 0.36-1.02; P = 0.06, random effects model), FIGO Stage (OR = 0.65; 95% CI: 0.33-1.30; P = 0.22, random effects model), tumor grading (OR = 0.76; 95% CI: 0.40-1.45; P = 0.41, random effects model) lymph nodal status (OR = 2.05; 95% CI: 0.81-5.18; P = 0.13, random effects model) or patients' age at diagnosis (OR = 0.83; 95% CI: 0.54-1.29; P = 0.41, fixed effects model) was identified. Basing on the available evidence, this meta-analysis showed that high levels of ALDH1 expression correlate with worse OS and PFS in ovarian cancer patients. Copyright © 2018. Published by Elsevier Inc.

Stromal Fibroblasts Induce CCL20 through IL6/C/EBPβ to Support the Recruitment of Th17 Cells during Cervical Cancer Progression.

PubMed

Walch-Rückheim, Barbara; Mavrova, Russalina; Henning, Melanie; Vicinus, Benjamin; Kim, Yoo-Jin; Bohle, Rainer Maria; Juhasz-Böss, Ingolf; Solomayer, Erich-Franz; Smola, Sigrun

2015-12-15

Cervical cancer is a consequence of persistent infection with human papillomaviruses (HPV). Progression to malignancy is linked to an inflammatory microenvironment comprising T-helper-17 (Th17) cells, a T-cell subset with protumorigenic properties. Neoplastic cells express only low endogenous levels of the Th17 chemoattractant CCL20, and therefore, it is unclear how Th17 cells are recruited to the cervical cancer tissue. In this study, we demonstrate that CCL20 was predominantly expressed in the stroma of cervical squamous cell carcinomas in situ. This correlated with stromal infiltration of CD4(+)/IL17(+) cells and with advancing International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, we show that cervical cancer cells instructed primary cervical fibroblasts to produce high levels of CCL20 and to attract CD4/IL17/CCR6-positive cells, generated in vitro, in a CCL20/CCR6-dependent manner. Further mechanistic investigations identified cervical cancer cell-derived IL6 as an important mediator of paracrine CCL20 induction at the promoter, mRNA, and protein level in fibroblasts. CCL20 was upregulated through the recently described CCAAT/enhancer-binding protein β (C/EBPβ) pathway as shown with a dominant-negative version of C/EBPβ and through siRNA-mediated knockdown. In summary, our study defines a novel molecular mechanism by which cervical neoplastic cells shape their local microenvironment by instructing fibroblasts to support Th17 cell infiltration in a paracrine IL6/C/EBPβ-dependent manner. Th17 cells may in turn maintain chronic inflammation within high-grade cervical lesions to further promote cancer progression. ©2015 American Association for Cancer Research.

Prognostic significance of highly sulfated chondroitin sulfates in ovarian cancer defined by the single chain antibody GD3A11.

PubMed

van der Steen, Sophieke C H A; van Tilborg, Angela A G; Vallen, Myrtille J E; Bulten, Johan; van Kuppevelt, Toin H; Massuger, Leon F A G

2016-03-01

The extracellular matrix (ECM) of ovarian cancer may provide a number of potential biomarkers. Chondroitin sulfate (CS), a class of sulfated polysaccharides, is abundantly present in the ECM of ovarian cancer. Structural alterations of CS chains (i.e. sulfation pattern) have been demonstrated to play a role in cancer development and progression. In this study we investigate the potential of highly sulfated CS as a biomarker in ovarian cancer using the single chain antibody GD3A11 selected by the phage display technology. The specificity of the antibody was determined by an indirect ELISA. GD3A11 epitope expression was assessed by immunohistochemistry in healthy organs, benign and malignant ovarian tumors (N=359) and correlated to clinical parameters. The CHST15 gene, responsible for the biosynthesis of highly sulfated CS was evaluated for mutation and methylation status. The GD3A11 epitope was minimally expressed in normal organs. Intense expression was observed in the ECM of different ovarian cancer subtypes, in contrast to benign ovarian tumors. Expression was independent of tumor grade, FIGO stage, and the use chemotherapy. For the aggressive ovarian cancer phenotype, intense expression was identified as an independent predictor for poor prognosis. CHST15 gene analysis showed no mutations nor an altered methylation status. Specific highly sulfated CS motifs expressed in the tumoral ECM hold biomarker potential in ovarian cancer patients. These matrix motifs constitute a novel class of biomarkers with prognostic significance and may be instrumental for innovative diagnostic and therapeutic applications (e.g. targeted therapy) in management of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Nerve-sparing abdominal radical trachelectomy: a novel concept to preserve uterine branches of pelvic nerves.

PubMed

Kyo, Satoru; Mizumoto, Yasunari; Takakura, Masahiro; Nakamura, Mitsuhiro; Sato, Emi; Katagiri, Hiroshi; Ishikawa, Masako; Nakayama, Kentaro; Fujiwara, Hiroshi

2015-10-01

Nerve-sparing techniques to avoid bladder dysfunction in abdominal radical hysterectomy have been established during the past two decades, and they have been applied to radical trachelectomy. Although trachelectomy retains the uterine corpus, no report mentions the preservation of uterine branches of pelvic nerves. The aim of the present study was to introduce and discuss our unique concept for preserving them. Four cases with FIGO stage Ia2-Ib1 cervical cancer, in which preservation of uterine branches of the pelvic nerves was attempted, are presented. Operative procedures basically followed the previously reported standard approaches for nerve-sparing radical hysterectomy or trachelectomy, except for some points. Before resection of the sacrouterine ligament, the hypogastric nerve was first identified and translocated laterally. Subsequently, the uterine branches of the pelvic nerve were identified as a continuation of the hypogastric nerve and could be scooped with forceps by detachment of the surrounding connective tissues. Further detachment toward the uterine corpus enabled them to be completely separated from the cervix. This separation was extended up to the level of the junction of the upper and lower branches of the uterine artery. Thereafter, standard resection of the parametrium and paracolpium was performed, followed by cervical resection when it was confirmed that the isolated uterine branches of the pelvic nerves were safely translocated and preserved. There were no recurrences of cancer in these patients. Uterine branches of autonomic nerves can be safely preserved, and the procedure may be considered one of the nerve-sparing techniques for radical abdominal trachelectomy, which may hopefully improve the reproductive outcomes of this operation, although it needs to be evaluated with more patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prognostic and clinicopathological significance of Cacna2d1 expression in epithelial ovarian cancers: a retrospective study

PubMed Central

Yu, Dandan; Holm, Ruth; Goscinski, Mariusz Adam; Trope, Claes G; Nesland, Jahn M; Suo, Zhenhe

2016-01-01

Ovarian cancer is the most lethal gynecologic malignancy, in which cancer stem cells (CSC) have been reported to be the driving force of relapse and therapy-resistance. It is therefore important to explore CSC markers in ovarian cancer. This project aimed to explore the correlation between the expression of potential CSC maker Cacna2d1 and clinicopathological parameters in 238 epithelial ovarian cancer (EOC) samples. Immunohistochemically, positive Cacna2d1 expression was observed in 83.6% (199/238) of the EOC tumors, among which 107 tumors (44.9%) were highly positive and 92 (38.7%) tumors were weakly positive for the Cacna2d1 protein expression. Among the 158 serous carcinomas, the Cacna2d1 positivity was 148 (93.7%), in which 88 (55.7%) were highly positive, and 60 (38.0%) were weakly positive for the Cacna2d1 protein expression. Most strikingly, the Cacna2d1 was specifically expressed in the infiltration front areas of the EOC tumors. Statistical analyses showed that positive expression of Cacna2d1 was significantly associated with advanced FIGO stage (P<0.001), histological subtype (P=0.017) and tumor differentiation (P=0.015). Positive Cacna2d1 protein expression was significantly associated with poor overall survival (OS) and shorter progression free survival (PFS) in both total EOCs and serous carcinomas, although multivariate analyses did not reach statistical significance. In summary, our results suggest Cacna2d1 protein may play a crucial role in promoting aggressive EOC behavior and progression, and Cacna2d1 may serve as a novel predictive prognostic marker and a potential target for therapeutic intervention in EOCs. PMID:27725913

Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary.

PubMed

Ahmed, Ahmed Ashour; Etemadmoghadam, Dariush; Temple, Jillian; Lynch, Andy G; Riad, Mohamed; Sharma, Raghwa; Stewart, Colin; Fereday, Sian; Caldas, Carlos; Defazio, Anna; Bowtell, David; Brenton, James D

2010-05-01

Numerous studies have tested the association between TP53 mutations in ovarian cancer and prognosis but these have been consistently confounded by limitations in study design, methodology, and/or heterogeneity in the sample cohort. High-grade serous (HGS) carcinoma is the most clinically important histological subtype of ovarian cancer. As these tumours may arise from the ovary, Fallopian tube or peritoneum, they are collectively referred to as high-grade pelvic serous carcinoma (HGPSC). To identify the true prevalence of TP53 mutations in HGPSC, we sequenced exons 2-11 and intron-exon boundaries in tumour DNA from 145 patients. HGPSC cases were defined as having histological grade 2 or 3 and FIGO stage III or IV. Surprisingly, pathogenic TP53 mutations were identified in 96.7% (n = 119/123) of HGPSC cases. Molecular and pathological review of mutation-negative cases showed evidence of p53 dysfunction associated with copy number gain of MDM2 or MDM4, or indicated the exclusion of samples as being low-grade serous tumours or carcinoma of uncertain primary site. Overall, p53 dysfunction rate approached 100% of confirmed HGPSCs. No association between TP53 mutation and progression-free or overall survival was found. From this first comprehensive mapping of TP53 mutation rate in a homogeneous group of HGPSC patients, we conclude that mutant TP53 is a driver mutation in the pathogenesis of HGPSC cancers. Because TP53 mutation is almost invariably present in HGPSC, it is not of substantial prognostic or predictive significance. Copyright (c) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Long non-coding RNA FEZF1-AS1 is up-regulated and associated with poor prognosis in patients with cervical cancer.

PubMed

Zhang, H-H; Li, A-H

2018-06-01

Long noncoding RNA FEZF1-AS1 (FEZF1-AS1) has been showed to involve in a variety of cancers. However, its function and clinical significance in cervical cancer (CC) have not been investigated. The aim of this study was to explore the prognostic value of FEZF1-AS1 in CC patients. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression level of FEZF1-AS1 in CC specimens and adjacent normal cervical tissues. Association between FEZF1-AS1 expression and clinicopathological characteristics was analyzed x2-test. The Kaplan-Meier method was used to estimate survival curves, and the log-rank statistic was used to test the role of FEZF1-AS1 expression. The possibility of FEZF1-AS1 as a prognostic biomarker for CC was examined by Cox proportional hazard regression model. We found that FEZF1-AS1 expression levels were significantly higher in CC tissues compared with adjacent non-cancerous tissues (p < 0.01). High expressions of FEZF1-AS1 were significantly association with poorer histological grade (p = 0.004), positive distant metastasis (p = 0.002) and advanced FIGO stage (p = 0.001). Furthermore, patients with low FEZF1-AS1 expression lived shorter than those with high FEZF1-AS1 expression (Log-rank test, p < 0.0034). Cox regression analysis demonstrated that FEZF1-AS1 expression level was an independent prognostic factor for CC overall survival rates (p = 0.008). We firstly provided clinical evidence that FEZF1-AS1 may be a possible biomarker of poor prognosis in CC.

Role of zinc and α2macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma

PubMed Central

Mocchegiani, E; Ciavattini, A; Santarelli, L; Tibaldi, A; Muzzioli, M; Bonazzi, P; Giacconi, R; Fabris, N; Garzetti, G G

1999-01-01

Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. α2-Macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because α2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35–60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2–IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented α2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and α2-macroglobulin (r = 0.75, P< 0.01, r = 0.78, P< 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in α2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency. © 1999 Cancer Research Campaign PMID:9888464

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma

PubMed Central

Arakawa, Noriaki; Kobayashi, Hiroshi; Yonemoto, Naohiro; Masuishi, Yusuke; Ino, Yoko; Shigetomi, Hiroshi; Furukawa, Naoto; Ohtake, Norihisa; Miyagi, Yohei; Hirahara, Fumiki; Hirano, Hisashi; Miyagi, Etsuko

2016-01-01

Background There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. Methods Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. Results The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. Conclusions TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC. PMID:27798689

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.

PubMed

Arakawa, Noriaki; Kobayashi, Hiroshi; Yonemoto, Naohiro; Masuishi, Yusuke; Ino, Yoko; Shigetomi, Hiroshi; Furukawa, Naoto; Ohtake, Norihisa; Miyagi, Yohei; Hirahara, Fumiki; Hirano, Hisashi; Miyagi, Etsuko

2016-01-01

There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC.

Endometrial adenocarcinoma in a 13-year-old girl.

PubMed

Kim, Sung Mee; Shin, So Jin; Bae, Jin Gon; Kwon, Kun Young; Rhee, Jeong Ho

2016-03-01

Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature.

Perspectives on diagnostic strategies for hyperglycemia in pregnancy - Dealing with the barriers and challenges in South Asia.

PubMed

Kapur, Anil; Divakar, Hema; Seshiah, Veeraswamy

2018-02-02

Estimates indicate that south Asia accounts for over two fifths of the global burden of hyperglycemia in pregnancy (HIP) and the ongoing nutritional and epidemiological transition may make the situation worse. Given their higher risk, all women of south Asian decent require to be tested for HIP. With approximately 37 million births annually in the region requires that 37 million women be tested annually; thereby placing a huge burden on the fragile inadequately resourced health systems in the region with poor awareness and lack of trained manpower. Recommendation for testing must therefore be pragmatic, feasible, convenient and cost effective. Diabetes in pregnancy study group India (DIPSI) has proposed a simple testing protocol that is endorsed by the Indian National Guideline on GDM, and by the FIGO guideline on HIP for use in South Asia. This testing protocol has received widespread support in the region. Despite the many challenges it is encouraging to note that in the four large countries in the region - Bangladesh, India, Pakistan and Sri Lanka which account for over 80% of the estimated burden of HIP in south Asia, large scale credible programs have been initiated to address the identified barriers. Copyright © 2018. Published by Elsevier B.V.

Efficacy of ormeloxifene versus oral contraceptive in the management of abnormal uterine bleeding due to uterine leiomyoma.

PubMed

Kriplani, Alka; Srivastava, Astha; Kulshrestha, Vidushi; Kachhawa, Garima; Agarwal, Nutan; Bhatla, Neerja; Hari, Smriti

2016-12-01

To compare ormeloxifene with combined oral contraceptive (COC) in abnormal uterine bleeding (AUB) due to leiomyoma (AUB-L). Fifty women with AUB-L were randomized after informed consent and institute ethics clearance. Group I (n = 25) was given ormeloxifene (a SERM i.e. selective estrogen receptor modulator) 60 mg twice per week and group II (n = 25) was given COC (ethinyl estradiol 30 μg with desogestrel 150 μg) on days 1-21 for 6 months. Menstrual blood loss was assessed on pictorial blood loss assessment chart (PBAC) score and leiomyoma volume was assessed on ultrasound. Fibroids were classified according to FIGO-PALM-COEIN classification for AUB where leiomyomas were further sub-classified as types 0 to 8 according to their location. Follow up was done at 1, 3, 6 and 9 months. Mean PBAC score reduced by 81% with ormeloxifene (group I) compared with 43.8% for COC (group II). After 6 months, 18 patients (72%) in group I had PBAC score in the non-menorrhagic range (<100) compared with only two (8%) in group II. In group I, PBAC score in FIGO-PALM-COEIN leiomyoma types 2, 3, 4, 5, 6 reduced by 90.2%, 82.5%, 93.3%, 56.4% and 100%, respectively and 14 (56%) developed amenorrhea; compared with reduction of 64%, 27.5%, 25.9% in types 4, 5 and 6, respectively in group II. Dysmenorrhea visual analog scale score decreased in both groups. Mean leiomyoma volume increased in both groups: by 25.7% with ormeloxifene versus 16.9% with COC; only grade 2 leiomyoma in group I reduced by 44%. One patient in group II with grade 2 leiomyoma discontinued treatment at 3 months. Seven patients (28%) developed ovarian cyst in group I with no other major adverse effect in either group. Ormeloxifene with its convenient twice-weekly dosage schedule was effective in treating AUB-L, with 72% of patients responding to 6-month treatment compared with 8% with COC, even though leiomyoma volume increased insignificantly with both ormeloxifene and COCs. © 2016 Japan Society of Obstetrics and Gynecology.

Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

PubMed Central

Winter-Roach, Brett A; Kitchener, Henry C; Lawrie, Theresa A

2014-01-01

Background Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the precise role of this treatment in subgroups of women with differing prognoses needs to be defined. Objectives To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly to determine if clinical subgroups of differing prognosis based on histological sub-type, or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery. Search methods We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH). Selection criteria We selected randomised clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures. Data collection and analysis Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. We performed random-effects meta-analyses and subgroup analyses. Main results Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four trials were included in the meta-analyses and we considered them to be at a low risk of bias. Meta-analysis of five-year data from three trials indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (1008 women; hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.53 to 0.93). Likewise, meta-analysis of five-year data from four trials indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (1170 women; HR 0.67; 95% CI 0.53 to 0.84). The trials included in these meta-analyses gave consistent estimates of the effects of chemotherapy. In addition, these findings were robust over time (10-year PFS: two trials, 925 women; HR 0.67; 95% CI 0.54 to 0.84). Subgroup analysis suggested that women who had optimal surgical staging of their disease were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63 to 2.37; two trials, 234 women) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85; two trials, 772 women). One trial showed a benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95% CI 0.32 to 0.72) but not among those at low/medium risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these subgroup findings could be due to chance and should be interpreted with caution. Authors’ conclusions Adjuvant platinum-based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer. However, it may be withheld from women in whom there is well-differentiated encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively staged Ib, well or moderately differentiated (grade 1/2) disease. Others with unstaged early disease or those with poorly differentiated tumours should be offered chemotherapy. A pragmatic approach may be necessary in clinical settings where optimal staging is not normally performed/achieved. In such settings, adjuvant chemotherapy may be withheld from those with encapsulated stage Ia grade 1 serous and endometrioid carcinoma and offered to all others with early stage disease. PMID:22419298

Global efforts for effective training in fistula surgery.

PubMed

Elneil, Sohier

2015-10-01

Obstetric fistulas continue to be a problem in low- and middle-income nations, affecting women of childbearing age during pregnancy and labor and resulting in debilitating urinary and/or fecal incontinence. Historically, this predicament also affected women in high-income nations until the middle of the last century. This is not a "new world" crisis therefore, but simply one of economic and health development. In the last two decades, new global initiatives have been instituted to improve training and education in preventative and curative fistula treatment by developing a unified and competency-based learning tool by surgeons in the field in partnership with FIGO and its global partners. This modern approach to the management of a devastating condition can only serve to achieve the WHO objective of health security for women throughout their life span. Copyright © 2015. Published by Elsevier Ireland Ltd.

Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

NASA Astrophysics Data System (ADS)

Herrera, Higmar; Yañez, Elvia; Deras, Diana C.; Reyes, Francianella

2010-12-01

This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55±13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

Sentinel node detection in cervical cancer with (99m)Tc-phytate.

PubMed

Silva, Lucas B; Silva-Filho, Agnaldo L; Traiman, Paulo; Triginelli, Sérgio A; de Lima, Carla Flávia; Siqueira, Cristiano Ferrari; Barroso, Adelanir; Rossi, Telma Maria F F; Pedrosa, Moises Salgado; Miranda, Dairton; Melo, José Renan Cunha

2005-05-01

The aim of this study was to investigate the feasibility of sentinel lymph node (SLN) identification using radioisotopic lymphatic mapping with technetium-99 m-labeled phytate in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. Between July 2001 and February 2003, 56 patients with cervical cancer FIGO stage I (n = 53) or stage II (n = 3) underwent sentinel lymph node detection with preoperative lymphoscintigraphy ((99m)Tc-labeled phytate injected into the uterine cervix, at 3, 6, 9, and 12 o'clock, at a dose of 55-74 MBq in a volume of 0.8 ml) and intraoperative lymphatic mapping with a handheld gamma probe. Radical hysterectomy was aborted in three cases because parametrial invasion was found intraoperatively and we performed only sentinel node resection. The remaining 53 patients underwent radical hysterectomy with complete pelvic lymphadenectomy. Sentinel nodes were detected using a handheld gamma-probe and removed for pathological assessment during the abdominal radical hysterectomy and pelvic lymphadenectomy. One or more sentinel nodes were detected in 52 out of 56 eligible patients (92.8%). A total of 120 SLNs were detected by lymphoscintigraphy (mean 2.27 nodes per patient) and intraoperatively by gamma probe. Forty-four percent of SLNs were found in the external iliac area, 39% in the obturator region, 8.3% in interiliac region, and 6.7% in the common iliac area. Unilateral sentinel nodes were found in thirty-one patients (59%). The remaining 21 patients (41%) had bilateral sentinel nodes. Microscopic nodal metastases were confirmed in 17 (32%) cases. In 10 of these patients, only SLNs had metastases. The 98 sentinel nodes that were negative on hematoxylin and eosin were submitted to cytokeratin immunohistochemical analysis. Five (5.1%) micrometastases were identified with this technique. The sensitivity of the sentinel node was 82.3% (CI 95% = 56.6-96.2) and the negative predictive value was 92.1% (CI 95% = 78.6-98.3). The accuracy of sentinel node in predicting the lymph node status was 94.2%. Preoperative lymphoscintigraphy and intraoperative lymphatic mapping with (99m)Tc-labeled phytate are effective in identifying sentinel nodes in patients undergoing radical hysterectomy and to select women in whom lymph node dissection can be avoided.

Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the Arbeitsgemeinschaft Gynäkologische Onkologie CaRE-1 multicenter study.

PubMed

Woelber, Linn; Griebel, Lis-Femke; Eulenburg, Christine; Sehouli, Jalid; Jueckstock, Julia; Hilpert, Felix; de Gregorio, Nikolaus; Hasenburg, Annette; Ignatov, Atanas; Hillemanns, Peter; Fuerst, Sophie; Strauss, Hans-Georg; Baumann, Klaus H; Thiel, Falk C; Mustea, Alexander; Meier, Werner; Harter, Philipp; Wimberger, Pauline; Hanker, Lars Christian; Schmalfeldt, Barbara; Canzler, Ulrich; Fehm, Tanja; Luyten, Alexander; Hellriegel, Martin; Kosse, Jens; Heiss, Christoph; Hantschmann, Peer; Mallmann, Peter; Tanner, Berno; Pfisterer, Jacobus; Richter, Barbara; Neuser, Petra; Mahner, Sven

2016-12-01

A tumour-free pathological resection margin of ≥8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer. AGO-CaRE-1 is a large retrospective study. Patients (n = 1618) with vulvar cancer ≥ FIGO stage IB treated at 29 German gynecologic-cancer-centres 1998-2008 were included. This subgroup analysis focuses on solely surgically treated node-negative patients with complete tumour resection (n = 289). Of the 289 analysed patients, 141 (48.8%) had pT1b, 140 (48.4%) pT2 and 8 (2.8%) pT3 tumours. One hundred twenty-five (43.3%) underwent complete vulvectomy, 127 (43.9%) partial vulvectomy and 37 (12.8%) radical local excision. The median minimal resection margin was 5 mm (1 mm-33 mm); all patients received groin staging, in 86.5% with full dissection. Median follow-up was 35.1 months. 46 (15.9%) patients developed recurrence, thereof 34 (11.8%) at the vulva, after a median of 18.3 months. Vulvar recurrence rates were 12.6% in patients with a margin <8 mm and 10.2% in patients with a margin ≥8 mm. When analysed as a continuous variable, the margin distance had no statistically significant impact on local recurrence (HR per mm increase: 0.930, 95% CI: 0.849-1.020; p = 0.125). Multivariate analyses did also not reveal a significant association between the margin and local recurrence neither when analysed as continuous variable nor categorically based on the 8 mm cutoff. Results were consistent when looking at disease-free-survival and time-to-recurrence at any site (HR per mm increase: 0.949, 95% CI: 0.864-1.041; p = 0.267). The need for a minimal margin of 8 mm could not be confirmed in the large and homogeneous node-negative cohort of the AGO-CaRE database. Copyright © 2016 Elsevier Ltd. All rights reserved.

MRI-Guided High–Dose-Rate Intracavitary Brachytherapy for Treatment of Cervical Cancer: The University of Pittsburgh Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gill, Beant S.; Kim, Hayeon; Houser, Christopher J.

2015-03-01

Purpose: Image-based brachytherapy is increasingly used for gynecologic malignancies. We report early outcomes of magnetic resonance imaging (MRI)-guided brachytherapy. Methods and Materials: Consecutive patient cases with FIGO stage IB1 to IVA cervical cancer treated at a single institution were retrospectively reviewed. All patients received concurrent cisplatin with external beam radiation therapy along with interdigitated high–dose-rate intracavitary brachytherapy. Computed tomography or MRI was completed after each application, the latter acquired for at least 1 fraction. High-risk clinical target volume (HRCTV) and organs at risk were identified by Groupe Européen de Curiethérapie and European SocieTy for Radiotherapy and Oncology guidelines. Doses weremore » converted to equivalent 2-Gy doses (EQD{sub 2}) with planned HRCTV doses of 75 to 85 Gy. Results: From 2007 to 2013, 128 patients, median 52 years of age, were treated. Predominant characteristics included stage IIB disease (58.6%) with a median tumor size of 5 cm, squamous histology (82.8%), and no radiographic nodal involvement (53.1%). Most patients (67.2%) received intensity modulated radiation therapy (IMRT) at a median dose of 45 Gy, followed by a median brachytherapy dose of 27.5 Gy (range, 25-30 Gy) in 5 fractions. At a median follow up of 24.4 months (range, 2.1-77.2 months), estimated 2-year local control, disease-free survival, and cancer-specific survival rates were 91.6%, 81.8%, and 87.6%, respectively. Predictors of local failure included adenocarcinoma histology (P<.01) and clinical response at 3 months (P<.01). Among the adenocarcinoma subset, receiving HRCTV D{sub 90} EQD{sub 2} ≥84 Gy was associated with improved local control (2-year local control rate 100% vs 54.5%, P=.03). Grade 3 or greater gastrointestinal or genitourinary late toxicity occurred at a 2-year actuarial rate of 0.9%. Conclusions: This study constitutes one of the largest reported series of MRI-guided brachytherapy in North America, demonstrating excellent local control with acceptable morbidity. Dose escalation may be warranted when feasible for adenocarcinomas to offset the risk of local failure.« less

A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma: Preliminary Results of RTOG 0417

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schefter, Tracey E., E-mail: tracey.schefter@ucdenver.edu; Winter, Kathryn; Kwon, Janice S.

Purpose: Concurrent cisplatin-based chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. RTOG 0417 was a Phase II study exploring the safety and efficacy of the addition of bevacizumab to standard CRT. Methods and Materials: Eligible patients with bulky tumors (Stage IB-IIIB) were treated with once-weekly cisplatin (40 mg/m{sup 2}) chemotherapy and standard pelvic radiotherapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for three cycles. Treatment-related serious adverse event (SAE) and other adverse event (AE) rates within the first 90 days from treatment start were determined. Treatment-related SAEs were defined as any Grademore » {>=}4 vaginal bleeding or thrombotic event or Grade {>=}3 arterial event, gastrointestinal (GI) bleeding, or bowel/bladder perforation, or any Grade 5 treatment-related death. Treatment-related AEs included all SAEs and Grade 3 or 4 GI toxicity persisting for >2 weeks despite medical intervention, Grade 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia, Grade 3 or 4 other hematologic toxicity, and Grade 3 or 4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs. All AEs were scored using the National Cancer Institute Common Terminology Criteria (CTCAE) v 3.0 (MedDRA version 6.0). Results: A total of 60 patients from 28 institutions were enrolled between 2006 and 2009, and of these, 49 patients were evaluable. The median follow-up was 12.4 months (range, 4.6-31.4 months).The median age was 45 years (range, 22-80 years). Most patients had FIGO Stage IIB (63%) and were of Zubrod performance status of 0 (67%). 80% of cases were squamous. There were no treatment-related SAEs. There were 15 (31%) protocol-specified treatment-related AEs within 90 days of treatment start; the most common were hematologic (12/15; 80%). 18 (37%) occurred during treatment or follow-up at any time. 37 of the 49 patients (76%) had cisplatin and bevacizumab administered per protocol, and 46 of the 49 (94%) had both external beam and brachytherapy administered per protocol or with acceptable variation. Conclusion: Bevacizumab in addition to standard pelvic chemoradiotherapy for locally advanced cervical cancer is feasible and safe with respect to the protocol-specified treatment-related SAEs and AEs.« less

SU-F-19A-12: Split-Ring Applicator with Interstitial Needle for Improved Volumetric Coverage in HDR Brachytherapy for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sherertz, T; Ellis, R; Colussi, V

2014-06-15

Purpose: To evaluate volumetric coverage of a Mick Radionuclear titanium Split-Ring applicator (SRA) with/without interstitial needle compared to an intracavitary Vienna applicator (VA), interstitial-intracavitary VA, and intracavitary ring and tandem applicator (RTA). Methods: A 57 year-old female with FIGO stage IIB cervical carcinoma was treated following chemoradiotherapy (45Gy pelvic and 5.4Gy parametrial boost) with highdose- rate (HDR) brachytherapy to 30Gy in 5 fractions using a SRA. A single interstitial needle was placed using the Ellis Interstitial Cap for the final three fractions to increase coverage of left-sided gross residual disease identified on 3T-MRI. High-risk (HR) clinical target volume (CTV) andmore » intermediate-risk (IR) CTV were defined using axial T2-weighted 2D and 3D MRI sequences (Philips PET/MRI unit). Organs-at-risks (OARs) were delineated on CT. Oncentra planning system was used for treatment optimization satisfying GEC-ESTRO guidelines for target coverage and OAR constraints. Retrospectively, treatment plans (additional 20 plans) were simulated using intracavitary SRA (without needle), intracavitary VA (without needle), interstitial-intracavitary VA, and intracavitary RTA with this same patient case. Plans were optimized for each fraction to maintain coverage to HR-CTV. Results: Interstitial-intracavitary SRA achieved the following combined coverage for external radiation and brachytherapy (EQD2): D90 HR-CTV =94.6Gy; Bladder-2cc =88.9Gy; Rectum-2cc =65.1Gy; Sigmoid-2cc =48.9Gy; Left vaginal wall (VW) =103Gy, Right VW =99.2Gy. Interstitial-intracavitary VA was able to achieve identical D90 HR-CTV =94.6Gy, yet Bladder-2cc =91.9Gy (exceeding GEC-ESTRO recommendations of 2cc<90Gy) and Left VW =120.8Gy and Right VW =115.5Gy. Neither the SRA nor VA without interstitial needle could cover HR-CTV adequately without exceeding dose to Bladder-2cc. Conventional RTA was unable to achieve target coverage for the HR-CTV >80Gy without severely overdosing OARs. Conclusion: The Ellis Interstitial Cap for the SRA offered superior dosimetric coverage as compared to the interstitialintracavitary VA. This represents the first reported use for this devise, and further investigation is warranted.« less

Contribution of the Central American and Caribbean obstetrics and gynecology societies to the prevention of unsafe abortion in the region.

PubMed

de Gil, Marina Padilla

2014-07-01

Unsafe abortion is a very important public health issue in the Central America and Caribbean region, where the use of modern contraceptive methods remains low and the restrictive legal framework reduces access to safe abortion. The International Federation of Gynecology and Obstetrics (FIGO) Initiative for the Prevention of Unsafe Abortion and its Consequences is contributing toward resolving this problem by strengthening collaboration between medical societies, representatives of each country's Ministry of Health, and local and international agencies. In the 8 countries that decided to join this initiative in 2008, progress has been achieved in improving access to modern contraceptive methods, increasing the use of manual vacuum aspiration and misoprostol, and updating guidelines on postabortion care. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrera, Higmar; Yanez, Elvia; Deras, Diana C.

2010-12-07

This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55{+-}13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher agemore » (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).« less

Proposal of a novel system for the staging of thymic epithelial tumors.

PubMed

Bedini, Amedeo Vittorio; Andreani, Stefano Michele; Tavecchio, Luca; Fabbri, Alessandra; Giardini, Roberto; Camerini, Tiziana; Bufalino, Rosaria; Morabito, Alberto; Rosai, Juan

2005-12-01

We designed and assessed a new TNM staging system (herein called the INT [Istituto Nazionale Tumori] system) for thymic epithelial tumors in order to overcome the perceived drawbacks of Masaoka's system, which represents the current standard. In all, 123 cases were evaluated. The histologic types according to the World Health Organization (WHO) classification were as follows: subtype A: 5 cases; AB: 40; B1: 16; B2: 29; B3: 16; and C: 17 cases. There were 45 Masaoka's stage I, 33 stage II, 26 stage III, and 19 stage IV cases. A total of 11 INT definitions were grouped into three stages: locally restricted disease (75 cases), which included Masaoka's stage I and selected stage II cases (no pleural invasion); locally advanced disease (37 cases), which included Masaoka's stage III cases plus those staged II owing to pleural invasion and those staged IV owing to intrathoracic nodal or limited pleuropericardial involvement; and systemic disease (11 cases), which included the remaining Masaoka's stage IV cases. Completeness of resection, WHO types, and both staging systems were significant prognostic factors (p < 0.0001) on univariate analysis. The 95-month progression-free survival rates according to Masaoka's system were stage I: 100%; II: 93.6%; III: 46.3%; and IV: 23.2%. The INT system corresponding figures were as follows: locally restricted disease: 98.6%; locally advanced disease: 46.9%; and systemic disease: 11.7%. The INT system was the prognostic factor with the greatest impact (p = 0.0218) on multivariate analysis (Masaoka's system: p = 0.2012; completeness of resection: p = 0.6855; histology: p = 0.9386). The INT system allows finer disease descriptions than Masaoka's system, resulting in a stage grouping with higher prognostic distinctiveness.

Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franckena, Martine; Stalpers, Lukas J.A.; Koper, Peter C.M.

2008-03-15

Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a medianmore » total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.« less

Efficacy of PET/CT to exclude leiomyoma in patients with lesions suspicious for uterine sarcoma on MRI.

PubMed

Kusunoki, Soshi; Terao, Yasuhisa; Ujihira, Takafumi; Fujino, Kazunari; Kaneda, Hiroshi; Kimura, Miki; Ota, Tsuyoshi; Takeda, Satoru

2017-08-01

To analyze the efficacy of positron emission tomography/computed tomography (PET/CT) for the diagnosis of uterine sarcoma. Thirty-four patients evaluated between January 2010 and March 2015 were retrospectively enrolled. All patients in whom uterine sarcoma was suspected based on contrast-enhanced magnetic resonance imaging (MRI) findings (heterogeneous, high signal intensity on T2-weighted images and/or high intensity on T1-weighted images) underwent PET/CT for further assessment. Patients were divided into 2 groups based on postoperative pathological findings: uterine sarcoma (n = 15) and leiomyoma (n = 19). The maximum standardized uptake value (SUVmax) of all lesions was measured using PET/CT; we calculated the optimal cutoff value for diagnosing sarcoma. The median SUVmax for uterine sarcoma and leiomyoma was 12 and 4.1, respectively; these values were significantly different. An SUVmax of greater than 7.5 was able to exclude leiomyoma with 80.8% sensitivity and 100% specificity (area under the curve, 95.3%). A cutoff SUVmax of 7.5 yields 100% specificity, and a cutoff SUVmax of 4.4 yields a 100% negative predictive value (NPV). The combination of PET/CT and lactate dehydrogenase (LDH) levels had a sensitivity of 86.6%, specificity of 100%, positive predictive value of 100%, and an NPV of 90.4%. No relation between histopathology or International Federation of Gynecology and Obstetrics (FIGO) stage and 18-fluoro-2-deoxy-d-glucose uptake value on PET/CT was seen. The surgical outcome trended toward a correlation with the SUVmax, although this was not statistically significant. In patients with MRI findings consistent with either uterine sarcoma or leiomyoma, PET/CT can decrease the false-positive rate by setting an optimal cutoff SUVmax of 7.5. Using this cutoff can avoid unnecessary surgery. Copyright © 2017. Published by Elsevier B.V.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Altazi, B; Fernandez, D; Zhang, G

Purpose: Radiomics have shown potential for predicting treatment outcomes in several body sites. This study investigated the correlation between PET Radiomics features and treatment response of cervical cancer outcomes. Methods: our dataset consisted of a cohort of 79 patients diagnosed with cervical cancer, FIGO stage IB-IVA, age range 25–86 years, (median age at diagnosis: 50 years) all treated between: 2009–14 with external beam radiation therapy to a dose range between: 45–50.4 Gy (median= 45 Gy), concurrent cisplatin chemotherapy and MRI-based brachytherapy to a dose of 20–30 Gy (median= 28 Gy). Metabolic Tumor Volume (MTV) in patient’s primary site was delineatedmore » on pretreatment PET/CT by two board certified Radiation Oncologists. The features extracted from each patient’s volume were: 26 Co-occurrence matrix (COM) Feature, 11 Run-Length Matrix (RLM), 11 Gray Level Size Zone Matrix (GLSZM) and 33 Intensity-based features (IBF). The treatment outcome was divided based on the last follow up status into three classes: No Evidence of Disease (NED), Alive with Disease (AWD) and Dead of Disease (DOD). The ability for the radiomics features to differentiate between the 3 treatments outcome categories were assessed by One-Way ANOVA test with p-value < 0.05 was to be statistically significant. The results from the analysis were compared with the ones obtained previously for standard Uptake Value (SUV). Results: Based on patients last clinical follow-up; 52 showed NED, 17 AWD and 10 DOD. Radiomics Features were able to classify the patients based on their treatment response. A parallel analysis was done for SUV measurements for comparison. Conclusion: Radiomics features were able to differentiate between the three different classes of treatment outcomes. However, most of the features were only able to differentiate between NED and DOD class. Also, The ability or radiomics features to differentiate types of response were more significant than SUV.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Altazi, B; Fernandez, D; Zhang, G

Purpose: Site-specific investigations of the role of Radiomics in cancer diagnosis and therapy are needed. We report of the reproducibility of quantitative image features over different discrete voxel levels in PET/CT images of cervical cancer. Methods: Our dataset consisted of the pretreatment PET/CT scans from a cohort of 76 patients diagnosed with cervical cancer, FIGO stage IB-IVA, age range 31–76 years, treated with external beam radiation therapy to a dose range between 45–50.4 Gy (median dose: 45 Gy), concurrent cisplatin chemotherapy and MRI-based Brachytherapy to a dose of 20–30 Gy (median total dose: 28 Gy). Two board certified radiation oncologistsmore » delineated Metabolic Tumor volume (MTV) for each patient. Radiomics features were extracted based on 32, 64, 128 and 256 discretization levels (DL). The 64 level was chosen to be the reference DL. Features were calculated based on Co-occurrence (COM), Gray Level Size Zone (GLSZM) and Run-Length (RLM) matrices. Mean Percentage Differences (Δ) of features for discrete levels were determined. Normality distribution of Δ was tested using Kolomogorov - Smirnov test. Bland-Altman test was used to investigate differences between feature values measured on different DL. The mean, standard deviation and upper/lower value limits for each pair of DL were calculated. Interclass Correlation Coefficient (ICC) analysis was performed to examine the reliability of repeated measures within the context of the test re-test format. Results: 3 global and 5 regional features out of 48 features showed distribution not significantly different from a normal one. The reproducible features passed the normality test. Only 5 reproducible results were reliable, ICC range 0.7 – 0.99. Conclusion: Most of the radiomics features tested showed sensitivity to voxel level discretization between (32 – 256). Only 4 GLSZM, 3 COM and 1 RLM showed insensitivity towards mentioned discrete levels.« less

PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway.

PubMed

Shu, Xiang-Rong; Wu, Jing; Sun, He; Chi, Li-Qun; Wang, Jin-Huan

2015-09-28

Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options. This study was designed to explore the potential prognosis value of p21-activated kinase (PAK)-4 in cervical cancer, via the Kaplan-Meier analysis, log-rank test and Cox regression analysis, and then to investigate the regulatory role of PAK4 in the cisplatin resistance in cervical cancer cells, via the strategies of both PAK4 overexpression and PAK4 knockout. It was demonstrated that PAK4 was upregulated in cervical cancer tissues, in an association with the cancer's malignance variables such as FIGO stage, lymph node or distant metastasis and the poor histological grade. The high PAK4 expression was also independently associated with poor prognosis to cervical cancer patients. Moreover, PAK4 confers cisplatin resistance in cervical cancer Hela or Caski cells. In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance. And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells. This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression. Moreover, our study has indicated that PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. Thus, our study indicates PAK4 as a promising marker for cervical cancer treatment.

Small cell carcinoma of the gynecologic tract: a multifaceted spectrum of lesions.

PubMed

Atienza-Amores, Maria; Guerini-Rocco, Elena; Soslow, Robert A; Park, Kay J; Weigelt, Britta

2014-08-01

Small cell carcinoma (SmCC) of the female genital tract constitutes a diagnostic and clinical challenge given its rarity and the lack of standardized therapeutic approaches. Here we review the morphological, clinical and molecular features of gynecologic SmCCs and discuss potential areas for future research. Data for this review article were identified by searches of PubMed, EMBASE and the Internet using the search terms "small cell carcinoma" or "neuroendocrine carcinoma" and "gynecologic", "uterine cervix", "cervix", "uterus", "endometrium", "ovary", "vagina", "fallopian tube" or "vulva", and research articles published in English between 1972 and February 2014 were included. SmCCs arising from different organs within the gynecologic tract share the same histopathologic characteristics, which closely resemble those of small cell lung carcinoma. The expression of at least one immunohistochemical neuroendocrine marker is a common finding. The uterine cervix is the most frequent site of SmCC in the female genital tract. HPV infection seems to play a role in the development of cervical SmCC but not in cancers of other gynecologic sites. FIGO stage is an established prognostic factor, in particular in SCCs of the cervix. Irrespective of the site, SmCCs of the gynecologic tract display an aggressive clinical behavior with few reported long-term survivors. The therapeutic management includes surgery, radiotherapy and chemotherapy. Despite the potential differences in etiology and risk factors, SmCCs from different sites of the gynecologic tract have similar morphologic appearances and clinical behavior. Recent genomic analyses of small cell carcinoma of the lung have revealed potential driver genomic alterations. We posit that the comprehensive genomic characterization of gynecologic SmCCs may lead to the identification of markers that result in an improvement of diagnostic reproducibility of SmCCs of the gynecologic tract, and of molecular aberrations that may be exploited therapeutically in subgroups of the disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of outcomes for MR-guided versus CT-guided high-dose-rate interstitial brachytherapy in women with locally advanced carcinoma of the cervix.

PubMed

Kamran, Sophia C; Manuel, Matthias M; Cho, Linda P; Damato, Antonio L; Schmidt, Ehud J; Tempany, Clare; Cormack, Robert A; Viswanathan, Akila N

2017-05-01

The purpose was to compare local control (LC), overall survival (OS) and dose to the organs at risk (OAR) in women with locally advanced cervical cancer treated with MR-guided versus CT-guided interstitial brachytherapy (BT). 56 patients (29 MR, 27 CT) were treated with high-dose-rate (HDR) interstitial BT between 2005-2015. The MR patients had been prospectively enrolled on a Phase II clinical trial. Data were analyzed using Kaplan-Meier (K-M) and Cox proportional hazards statistical modeling in JMP® & R®. Median follow-up time was 19.7months (MR group) and 18.4months (CT group). There were no statistically significant differences in patient age at diagnosis, histology, percent with tumor size >4cm, grade, FIGO stage or lymph node involvement between the groups. Patients in the MR group had more lymphovascular involvement compared to patients in the CT group (p<0.01). When evaluating plans generated, there were no statistically significant differences in median cumulative dose to the high-risk clinical target volume or the OAR. 2-year K-M LC rates for MR-based and CT-based treatments were 96% and 87%, respectively (log-rank p=0.65). At 2years, OS was significantly better in the MR-guided cohort (84% vs. 56%, p=0.036). On multivariate analysis, squamous histology was associated with longer OS (HR 0.23, 95% CI 0.07-0.72) in a model with MR BT (HR 0.35, 95% CI 0.08-1.18). There was no difference in toxicities between CT and MR BT. In this population of locally advanced cervical-cancer patients, MR-guided HDR BT resulted in estimated 96% 2-year local control and excellent survival and toxicity rates. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of outcomes for MR-guided versus CT-guided high-dose-rate interstitial brachytherapy in women with locally advanced carcinoma of the cervix

PubMed Central

Kamran, Sophia C.; Manuel, Matthias M.; Cho, Linda P.; Damato, Antonio L.; Schmidt, Ehud J.; Tempany, Clare; Cormack, Robert A.; Viswanathan, Akila N.

2017-01-01

Objective The purpose was to compare local control (LC), overall survival (OS) and dose to the organs at risk (OAR) in women with locally advanced cervical cancer treated with MR-guided versus CT-guided interstitial brachytherapy (BT). Methods 56 patients (29 MR, 27 CT) were treated with high-dose-rate (HDR) interstitial BT between 2005–2015. The MR patients had been prospectively enrolled on a Phase II clinical trial. Data were analyzed using Kaplan-Meier (K-M) and Cox proportional hazards statistical modeling in JMP® & R®. Results Median follow-up time was 19.7 months (MR group) and 18.4 months (CT group). There were no statistically significant differences in patient age at diagnosis, histology, percent with tumor size >4 cm, grade, FIGO stage or lymph node involvement between the groups. Patients in the MR group had more lymphovascular involvement compared to patients in the CT group (p<0.01). When evaluating plans generated, there were no statistically significant differences in median cumulative dose to the high-risk clinical target volume or the OAR. 2-year K-M LC rates for MR-based and CT-based treatments were 96% and 87%, respectively (log-rank p=0.65). At 2 years, OS was significantly better in the MR-guided cohort (84% vs. 56%, p=0.036). On multivariate analysis, squamous histology was associated with longer OS (HR 0.23, 95% CI 0.07–0.72) in a model with MR BT (HR 0.35, 95% CI 0.08–1.18). Conclusion In this population of locally advanced cervical-cancer patients, MR-guided HDR BT resulted in estimated 96% 2-year local control and excellent early survival rates. Squamous cell histology was the most significant predictor for survival. PMID:28318644

Imaging in gynecological disease (9): clinical and ultrasound characteristics of tubal cancer.

PubMed

Ludovisi, M; De Blasis, I; Virgilio, B; Fischerova, D; Franchi, D; Pascual, M A; Savelli, L; Epstein, E; Van Holsbeke, C; Guerriero, S; Czekierdowski, A; Zannoni, G; Scambia, G; Jurkovic, D; Rossi, A; Timmerman, D; Valentin, L; Testa, A C

2014-03-01

To describe clinical history and ultrasound findings in patients with tubal carcinoma. Patients with a histological diagnosis of tubal cancer who had undergone preoperative ultrasound examination were identified from the databases of 13 ultrasound centers. The tumors were described by the principal investigator at each contributing center on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, three authors reviewed together all available digital ultrasound images and described them using subjective evaluation of gray-scale and color Doppler ultrasound findings. We identified 79 women with a histological diagnosis of primary tubal cancer, 70 of whom (89%) had serous carcinomas and 46 (58%) of whom presented at FIGO stage III. Forty-nine (62%) women were asymptomatic (incidental finding), whilst the remaining 30 complained of abdominal bloating or pain. Fifty-three (67%) tumors were described as solid at ultrasound examination, 14 (18%) as multilocular solid, 10 (13%) as unilocular solid and two (3%) as unilocular. No tumor was described as a multilocular mass. Most tumors (70/79, 89%) were moderately or very well vascularized on color or power Doppler ultrasound. Normal ovarian tissue was identified adjacent to the tumor in 51% (39/77) of cases. Three types of ultrasound appearance were identified as being typical of tubal carcinoma using pattern recognition: a sausage-shaped cystic structure with solid tissue protruding into it like a papillary projection (11/62, 18%); a sausage-shaped cystic structure with a large solid component filling part of the cyst cavity (13/62, 21%); an ovoid or oblong completely solid mass (36/62, 58%). A well vascularized ovoid or sausage-shaped structure, either completely solid or with large solid component(s) in the pelvis, should raise the suspicion of tubal cancer, especially if normal ovarian tissue is seen adjacent to it. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

STAR and AKR1B10 are down-regulated in high-grade endometrial cancer.

PubMed

Sinreih, Maša; Štupar, Saša; Čemažar, Luka; Verdenik, Ivan; Frković Grazio, Snježana; Smrkolj, Špela; Rižner, Tea Lanišnik

2017-07-01

Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential of STAR and AKR1B10 as prognostic biomarkers, which calls for further validation at the protein level. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection of CCNE1/URI (19q12) amplification by in situ hybridisation is common in high grade and type II endometrial cancer

PubMed Central

Noske, Aurelia; Brandt, Simone; Valtcheva, Nadejda; Wagner, Ulrich; Zhong, Qing; Bellini, Elisa; Fink, Daniel; Obermann, Ellen C.; Moch, Holger; Wild, Peter J.

2017-01-01

One TCGA subgroup of endometrial cancer (EC) is characterised by extensive genomic DNA copy number alterations. CCNE1 located at 19q12 is frequently amplified in EC and a target for anti-cancer therapy. The relevance of URI, also located at 19q12, is unknown. To evaluate the prevalence of 19q12 (CCNE1/URI) in EC, we investigated different histologic types by in situ hybridisation (ISH) and copy number assay. We applied a previously established 19q12 ISH for the detection of CCNE1/URI copy numbers in EC (n = 270) using conventional bright field microscopy. In a subset (n = 21), 19q12 amplification status was validated by OncoScan assay. Manual ISH was controlled by a recently developed computational ISHProfiler algorithm. Associations of 19q12 status with Cyclin E1, URI and p53 expression, and clinico-pathological parameters were tested. Amplification of 19q12 (CCNE1/URI) was found in 10.4% (28/270) and was significantly associated with type II EC (high grade and non-endometrioid; p < 0.0001), advanced FIGO stage (p = 0.001), high Cyclin E1 expression (p = 0.008) and aberrant p53 expression (p = 0.04). 19q12 ISH data were confirmed by OncoScan and computational ISHProfiler techniques. The 19q12 in situ hybridisation is a feasible and robust biomarker assay in molecular pathology. Amplification of CCNE1/URI predominantly occurred in type II endometrial cancer. Prospective clinical trials are warranted to assess the utility of combined 19q12 amplification and Cyclin E1/URI protein expression analysis for the prediction of therapeutic response to chemotherapy and/or cyclin-dependent kinase inhibitors in patients with endometrial cancer. PMID:27582547

Decreased expression of pyruvate dehydrogenase A1 predicts an unfavorable prognosis in ovarian carcinoma.

PubMed

Li, Yaqing; Huang, Ruixia; Li, Xiaoli; Li, Xiaoran; Yu, Dandan; Zhang, Mingzhi; Wen, Jianguo; Goscinski, Mariusz Adam; Trope, Claes G; Nesland, Jahn M; Suo, Zhenhe

2016-01-01

Pyruvate dehydrogenase A1 (PDHA1) serves as a gate-keeper enzyme link between glycolysis and the mitochondrial citric acid cycle. The inhibition of PDHA1 in cancer cells can result in an increased Warburg effect and a more aggressive phenotype in cancer cells. This study was conducted to investigate the expression of PDHA1 in ovarian cancer and the correlation between PDHA1 expression and the prognosis of patients. The PDHA1 protein expression in 3 ovarian cancer cell lines (OVCAR-3, SKOV-3 and ES-2) and 248 surgically removed ovarian carcinoma samples was immunocytochemically examined. Statistical analyses were performed to evaluate the correlations between PDHA1 expression and the clinicopathological characteristics of the patients as well as the predictive value of PDHA1. The results showed the presence of variable expression of PDHA1 in the three ovarian cancer cell lines. Of the 248 ovarian cancer tissue specimens, 45 cases (18.1%) were negative in tumor cells for PDHA1, 162 cases (65.3%) displayed a low expression level, and 41 cases (16.5%) had a relatively high PDHA1 staining. The expression of PDHA1 was associated with the histological subtype ( P =0.004) and FIGO stage ( P =0.002). The median OS time in the PDHA1 negative group, low expression group and high expression group were 0.939 years, 1.443 years and 9.900 years, respectively. The median PFS time in the above three groups were 0.287 years, 0.586 years and 9.900 years, respectively. Furthermore, the high expression of PDHA1 in ovarian carcinoma cells was significantly associated with better OS and PFS by statistical analyses. Multivariate analyses showed that PDHA1 expression was also an independent prognostic factor for higher OS in ovarian cancer patients (HR=0.705, 95% CI 0.541-0.918, P =0.01). Our study indicated that the decreased expression of PDHA1 might be an independent prognostic factor in unfavorable outcomes.

The role of metastasis-associated in colon cancer 1 (MACC1) in endometrial carcinoma tumorigenesis and progression.

PubMed

Chen, Shuo; Zong, Zhi-Hong; Wu, Dan-Dan; Sun, Kai-Xuan; Liu, Bo-Liang; Zhao, Yang

2017-04-01

Metastasis-associated in colon cancer-1 (MACC1), has recently been identified as a key regulator in the progression of many cancers. However, its role in endometrial carcinoma (EC) remains unknown. MACC1 expression was determined in EC and normal endometrial tissues by immunohistochemistry. EC cell phenotypes and related molecules were examined after MACC1 downregulation by Small interfering RNA (siRNA) or microRNA (miRNA) transfection. We found that MACC1 was highly expressed in EC tissues than normal samples, and was significantly different in FIGO staging (I and II vs. III and IV), the depth of myometrial infiltration (<1/2 vs. ≥1/2), lymph nodes metastasis (negative vs. positive), besides, MACC1 overexpression was correlated with lower cumulative and relapse-free survival rate. MACC1 downregulation by siRNA transfection significantly induced G1 phrase arrest, suppressed EC cell proliferation, migration, and invasion. In addition, MACC1 downregulation also reduced expression of Cyclin D1 and Cyclin-dependent Kinase 2 (CDK2), N-cadherin (N-Ca), α-SMA, matrix metalloproteinase 2 (MMP2), and MMP9, but increased expression of E-cadherin (E-Ca). Bioinformatic predictions and dual-luciferase reporter assays indicate that MACC1 is a possible target of miR-23b. MiR-23b overexpression reduced MACC1 expression in vitro and induced G1 phrase arrest, suppressed cell proliferation, migration, and invasion. MiR-23b transfection also reduced Cyclin D1 and CDK2, N-Ca, α-SMA, MMP2, MMP9 expression, but increased E-Ca expression. Furthermore, the nude mouse xenograft assay showed that miR-23b overexpression suppressed tumour growth through downregulating MACC1 expression. Taken together, our results demonstrate for the first time that MACC1 may be a new and important diagnosis and therapeutic target of endometrial carcinoma. © 2017 Wiley Periodicals, Inc.

Comparison of Rai and Binet Classifications in Chronic Lymphocytic Leukemia.

PubMed

Zengin, N; Kars, A; Kansu, E; Özdemir, O; Barişta, İ; Güllü, İ; Güler, N; Özişik, Y; Dündar, S; Firat, D

1997-01-01

Staging systems are essential for understanding disease, in predicting the outcome, and therapeutic decision making in any tumor as well as chronic lymphocytic leukemia (CLL). In this study, we compared the clinical correlation of the Rai and Binet classification systems in 133 CLL patients. The distribution of 133 patients according to the Rai system was as follows, stage 0:17, I:13, II:45, III:30, IV:28, and in the Binet system stage A:35, B:40, C:58 patients. Median survival of patients according to the Rai staging system was >67.0, >91.0, 63.8, 20.9 and 9.8 months, and >91.0, 63.4, 16.0 months according to Binet, respectively. Although no difference was found between Rai stages 0, I, II (p > 0.05) in terms of median survival, the difference between these stages and stages III and IV was statistically significant (p < 0.05). In the Binet staging system statistically significant survival difference was found between all stages (p < 0.05). We concluded that although both systems are comparable in terms of staging and predicting the outcome of patients with CLL, the Rai staging system appears to have an advantage over the Binet system by defining a subset of patients with excellent prognosis (stage 0) which is included within stage A of the latter.

Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma.

PubMed

Cates, Justin M M

2017-03-01

The prognostic performance of the 2 most commonly used staging systems for skeletal sarcoma (the American Joint Committee on Cancer [AJCC] and Musculoskeletal Tumor Society [MSTS] systems) have never been compared analytically. Another staging system originally proposed by Spanier has not yet been validated. Given the recent release of the 8th edition of the AJCC Cancer Staging Manual, this study was designed to directly compare these anatomic staging systems in a series of 153 high-grade, intramedullary osteosarcomas. Kaplan-Meier curves were plotted and pairwise comparisons between each stage category were performed. Predictive accuracy of each staging system for determining 5-year disease-free survival was evaluated by comparing areas under receiver-operating characteristic curves generated from logistic regression analysis. Multiple concordance indices were calculated using bootstrapping methods (200 replications). ρk and R were estimated as measures of the variation in survival outcomes explained by the regression models. The AJCC, MSTS, and a modified version of the Spanier staging systems showed similar discriminatory abilities and no significant differences in the levels of contrast between different tumor stages across staging systems. Addition of T-category information from each staging system contributed significant prognostic information compared with a Cox proportional hazard regression model consisting only of the presence or absence of metastatic disease as a measure of disease extent. Concordance indices and predictive accuracy for 5-year disease-free survival were not significantly different among the different staging systems either. Similar findings were observed after accounting for other important prognostic variables. Additional studies are necessary to determine performance parameters of each staging system for other types of skeletal sarcoma. Prognostic performance of osteosarcoma staging systems would also be improved by incorporating nonanatomic prognostic variables into staging algorithms.

DEVELOPMENT OF COLD CLIMATE HEAT PUMP USING TWO-STAGE COMPRESSION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Bo; Rice, C Keith; Abdelaziz, Omar

2015-01-01

This paper uses a well-regarded, hardware based heat pump system model to investigate a two-stage economizing cycle for cold climate heat pump applications. The two-stage compression cycle has two variable-speed compressors. The high stage compressor was modelled using a compressor map, and the low stage compressor was experimentally studied using calorimeter testing. A single-stage heat pump system was modelled as the baseline. The system performance predictions are compared between the two-stage and single-stage systems. Special considerations for designing a cold climate heat pump are addressed at both the system and component levels.

Comparison of the King's and MiToS staging systems for ALS.

PubMed

Fang, Ton; Al Khleifat, Ahmad; Stahl, Daniel R; Lazo La Torre, Claudia; Murphy, Caroline; Young, Carolyn; Shaw, Pamela J; Leigh, P Nigel; Al-Chalabi, Ammar

2017-05-01

To investigate and compare two ALS staging systems, King's clinical staging and Milano-Torino (MiToS) functional staging, using data from the LiCALS phase III clinical trial (EudraCT 2008-006891-31). Disease stage was derived retrospectively for each system from the ALS Functional Rating Scale-Revised subscores using standard methods. The two staging methods were then compared for timing of stages using box plots, correspondence using chi-square tests, agreement using a linearly weighted kappa coefficient and concordance using Spearman's rank correlation. For both systems, progressively higher stages occurred at progressively later proportions of the disease course, but the distribution differed between the two methods. King's stage 3 corresponded to MiToS stage 1 most frequently, with earlier King's stages 1 and 2 largely corresponding to MiToS stage 0 or 1. The Spearman correlation was 0.54. There was fair agreement between the two systems with kappa coefficient of 0.21. The distribution of timings shows that the two systems are complementary, with King's staging showing greatest resolution in early to mid-disease corresponding to clinical or disease burden, and MiToS staging having higher resolution for late disease, corresponding to functional involvement. We therefore propose using both staging systems when describing ALS.

Assessment of the American Joint Commission on Cancer 8th Edition Staging System for Patients with Pancreatic Neuroendocrine Tumors: A Surveillance, Epidemiology, and End Results analysis.

PubMed

Li, Xiaogang; Gou, Shanmiao; Liu, Zhiqiang; Ye, Zeng; Wang, Chunyou

2018-03-01

Although several staging systems have been proposed for pancreatic neuroendocrine tumors (pNETs), the optimal staging system remains unclear. Here, we aimed to assess the application of the newly revised 8th edition American Joint Committee on Cancer (AJCC) staging system for exocrine pancreatic carcinoma (EPC) to pNETs, in comparison with that of other staging systems. We identified pNETs patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2014). Overall survival was analyzed using Kaplan-Meier curves with the log-rank test. The predictive accuracy of each staging system was assessed by the concordance index (c-index). Cox proportional hazards regression was conducted to calculate the impact of different stages. In total, 2424 patients with pNETs, including 2350 who underwent resection, were identified using SEER data. Patients with different stages were evenly stratified based on the 8th edition AJCC staging system for EPC. Kaplan-Meier curves were well separated in all patients and patients with resection using the 8th edition AJCC staging system for EPC. Moreover, the hazard ratio increased with worsening disease stage. The c-index of the 8th edition AJCC staging system for EPC was similar to that of the other systems. For pNETs patients, the 8th edition AJCC staging system for EPC exhibits good prognostic discrimination among different stages in both all patients and those with resection. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The IRIS-GUS Shuttle Borne Upper Stage System

NASA Technical Reports Server (NTRS)

Tooley, Craig; Houghton, Martin; Bussolino, Luigi; Connors, Paul; Broudeur, Steve (Technical Monitor)

2002-01-01

This paper describes the Italian Research Interim Stage - Gyroscopic Upper Stage (IRIS-GUS) upper stage system that will be used to launch NASA's Triana Observatory from the Space Shuttle. Triana is a pathfinder earth science mission being executed on rapid schedule and small budget, therefore the mission's upper stage solution had to be a system that could be fielded quickly at relatively low cost and risk. The building of the IRIS-GUS system wa necessary because NASA lost the capability to launch moderately sized upper stage missions fro the Space Shuttle when the PAM-D system was retired. The IRIS-GUS system restores this capability. The resulting system is a hybrid which mates the existing, flight proven IRIS (Italian Research Interim Stage) airborne support equipment to a new upper stage, the Gyroscopic Upper Stage (GUS) built by the GSFC for Triana. Although a new system, the GUS exploits flight proven hardware and design approaches in most subsystems, in some cases implementing proven design approaches with state-of-the-art electronics. This paper describes the IRIS-GUS upper stage system elements, performance capabilities, and payload interfaces.

Operation of staged membrane oxidation reactor systems

DOEpatents

Repasky, John Michael

2012-10-16

A method of operating a multi-stage ion transport membrane oxidation system. The method comprises providing a multi-stage ion transport membrane oxidation system with at least a first membrane oxidation stage and a second membrane oxidation stage, operating the ion transport membrane oxidation system at operating conditions including a characteristic temperature of the first membrane oxidation stage and a characteristic temperature of the second membrane oxidation stage; and controlling the production capacity and/or the product quality by changing the characteristic temperature of the first membrane oxidation stage and/or changing the characteristic temperature of the second membrane oxidation stage.

Comparison of the King’s and MiToS staging systems for ALS

PubMed Central

Fang, Ton; Al Khleifat, Ahmad; Stahl, Daniel R; Lazo La Torre, Claudia; Murphy, Caroline; Young, Carolyn; Shaw, Pamela J; Leigh, P Nigel; Al-Chalabi, Ammar

2017-01-01

Abstract Objective: To investigate and compare two ALS staging systems, King’s clinical staging and Milano-Torino (MiToS) functional staging, using data from the LiCALS phase III clinical trial (EudraCT 2008-006891-31). Methods: Disease stage was derived retrospectively for each system from the ALS Functional Rating Scale-Revised subscores using standard methods. The two staging methods were then compared for timing of stages using box plots, correspondence using chi-square tests, agreement using a linearly weighted kappa coefficient and concordance using Spearman’s rank correlation. Results: For both systems, progressively higher stages occurred at progressively later proportions of the disease course, but the distribution differed between the two methods. King’s stage 3 corresponded to MiToS stage 1 most frequently, with earlier King’s stages 1 and 2 largely corresponding to MiToS stage 0 or 1. The Spearman correlation was 0.54. There was fair agreement between the two systems with kappa coefficient of 0.21. Conclusion: The distribution of timings shows that the two systems are complementary, with King’s staging showing greatest resolution in early to mid-disease corresponding to clinical or disease burden, and MiToS staging having higher resolution for late disease, corresponding to functional involvement. We therefore propose using both staging systems when describing ALS. PMID:28054828

A stage is a stage is a stage: a direct comparison of two scoring systems.

PubMed

Dawson, Theo L

2003-09-01

L. Kohlberg (1969) argued that his moral stages captured a developmental sequence specific to the moral domain. To explore that contention, the author compared stage assignments obtained with the Standard Issue Scoring System (A. Colby & L. Kohlberg, 1987a, 1987b) and those obtained with a generalized content-independent stage-scoring system called the Hierarchical Complexity Scoring System (T. L. Dawson, 2002a), on 637 moral judgment interviews (participants' ages ranged from 5 to 86 years). The correlation between stage scores produced with the 2 systems was .88. Although standard issue scoring and hierarchical complexity scoring often awarded different scores up to Kohlberg's Moral Stage 2/3, from his Moral Stage 3 onward, scores awarded with the two systems predominantly agreed. The author explores the implications for developmental research.

A Gas-Spring-Loaded X-Y-Z Stage System for X-ray Microdiffraction Sample Manipulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shu Deming; Cai Zhonghou; Lai, Barry

2007-01-19

We have designed and constructed a gas-spring-loaded x-y-z stage system for x-ray microdiffraction sample manipulation at the Advanced Photon Source XOR 2-ID-D station. The stage system includes three DC-motor-driven linear stages and a gas-spring-based heavy preloading structure, which provides antigravity forces to ensure that the stage system keeps high-positioning performance under variable goniometer orientation. Microdiffraction experiments with this new stage system showed significant sample manipulation performance improvement.

A Gas-Spring-Loaded X-Y-Z Stage System for X-ray Microdiffraction Sample Manipulation

NASA Astrophysics Data System (ADS)

Shu, Deming; Cai, Zhonghou; Lai, Barry

2007-01-01

We have designed and constructed a gas-spring-loaded x-y-z stage system for x-ray microdiffraction sample manipulation at the Advanced Photon Source XOR 2-ID-D station. The stage system includes three DC-motor-driven linear stages and a gas-spring-based heavy preloading structure, which provides antigravity forces to ensure that the stage system keeps high-positioning performance under variable goniometer orientation. Microdiffraction experiments with this new stage system showed significant sample manipulation performance improvement.

Multi-stage fuel cell system method and apparatus

DOEpatents

George, Thomas J.; Smith, William C.

2000-01-01

A high efficiency, multi-stage fuel cell system method and apparatus is provided. The fuel cell system is comprised of multiple fuel cell stages, whereby the temperatures of the fuel and oxidant gas streams and the percentage of fuel consumed in each stage are controlled to optimize fuel cell system efficiency. The stages are connected in a serial, flow-through arrangement such that the oxidant gas and fuel gas flowing through an upstream stage is conducted directly into the next adjacent downstream stage. The fuel cell stages are further arranged such that unspent fuel and oxidant laden gases too hot to continue within an upstream stage because of material constraints are conducted into a subsequent downstream stage which comprises a similar cell configuration, however, which is constructed from materials having a higher heat tolerance and designed to meet higher thermal demands. In addition, fuel is underutilized in each stage, resulting in a higher overall fuel cell system efficiency.

The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report.

PubMed

Monclair, Tom; Brodeur, Garrett M; Ambros, Peter F; Brisse, Hervé J; Cecchetto, Giovanni; Holmes, Keith; Kaneko, Michio; London, Wendy B; Matthay, Katherine K; Nuchtern, Jed G; von Schweinitz, Dietrich; Simon, Thorsten; Cohn, Susan L; Pearson, Andrew D J

2009-01-10

The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system. To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known. In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% +/- 4% v 90% +/- 3%; P = .0010). Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.

Comparative performances of staging systems for early hepatocellular carcinoma.

PubMed

Nathan, Hari; Mentha, Gilles; Marques, Hugo P; Capussotti, Lorenzo; Majno, Pietro; Aldrighetti, Luca; Pulitano, Carlo; Rubbia-Brandt, Laura; Russolillo, Nadia; Philosophe, Benjamin; Barroso, Eduardo; Ferrero, Alessandro; Schulick, Richard D; Choti, Michael A; Pawlik, Timothy M

2009-08-01

Several staging systems for patients with hepatocellular carcinoma (HCC) have been proposed, but studies of their prognostic accuracy have yielded conflicting conclusions. Stratifying patients with early HCC is of particular interest because these patients may derive the greatest benefit from intervention, yet no studies have evaluated the comparative performances of staging systems in patients with early HCC. A retrospective cohort study was performed using data on 379 patients who underwent liver resection or liver transplantation for HCC at six major hepatobiliary centres in the USA and Europe. The staging systems evaluated were: the Okuda staging system, the International Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Japanese Integrated Staging (JIS) score and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, 6th edition. A recently proposed early HCC prognostic score was also evaluated. The discriminative abilities of the staging systems were evaluated using Cox proportional hazards models and the bootstrap-corrected concordance index (c). Overall survival of the cohort was 74% at 3 years and 52% at 5 years, with a median survival of 62 months. Most systems demonstrated poor discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c approximately 0.5). However, the AJCC/UICC system clearly stratified patients (P < 0.001, c = 0.59), albeit only into two groups. The early HCC prognostic score also clearly stratified patients (P < 0.001, c = 0.60) and identified three distinct prognostic groups. The early HCC prognostic score is superior to the AJCC/UICC staging system (6th edition) for predicting the survival of patients with early HCC after liver resection or liver transplantation. Other major HCC staging systems perform poorly in patients with early HCC.

Definition of compartment-based radical surgery in uterine cancer: modified radical hysterectomy in intermediate/high-risk endometrial cancer using peritoneal mesometrial resection (PMMR) by M Höckel translated to robotic surgery.

PubMed

Kimmig, Rainer; Aktas, Bahriye; Buderath, Paul; Wimberger, Pauline; Iannaccone, Antonella; Heubner, Martin

2013-08-16

The technique of compartment-based radical hysterectomy was originally described by M Höckel as total mesometrial resection (TMMR) for standard treatment of stage I and II cervical cancer. However, with regard to the ontogenetically-defined compartments of tumor development (Müllerian) and lymph drainage (Müllerian and mesonephric), compartments at risk may also be defined consistently in endometrial cancer. This is the first report in the literature on the compartment-based surgical approach to endometrial cancer. Peritoneal mesometrial resection (PMMR) with therapeutic lymphadenectomy (tLNE) as an ontogenetic, compartment-based oncologic surgery could be beneficial for patients in terms of surgical radicalness as well as complication rates; it can be standardized for compartment-confined tumors. Supported by M Höckel, PMMR was translated to robotic surgery (rPMMR) and described step-by-step in comparison to robotic TMMR (rTMMR). Patients (n = 42) were treated by rPMMR (n = 39) or extrafascial simple hysterectomy (n = 3) with/without bilateral pelvic and/or periaortic robotic therapeutic lymphadenectomy (rtLNE) for stage I to III endometrial cancer, according to International Federation of Gynecology and Obstetrics (FIGO) classification. Tumors were classified as intermediate/high-risk in 22 out of 40 patients (55%) and low-risk in 18 out of 40 patients (45%), and two patients showed other uterine malignancies. In 11 patients, no adjuvant external radiotherapy was performed, but chemotherapy was applied. No transition to open surgery was necessary. There were no intraoperative complications. The postoperative complication rate was 12% with venous thromboses, (n = 2), infected pelvic lymph cyst (n = 1), transient aphasia (n = 1) and transient dysfunction of micturition (n = 1). The mean difference in perioperative hemoglobin concentrations was 2.4 g/dL (± 1.2 g/dL) and one patient (2.4%) required transfusion. During follow-up (median 17 months), one patient experienced distant recurrence and one patient distant/regional recurrence of endometrial cancer (4.8%), but none developed isolated locoregional recurrence. There were two deaths from endometrial cancer during the observation period (4.8%). We conclude that rPMMR and rtLNE are feasible and safe with regard to perioperative morbidity, thus, it seems promising for the treatment of intermediate/high-risk endometrial cancer in terms of surgical radicalness and complication rates. This could be particularly beneficial for morbidly obese and seriously ill patients.

[Results of an individualized surgical therapy of vulvar carcinoma from 1973-1993].

PubMed

Köhler, U; Schöne, M; Pawlowitsch, T

1997-01-01

From 1973 through 1993, the University of Leipzig Women's Hospital treated 285 patients with primary vulvar malignancies. Of these, 269 cases (94.3%) were squamous cell carcinomas. The patients age averaged 69 years (25-95 years). 232 women (81.4%) were older than 60 years. Only 20 women (7%) were younger than 50 years. During the given time period, 266 patients (93.3%) underwent primary surgery. Standard operative treatment, performed in 105 cases (39.5%), was radical vulvectomy and bilateral superficial inguinal lymph node dissection. Rather than en bloc resection (Butterfly method), separate incisions were used during node dissection. Only 3 patients (2.9%) experienced a relapse within the remaining skin bridge. Irradiation with a focal doses of ca. 50 Gy followed postoperative-adjuvant in those cases involving the inguinal lymph nodes. In contrast, 161 patients received largely individualized surgical treatment. Local tumor extension and patient age-dependent operability influenced the choice of treatment. Partial vulvectomy was performed in 37 cases (13.9%). Simple vulvectomy without inguinal node dissection was performed in 115 cases (43.2%) and 9 patients underwent vulvectomy with vaginal-, urethral- and partial sphincter resection, accompanied by myocutaneous flap transposition (M. gluteus maximus lobe). The cumulative (corrected) 5-year survival rate for all patients with squamous cell carcinoma was 68.6%. No significant relationship between patient age (> 60 years vs. < or = 60 years) and prognosis could be seen. Factors of importance to the prognosis, however, were primary tumor size (FIGO stage I vs. II vs. III/IV), principal tumor site (significantly poorer survival rates characterize both clitoral and multifocal carcinomas), histological staging (G1 vs. G2/G3), inguinal lymph node involvement (pN+ vs. pN-) and degree of tumor resection in "healthy" (> or = 2 cm vs. < 2 cm). 5-year survival rates among those patients receiving individualized operative care did not differ significantly. Patient survival rates were 70.3% by partial vulvectomy, 78.2% by simple vulvectomy without inguinal node dissection and 67.6% by radical vulvectomy and bilateral inguinal node dissection with or without postoperative-adjuvant irradiation. These findings, therefore, justify the individualized operative treatment of patients with vulvar carcinoma according to each patient's initial prognostic situation. The relatively seldom vulvar carcinoma should only be treated by experienced surgeons in an appropriate hospital environment. Moreover, assessment of histological sections must be standardized, reproducible and above all, include the very accurate evaluation of all resection edges.

Survival benefits of pelvic lymphadenectomy versus pelvic and para-aortic lymphadenectomy in patients with endometrial cancer

PubMed Central

Guo, Weina; Cai, Jing; Li, Min; Wang, Hongbo; Shen, Yi

2018-01-01

Abstract Background: Despite that pelvic and para-aortic lymphadenectomy (PPaLND) is recommended as part of accurate surgical staging by International Federation of Gynecology and Obstetrics (FIGO) in endometrial cancer, the impact of para-aortic lymphadenectomy on survival remains controversial. The aim of this work is to evaluate the survival benefits or risks in endometrial cancer patients who underwent surgical staging with or without para-aortic lymphadenectomy using meta-analysis. Methods: Literature search was undertaken using PubMed, Embase, and Cochrane Library databases for relevant articles published between January 1, 1990, and January 1, 2017, without language restriction. The primary outcome was overall survival (OS); progression-free survival (PFS)/recurrence-free survival (RFS)/disease-free survival (DFS)/disease-related survival (DRS) was also analyzed. Subgroup analysis and sensitivity analysis were conducted to investigate the source of heterogeneity. Quality assessments were performed by Newcastle–Ottawa Quality Assessment Scale (NOS). Publication bias was evaluated by using Begg and Egger tests. The hazard ratio (HR) was pooled with random-effects or fixed-effects model as appropriate. Results: Eight studies with a total of 2793 patients were included. OS was significantly longer in PPaLND group than in pelvic lymphadenectomy (PLND) group for patients with endometrial cancer [HR 0.68; 95% confidence interval (CI) 0.55–0.84, P < .001, I2 = 12.2%]. Subgroup analysis by recurrence risk explored the same association in patients at intermediate- or high-risk (HR 0.52; 95% CI 0.39–0.69, P < .001, I2 = 41.4%), but not for low-risk patients (HR 0.48; 95% CI 0.21–1.08, P = .077, I2 = 0). PPaLND with systematic resection of all para-aortic nodes up to renal vein also improved PFS/RFS/DFS/DRS, compared with PLND (HR 0.52, 95% CI 0.37–0.72, P < .001, I2 = 0). No publication bias was observed among included studies. Conclusion: PPaLND is associated with favorable survival outcomes in endometrial cancer patients with intermediate- or high-risk of recurrence compared with PLND, particularly with regards to OS. PPaLND with systematic resection of all para-aortic nodes up to renal vein also improve PFS compared with PLND. Further large-scale randomized clinical trials are required to validate our findings. PMID:29505525

The International Neuroblastoma Risk Group (INRG) Staging System: An INRG Task Force Report

PubMed Central

Monclair, Tom; Brodeur, Garrett M.; Ambros, Peter F.; Brisse, Hervé J.; Cecchetto, Giovanni; Holmes, Keith; Kaneko, Michio; London, Wendy B.; Matthay, Katherine K.; Nuchtern, Jed G.; von Schweinitz, Dietrich; Simon, Thorsten; Cohn, Susan L.; Pearson, Andrew D.J.

2009-01-01

Purpose The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system. Methods To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known. Results In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% ± 4% v 90% ± 3%; P = .0010). Conclusion Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world. PMID:19047290

Development of a strategic plan by the Mozambican Association of Obstetricians and Gynaecologists: direct and indirect effects.

PubMed

Osman, Nafissa B; Almeida, Maria L; Ustá, Momade B; Bique, Cassimo; David, Ernestina

2014-10-01

The Mozambican Association of Obstetricians and Gynaecologists (AMOG) received support from the FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC) Initiative in Maternal and Newborn Health (MNH) to strengthen its organizational capacity and to assume leadership in MNH through the development of a strategic plan. The planning process involved identification of key stakeholders; analysis of strengths and weaknesses; stakeholder consultation; consultation with AMOG members; and ratification at the annual general meeting. The participatory process led to the development of vision and mission statements. Furthermore, core values and strategic goals were identified: (1) to contribute to the implementation of governmental plans for improving MNH; (2) to assume leadership in advancing the practice of obstetrics and gynecology through education and training; and (3) to continue to strengthen organizational capacity. Consequently, relationships among members were reinforced and the visibility and recognition of AMOG as a key stakeholder in MNH increased. Copyright © 2014. Published by Elsevier Ireland Ltd.

Changes in the use of manual vacuum aspiration for postabortion care within the public healthcare service network in Honduras.

PubMed

Chinchilla, Ana Ligia; Flores, Ivo Flores; Morales, Alma Fabiola; de Gil, Marina Padilla

2014-07-01

Honduras is one of the 17 priority countries included in the International Federation of Gynecology and Obstetrics (FIGO) Initiative for the Prevention of Unsafe Abortion and its Consequences. The priority category enables the country to request emergency funding to acquire services or commodities that could contribute toward achieving the objectives laid out in its plan of action. These objectives include improving postabortion care by increasing the use of manual vacuum aspiration (MVA) as an outpatient procedure with minimal human and material resources. Since the Ministry of Health lacked funding, use of the emergency fund was approved for the purchase and distribution of MVA kits nationwide to ensure continuity and the hope of increasing MVA use. Eleven hospitals participating in this initiative provided data for analysis of the outcome. These data show no increase in MVA use; however, as discussed in the article, further investigation provided valuable information on the reasons behind these results. Copyright © 2014. Published by Elsevier Ireland Ltd.

Contribution of obstetrics and gynecology societies in West and Central African countries to the prevention of unsafe abortion.

PubMed

Leke, Robert J I

2014-07-01

Unsafe abortion is a major public health issue in low-resource countries. In the countries of West and Central Africa, abortion-related maternal mortality rates are extremely high, the prevalence of modern contraceptive use is very low, and the unmet need for family planning is also high. The International Federation of Gynecology and Obstetrics (FIGO) Initiative for the Prevention of Unsafe Abortion and its Consequences has contributed substantially toward increasing awareness of the problem of abortion, bringing abortion-related issues to the attention of the professional societies, individual gynecologists and obstetricians, Ministries of Health, healthcare providers, and to the community in general. The promotion of quality postabortion care including the use of manual vacuum aspiration, misoprostol, and postabortion contraception has greatly improved access to services; however, there is still a long way to go. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Altered peroxisome-proliferator activated receptors expression in human endometrial cancer.

PubMed

Knapp, Paweł; Chabowski, Adrian; Błachnio-Zabielska, Agnieszka; Jarząbek, Katarzyna; Wołczyński, Sławomir

2012-01-01

Peroxisome proliferator-activated receptors (PPARs) belong to a family of nuclear hormone receptors acting as transcriptional factors, recently involved also in carcinogenesis. Present study was undertaken to evaluate the presence and subcellular localization of different PPAR isoforms (α, β, γ) in healthy endometrial tissue (n = 10) and endometrial carcinoma (FIGO I, endometrioides type, G1, n = 35). We sought to analyze PPARs mRNA content as well as protein immunohistochemical expression that was further quantified by Western Blot technique. For both PPARα and PPARβ, protein expression was significantly higher in endometrial cancers compared to normal endometrial mucosa. In opposite, PPARγ protein expression was lower in endometrial cancer cells. In each case, immunohistochemical reaction was confined to the perinuclear and/or nuclear region. At the transcriptional level, the content of mRNA of all PPAR subunits did not follow the protein pattern of changes. These results provide evidence for altered PPAR's protein expression and disregulation of posttranslational processes in endometrial cancers.

Adenomyosis and Abnormal Uterine Bleeding (AUB-A)-Pathogenesis, diagnosis, and management.

PubMed

Abbott, Jason A

2017-04-01

The complex pathogenesis and variable presentation of adenomyosis make it one of the most difficult of the FIGO PALM-COIEN abnormal uterine bleeding group to diagnose and treat. Basic clinical parameters such as prevalence are difficult to accurately assess because histological confirmation is usually employed; however, because of the access to and accuracy and utilization of transvaginal ultrasound and other advanced imaging techniques such as MRI, noninvasive diagnosis is recognized to be highly accurate. The clinical symptoms of pain, abnormal uterine bleeding, and subfertility are the primary presentations of adenomyosis with increasing data supporting a substantial role of this disease in reducing fecundity and interfering with assisted reproductive interventions. Treatments have been aimed at managing symptoms and improving fertility options. Management by hysterectomy is not always desired by women, and with many women having children in their fourth and even fifth decades, it is often not reasonable to consider this radical option. Copyright © 2016. Published by Elsevier Ltd.

Sexual and reproductive health and HIV services: integrating HIV/AIDS and cervical cancer prevention and control.

PubMed

Belhadj, Hedia; Rasanathan, Jennifer J K; Denny, Lynette; Broutet, Nathalie

2013-05-01

People living with HIV are at an increased risk of acquiring HPV and of developing evolutive cervical cancers (women) and penile and anal cancers (men). Low-cost screening-visual inspection with acetic acid, HPV DNA diagnostics and primary care level treatment, cryotherapy for cervical intraepithelial neoplasia (CIN 2), and primary prevention through HPV vaccination of girls aged 9-13 years-makes the goal of eliminating cervical cancer possible in the long term. Integration of cervical cancer screening and treatment into a sexual and reproductive health service package raises programmatic questions and calls for a continuum of care. The latter is only possible when adequate cytopathology skills and treatment for advanced cancer conditions are available. The present paper highlights the role of member societies of the International Federation of Gynecology and Obstetrics (FIGO) in developing the base for an integrated package that responds to women's sexual and reproductive health needs. Copyright © 2013 International Federation of Gynecology and Obstetrics. All rights reserved.

Impact of Chemotherapy on Retroperitoneal Lymph Nodes in Ovarian Cancer.

PubMed

Keyver-Paik, Mignon-Denise; Arden, Janne Myriam; Lüders, Christine; Thiesler, Thore; Abramian, Alina; Hoeller, Tobias; Hecking, Thomas; Ayub, Tiyasha Hosne; Doeser, Anna; Kaiser, Christina; Kuhn, Walther

2016-04-01

Complete cytoreduction is the most important prognostic factor in ovarian cancer. However, there exist conflicting data on whether the removal of microscopic tumor metastasis in macroscopically unsuspicious retroperitoneal lymph nodes is beneficial. Ovarian cancer tissues and tissues from lymph node metastasis of 30 patients with FIGO IIIC or IV disease undergoing neoadjuvant chemotherapy (NACT) were obtained and assessed using a validated regression score. Histopathological markers, size of largest tumor focus, and overall score were evaluated in lymph node and ovarian tissue. Regression and known prognostic factors were analyzed for influence on survival. No difference in the overall score between lymph nodes and ovarian tissue was shown, however, single parameters such as fibrosis and pattern of tumor infiltration, were significantly different. The pattern of tumor regression in lymph nodes and ovarian tissue are of prognostic value. Lymph node dissection even of unsuspicious nodes should, therefore, be performed. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Coupling effect and control strategies of the maglev dual-stage inertially stabilization system based on frequency-domain analysis.

PubMed

Lin, Zhuchong; Liu, Kun; Zhang, Li; Zeng, Delin

2016-09-01

Maglev dual-stage inertially stabilization (MDIS) system is a newly proposed system which combines a conventional two-axis gimbal assembly and a 5-DOF (degree of freedom) magnetic bearing with vernier tilting capacity to perform dual-stage stabilization for the LOS of the suspended optical instrument. Compared with traditional dual-stage system, maglev dual-stage system exhibits different characteristics due to the negative position stiffness of the magnetic forces, which introduces additional coupling in the dual stage control system. In this paper, the coupling effect on the system performance is addressed based on frequency-domain analysis, including disturbance rejection, fine stage saturation and coarse stage structural resonance suppression. The difference between various control strategies is also discussed, including pile-up(PU), stabilize-follow (SF) and stabilize-compensate (SC). A number of principles for the design of a maglev dual stage system are proposed. A general process is also suggested, which leads to a cost-effective design striking a balance between high performance and complexity. At last, a simulation example is presented to illustrate the arguments in the paper. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Design options for advanced manned launch systems

NASA Astrophysics Data System (ADS)

Freeman, Delma C.; Talay, Theodore A.; Stanley, Douglas O.; Lepsch, Roger A.; Wilhite, Alan W.

1995-03-01

Various concepts for advanced manned launch systems are examined for delivery missions to space station and polar orbit. Included are single-and two-stage winged systems with rocket and/or air-breathing propulsion systems. For near-term technologies, two-stage reusable rocket systems are favored over single-stage rocket or two-stage air-breathing/rocket systems. Advanced technologies enable viable single-stage-to-orbit (SSTO) concepts. Although two-stage rocket systems continue to be lighter in dry weight than SSTO vehicles, advantages in simpler operations may make SSTO vehicles more cost-effective over the life cycle. Generally, rocket systems maintain a dry-weight advantage over air-breathing systems at the advanced technology levels, but to a lesser degree than when near-term technologies are used. More detailed understanding of vehicle systems and associated ground and flight operations requirements and procedures is essential in determining quantitative discrimination between these latter concepts.

The AJCC 8th Edition Staging System for Soft Tissue Sarcoma of the Extremities or Trunk: A Cohort Study of the SEER Database.

PubMed

Cates, Justin M M

2018-02-01

Background: The AJCC recently published the 8th edition of its cancer staging system. Significant changes were made to the staging algorithm for soft tissue sarcoma (STS) of the extremities or trunk, including the addition of 2 additional T (size) classifications in lieu of tumor depth and grouping lymph node metastasis (LNM) with distant metastasis as stage IV disease. Whether these changes improve staging system performance is questionable. Patients and Methods: This retrospective cohort analysis of 21,396 adult patients with STS of the extremity or trunk in the SEER database compares the AJCC 8th edition staging system with the 7th edition and a newly proposed staging algorithm using a variety of statistical techniques. The effect of tumor size on disease-specific survival was assessed by flexible, nonlinear Cox proportional hazard regression using restricted cubic splines and fractional polynomials. Results: The slope of covariate-adjusted log hazards for sarcoma-specific survival decreases for tumors >8 cm in greatest dimension, limiting prognostic information contributed by the new T4 classification in the AJCC 8th edition. Anatomic depth independently provides significant prognostic information. LNM is not equivalent to distant, non-nodal metastasis. Based on these findings, an alternative staging system is proposed and demonstrated to outperform both AJCC staging schemes. The analyses presented also disclose no evidence of improved clinical performance of the 8th edition compared with the previous edition. Conclusions: The AJCC 8th edition staging system for STS is no better than the previous 7th edition. Instead, a proposed staging system based on histologic grade, tumor size, and anatomic depth shows significantly higher predictive accuracy, with higher model concordance than either AJCC staging system. Changes to existing staging systems should improve the performance of prognostic models. Until such improvements are documented, AJCC committees should refrain from modifying established staging schemes. Copyright © 2018 by the National Comprehensive Cancer Network.

A modified TNM staging system for non-metastatic colorectal cancer based on nomogram analysis of SEER database.

PubMed

Kong, Xiangxing; Li, Jun; Cai, Yibo; Tian, Yu; Chi, Shengqiang; Tong, Danyang; Hu, Yeting; Yang, Qi; Li, Jingsong; Poston, Graeme; Yuan, Ying; Ding, Kefeng

2018-01-08

To revise the American Joint Committee on Cancer TNM staging system for colorectal cancer (CRC) based on a nomogram analysis of Surveillance, Epidemiology, and End Results (SEER) database, and to prove the rationality of enhancing T stage's weighting in our previously proposed T-plus staging system. Total 115,377 non-metastatic CRC patients from SEER were randomly grouped as training and testing set by ratio 1:1. The Nomo-staging system was established via three nomograms based on 1-year, 2-year and 3-year disease specific survival (DSS) Logistic regression analysis of the training set. The predictive value of Nomo-staging system for the testing set was evaluated by concordance index (c-index), likelihood ratio (L.R.) and Akaike information criteria (AIC) for 1-year, 2-year, 3-year overall survival (OS) and DSS. Kaplan-Meier survival curve was used to valuate discrimination and gradient monotonicity. And an external validation was performed on database from the Second Affiliated Hospital of Zhejiang University (SAHZU). Patients with T1-2 N1 and T1N2a were classified into stage II while T4 N0 patients were classified into stage III in Nomo-staging system. Kaplan-Meier survival curves of OS and DSS in testing set showed Nomo-staging system performed better in discrimination and gradient monotonicity, and the external validation in SAHZU database also showed distinctly better discrimination. The Nomo-staging system showed higher value in L.R. and c-index, and lower value in AIC when predicting OS and DSS in testing set. The Nomo-staging system showed better performance in prognosis prediction and the weight of lymph nodes status in prognosis prediction should be cautiously reconsidered.

Re-Evaluation of 6th Edition of AJCC Staging System for Nasopharyngeal Carcinoma and Proposed Improvement Based on Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao Yanping; Xie Fangyun; Liu Lizhi

2009-04-01

Purpose: To use magnetic resonance imaging to re-evaluate and improve the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. Methods and Materials: We performed a retrospective review of the data from 924 biopsy-proven nonmetastatic nasopharyngeal carcinoma cases. All patients had undergone magnetic resonance imaging examinations and received radiotherapy as their primary treatment. Results: The T classification, N classification, and stage group were independent predictors. No significant differences in the local failure hazards between adjacent T categories were observed between Stage T2b and T1, Stage T2b and T2a, and Stage T2b andmore » T3. Although the disease failure hazards for Stage T1 were similar to those for Stage T2a, those for Stage T2b were similar to those for Stage T3. Survival curves of the different T/N subsets showed a better segregation when Stage T2a was downstaged to T1, T2b and T3 were incorporated into T2, and the nodal greatest dimension was rejected. The disease failure hazard for T3N0-N1 subsets were similar to those of the T1-T2N1 subsets belonging to Stage II; the same result was found for the T4N0-N2 subsets in the sixth American Joint Committee on Cancer staging system. However, the staging system we propose shows more consistent hazards within the same stage group and better survival discrimination among T categories, N categories, and overall stages. Conclusion: Using the 6th American Joint Committee on Cancer staging system produces an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorizing the T, N, and group stage criteria.« less

[Helicobacter pylori gastritis: assessment of OLGA and OLGIM staging systems].

PubMed

Ben Slama, Sana; Ben Ghachem, Dorra; Dhaoui, Amen; Jomni, Mohamed Taieb; Dougui, Mohamed Hédi; Bellil, Khadija

2016-01-01

Helicobacter pylori (H pylori) gastritis presents a risk of cancer related to atrophy and intestinal metaplasia. Two recent classifications OLGA (Operative Link on Gastritis Assessment) and OLGIM (Operative Link on Gastritic Intestinal Metaplasia assessment) have been proposed to identify high-risk forms (stages III and IV). The aim of this study is to evaluate the OLGA and OLGIM staging systems in H pylori gastritis. A descriptive study of 100 cases of chronic H pylori gastritis was performed. The revaluation of Sydney System parameters of atrophy and intestinal metaplasia, of gastric antrum and corpus, allowed identifying respectively the stages of OLGA and OLGIM systems. The progressive risk of our H pylori gastritis was 6% according to OLGA staging and 7% according to OLGIM staging. Significant correlation was revealed between age and OLGA staging. High-risk gastritis according to OLGIM staging was significantly associated with moderate to severe atrophy. High-risk forms according to OLGA staging were associated in 80% of the cases to intestinal metaplasia. OLGA and OLGIM systems showed a highly significant positive correlation between them with a mismatch at 5% for H pylori gastritis. The OLGA and OLGIM staging systems in addition to Sydney System, allow selection of high risk forms of chronic gastritis requiring accurate observation.

Assessment of the Hong Kong Liver Cancer Staging System in Europe.

PubMed

Kolly, Philippe; Reeves, Helen; Sangro, Bruno; Knöpfli, Marina; Candinas, Daniel; Dufour, Jean-François

2016-06-01

European and American guidelines have endorsed the Barcelona Clinic Liver Cancer (BCLC) staging system. The aim of this study was to assess the performance of the recently developed Hong Kong Liver Cancer (HKLC) classification as a staging system for hepatocellular carcinoma (HCC) in Europe. We used a pooled set of 1693 HCC patients combining three prospective European cohorts. Discrimination ability between the nine substages and five stages of the HKLC classification system was assessed. To evaluate the predictive power of the HKLC and BCLC staging systems on overall survival, Nagelkerke pseudo R2, Bayesian Information Criterion and Harrell's concordance index were calculated. The number of patients who would benefit from a curative therapy was assessed for both staging systems. The HKLC classification in nine substages shows suboptimal discrimination between the staging groups. The classification in five stages shows better discrimination between groups. However, the BCLC classification performs better than the HKLC classification in the ability to predict overall survival (OS). The HKLC treatment algorithm tags significantly more patients to curative therapy than the BCLC. The BCLC staging system performs better for European patients than the HKLC staging system in predicting OS. Twice more patients are eligible for a curative therapy with the HKLC algorithm; whether this translates in survival benefit remains to be investigated. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mineralogy, paragenesis, and mineral zoning of the Bulldog Mountain vein system, Creede District, Colorado

USGS Publications Warehouse

Plumlee, Geoffrey S.; Heald Whitehouse-Veaux, Pamela

1994-01-01

The Bulldog Mountain vein system, Creede district, Colorado, is one of four major epithermal vein systems from which the bulk of the district's historical Ag-Pb-Zn-Cu production has come. Ores deposited along the vein system were discovered in 1965 and were mined from 1969 to 1985.Six temporally gradational mineralization stages have been identified along the Bulldog Mountain vein system, each with a characteristic suite of minerals deposited or leached and a characteristic distribution within the vein system; some of these stages are also strongly zoned within the vein system. Stage A was dominated by deposition of rhodochrosite along the lower levels of the Bulldog Mountain ore zone. Stage B in the northern parts of the ore zone is characterized by abundant fine-grained sphalerite and galena, with lesser tetrahedrite and minor chlorite and hematite. With increasing elevation to the south, stage B ores become progressively more barite and silver rich, with alternating barite and fine-grained sphalerite + galena generations; native silver + or - acanthite assemblages are also locally abundant within southern stage B barite sulfide ores, whereas chalcopyrite and other Cu and Ag sulfides and sulfosalts are present erratically in minor amounts. Stage C in the upper and northern portions of the ore zone is characterized by abundant quartz and fluorite, minor adularia, hematite, Mn siderite, sphalerite, and galena, and major leaching of earlier barite; to the south, some barite and sulfides may have been deposited. Stage D sphalerite and galena were deposited in the upper and northern portions of the ore zone; a barite- and silver-rich facies of this stage may also be present in the southern portions of the vein system. Late in stage D, mineralogically complex assemblages containing chalcopyrite, tetrahedrite, polybasite, bornite, pyrargyrite, and a variety of other sulfides and sulfosalts were deposited in modest amounts throughout the vein system. This complex assemblage marked the transition to stage E. During stage E, the final sulfide stage, abundant botryoidal pyrite and marcasite with lesser stibnite, sphalerite, and sulfosalts were deposited primarily along the top of the Bulldog Mountain ore zone. Stage F, the final mineralization stage along the vein system, is marked by wire silver and concurrent leaching of earlier sulfides and sulfosalts; this stage may reflect the transition to a supergene environment.The sequence of mineralization stages identified in this study along the Bulldog Mountain system can be correlated with corresponding stages identified by other researchers along the OH and P veins, and the southern Amethyst vein system. Mineral zoning patterns identified along the Bulldog Mountain vein system also parallel larger scale zoning patterns across the central and southern Creede district.The complex variations in mineral assemblages documented in time and space along the Bulldog Mountain vein system were produced by the combined effects of many processes. Large-scale changes in vein mineralogy over time produced discrete mineralization stages. Short-term mineralogical fluctuations produced complex interbanding of mineralogically distinct generations. Fluid chemistry evolution within the vein system produced large-scale lateral zoning patterns within certain stages. Hypogene leaching substantially modified the distributions of some minerals. Finally, structural activity, mineral deposition, and mineral leaching modified fluid flow pathways repeatedly during mineralization, and so added to the complex mineral distribution patterns within the vein system.

Juvenile nasopharyngeal angiofibroma staging: An overview.

PubMed

Alshaikh, Nada Ali; Eleftheriadou, Anna

2015-06-01

Staging of tumors is very important in treatment and surgical decision making, as well as in predicting disease recurrence and prognosis. This review focuses on the different available classifications of juvenile nasopharyngeal angiofibroma (JNA) and their impact on the evaluation, management, and prognosis of JNA. The literature was reviewed, and publications on JNA staging were examined. Our MEDLINE search of the entire English-language literature found no review article on the current available staging systems for JNA. In this article, we review the common JNA classification systems that have been published, and we discuss some of their advantages and disadvantages. The most commonly used staging systems for JNA are the Radkowski and the Andrews-Fisch staging systems. However, some newer staging systems that are based on advances in technology and surgical approaches-the Onerci, INCan, and UPMC systems-have shown promising utility, and they will probably gain popularity in the future.

Comparison of five systems for staging lymph node metastasis in gastric cancer.

PubMed

Yu, W; Choi, G S; Whang, I; Suh, I S

1997-09-01

There are several systems for staging lymph node metastasis in gastric cancer. Their relative merits are not clear. In this retrospective analysis, the nodal status was classified according to the Union Internacional Contra la Cancrum (UICC) and Japanese staging systems, the number and frequency of lymph node metastasis, and the level of involved nodes. Each staging system was scored as good (+1), fair (0) or poor (-1) with respect to prognostic value, theoretical value, convenience, reproducibility and surgical applicability. There were no differences between the five staging systems in predicting survival. The Japanese staging system was most arbitrary owing to the complexity of the system, although it had an advantage in surgical application. The same disadvantage was found in the UICC system and the level system. Determination of the number and frequency of involved nodes was convenient and reproducible, but the number of lymph nodes dissected must be considered when the number of positive nodes is used for staging. The classification of metastasis to the regional lymph nodes as N0 (no nodal metastasis), N1 (metastasis in 1-25 per cent of dissected nodes) and N2 (metastasis in more than 25 per cent of dissected nodes) would be a simple, convenient, reproducible staging system with an ability to predict surgical results.

Understanding cancer staging

MedlinePlus

... detailed information about the cancer stage. TNM Staging System The most common system for staging cancer in ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Intestinal diffuse large B-cell lymphoma: an evaluation of different staging systems.

PubMed

Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Park, Chan-Sik; Huh, Jooryung

2014-01-01

The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.

Strutjet-powered reusable launch vehicles

NASA Technical Reports Server (NTRS)

Siebenhaar, A.; Bulman, M. J.; Sasso, S. E.; Schnackel, J. A.

1994-01-01

Martin Marietta and Aerojet are co-investigating the feasibility and viability of reusable launch vehicle designs. We are assessing two vehicle concepts, each delivering 8000 lb to a geosynchronous transfer orbit (GTO). Both accomplish this task as a two-state system. The major difference between the two concepts is staging. The first concept, the two-stage-to-orbit (TSTO) system, stages at about 16 kft/sec, allowing immediate return of the first stage to the launch site using its airbreathing propulsion system for a powered cruise flight. The second concept, the single-stage-to-orit (SSTO) system, accomplishes stage separation in a stable low earth orbit (LEO).

Advanced Hepatocellular Carcinoma: Which Staging Systems Best Predict Prognosis?

PubMed Central

Huitzil-Melendez, Fidel-David; Capanu, Marinela; O'Reilly, Eileen M.; Duffy, Austin; Gansukh, Bolorsukh; Saltz, Leonard L.; Abou-Alfa, Ghassan K.

2010-01-01

Purpose The purpose of cancer staging systems is to accurately predict patient prognosis. The outcome of advanced hepatocellular carcinoma (HCC) depends on both the cancer stage and the extent of liver dysfunction. Many staging systems that include both aspects have been developed. It remains unknown, however, which of these systems is optimal for predicting patient survival. Patients and Methods Patients with advanced HCC treated over a 5-year period at Memorial Sloan-Kettering Cancer Center were identified from an electronic medical record database. Patients with sufficient data for utilization in all staging systems were included. TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH) systems were ranked on the basis of their accuracy at predicting survival by using concordance index (c-index). Other independent prognostic variables were also identified. Results Overall, 187 eligible patients were identified and were staged by using the seven staging systems. CLIP, CUPI, and GETCH were the three top-ranking staging systems. BCLC and TNM sixth edition lacked any meaningful prognostic discrimination. Performance status, AST, abdominal pain, and esophageal varices improved the discriminatory ability of CLIP. Conclusion In our selected patient population, CLIP, CUPI, and GETCH were the most informative staging systems in predicting survival in patients with advanced HCC. Prospective validation is required to determine if they can be accurately used to stratify patients in clinical trials and to direct the appropriate need for systemic therapy versus best supportive care. BCLC and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data. PMID:20458042

Prognosis of canine patients with nasal tumors according to modified clinical stages based on computed tomography: a retrospective study.

PubMed

Kondo, Yumi; Matsunaga, Satoru; Mochizuki, Manabu; Kadosawa, Tsuyoshi; Nakagawa, Takayuki; Nishimura, Ryohei; Sasaki, Nobuo

2008-03-01

To evaluate the efficacy of clinical staging based on computed tomography (CT) imaging over the World Health Organization (WHO) staging system based on radiography for nasal tumors in dogs, a retrospective study was conducted. This study used 112 dogs that had nasal tumors; they had undergone radiography and CT and had been histologically confirmed as having nasal tumors. Among 112 dogs, 85 (75.9%) were diagnosed as adenocarcinoma. Then they were analyzed for survival time according to each staging system. More than 70% of the patients with adenocarcinoma were classified as having WHO stage III. The patients classified under WHO stage II tended to survive longer than those classified under WHO stage III. Dogs classified under WHO stage III were further grouped into CT stages III and IV, and CT stage III patients had a significantly longer survival time than CT stage IV patients. In addition, patients treated with a combination of surgery and radiation had a significantly longer survival time than the patients who did not receive any treatment in CT stage III. On the other hand, different treatment modalities did not show a significant difference in the survival time of CT stage IV dogs. The results suggest that WHO stage III dogs may have various levels of tumor progression, indicating that the CT staging system may be more accurate than the WHO staging system.

Evaluation of two-stage system for neutron measurement aiming at increase in count rate at Japan Atomic Energy Agency-Fusion Neutronics Source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shinohara, K., E-mail: shinohara.koji@jaea.go.jp; Ochiai, K.; Sukegawa, A.

In order to increase the count rate capability of a neutron detection system as a whole, we propose a multi-stage neutron detection system. Experiments to test the effectiveness of this concept were carried out on Fusion Neutronics Source. Comparing four configurations of alignment, it was found that the influence of an anterior stage on a posterior stage was negligible for the pulse height distribution. The two-stage system using 25 mm thickness scintillator was about 1.65 times the count rate capability of a single detector system for d-D neutrons and was about 1.8 times the count rate capability for d-T neutrons.more » The results suggested that the concept of a multi-stage detection system will work in practice.« less

Validation of the Mayo Clinic Staging System in Determining Prognoses of Patients With Perihilar Cholangiocarcinoma.

PubMed

Coelen, Robert J S; Gaspersz, Marcia P; Labeur, Tim A; van Vugt, Jeroen L A; van Dieren, Susan; Willemssen, François E J A; Nio, Chung Y; IJzermans, Jan N M; Klümpen, Heinz-Josef; Groot Koerkamp, Bas; van Gulik, Thomas M

2017-12-01

Most systems for staging perihilar cholangiocarcinoma (PHC) have been developed for the minority of patients with resectable disease. The recently developed Mayo Clinic system for staging PHC requires only clinical and radiologic variables, but has not yet been validated. We performed a retrospective study to validate the Mayo Clinic staging system. We identified consecutive patients with suspected PHC who were evaluated and treated at 2 tertiary centers in The Netherlands, from January 2002 through December 2014. Baseline characteristics (performance status, carbohydrate antigen 19-9 level) used in the staging system were collected from medical records and imaging parameters (tumor size, suspected vascular involvement, and metastatic disease) were reassessed by 2 experienced abdominal radiologists. Overall survival was analyzed using the Kaplan-Meier method and comparison of staging groups was performed using the log-rank test and Cox proportional hazard regression analysis. Discriminative performance was quantified by the concordance index and compared with the radiologic TNM staging of the American Joint Committee on Cancer (7th ed). PHCs from 600 patients were staged according to the Mayo Clinic model (23 stage I, 80 stage II, 357 stage III, and 140 stage IV). The median overall survival time was 11.6 months. The median overall survival times for patients with stages I, II, III, and IV were 33.2 months, 19.7 months, 12.1 months, and 6.0 months, respectively; with hazard ratios of 1.0 (reference), 2.02 (95% confidence interval [CI], 1.14-3.58), 2.71 (95% CI, 1.59-4.64), and 4.00 (95% CI, 2.30-6.95), respectively (P < .001). The concordance index score was 0.59 for the entire cohort (95% CI, 0.56-0.61). The Mayo Clinic model performed slightly better than the radiologic American Joint Committee on Cancer TNM system. In a retrospective study of 600 patients with PHC, we validated the Mayo Clinic system for staging PHC. This 4-tier staging system may aid clinicians in making treatment decisions, such as referral for surgery, and predicting survival times. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Morphogenesis of the human excretory lacrimal system

PubMed Central

de la Cuadra-Blanco, C; Peces-Peña, M D; Jáñez-Escalada, L; Mérida-Velasco, J R

2006-01-01

The aim of this study was to determine the principal developmental stages in the formation of the excretory lacrimal system in humans and to establish its morphogenetic period. The study was performed using light microscopy on serial sections of 51 human specimens: 33 embryos and 18 fetuses ranging from 8 to 137 mm crown–rump length (CR; 5–16 weeks of development). Three stages were identified in the morphogenesis of the excretory lacrimal system: (1) the formative stage of the lacrimal lamina (Carnegie stages 16–18); (2) the formative stage of the lacrimal cord (Carnegie stages 19–23); and (3) the maturative stage of the excretory lacrimal system, from the 9th week of development onward. A three-dimensional reconstruction of the excretory lacrimal system was performed from serial sections of an embryo at the end of the embryonic period (27 mm CR). PMID:16879594

Seventh edition (2010) of the AJCC/UICC staging system for gastric adenocarcinoma: is there room for improvement?

PubMed

Patel, Manali I; Rhoads, Kim F; Ma, Yifei; Ford, James M; Visser, Brendan C; Kunz, Pamela L; Fisher, George A; Chang, Daniel T; Koong, Albert; Norton, Jeffrey A; Poultsides, George A

2013-05-01

The gastric cancer AJCC/UICC staging system recently underwent significant revisions, but studies on Asian patients have reported a lack of adequate discrimination between various consecutive stages. We sought to validate the new system on a U.S. population database. California Cancer Registry data linked to the Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (esophagogastric junction and gastric cardia tumors excluded) who underwent curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC stage was recalculated based on the latest seventh edition. Overall survival probabilities were calculated using the Kaplan-Meier method. Of 1905 patients analyzed, 54 % were males with a median age of 70 years. Median number of pathologically examined lymph nodes was 12 (range, 1-90); 40 % of patients received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The seventh edition AJCC/UICC system did not distinguish outcome adequately between stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system with improved discriminatory ability In this first study validating the new seventh edition AJCC/UICC staging system for gastric cancer on a U.S. population with a relatively limited number of lymph nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC/UICC staging system that better discriminates between outcomes.

Design of the ultraprecision stage for lithography using VCM

NASA Astrophysics Data System (ADS)

Kim, Jung-Han; Kim, Mun-Su; Oh, Min-Taek

2007-12-01

This paper presents a new design of precision stage for the reticle in lithography process and a low hunting control method for the stage. The stage has three axes for X,Y, θ Z, those actuated by three voice coil motors individually. The proposed precision stage system has three gap sensors and voice coil motors, and supported by four air bearings, so it do not have any mechanical contact and nonlinear effect such as hysterisis which usually degrade performance in nano level movement. The reticle stage has cross coupled dynamics between X,Y,θ Z, axes, so the forward and inverse kinematics were solved to get an accurate reference position. When the stage is in regulating control mode, there always exist small fluctuations (stage hunting) in the stage movement. Because the low stage hunting characteristic is very important in recent lithography and nano-level applications, the proposed stage has a special regulating controller composed of digital filter, adjustor and switching algorithm. Another importance factor that generates hunting noise is the system noise inside the lithography machine such as EMI from another motor and solenoids. For reducing such system noises, the proposed controller has a two-port transmission system that transfers torque command signal from the DSP board to the amplifier. The low hunting control algorithm and two-port transmission system reduced hunting noise as 35nm(rms) when a conventional PID generates 77nm(rms) in the same mechanical system. The experimental results showed that the reticle system has 100nm linear accuracy and 1μ rad rotation accuracy at the control frequency of 8 kHz.

[Interpretation of update on The AJCC Esophageal Cancer Staging System, Eighth Edition].

PubMed

Yuan, Y; Chen, L Q

2017-02-01

The recently published AJCC Esophageal Cancer Staging System, 8(th) Edition will be implemented on Januray 1, 2018, which was developed by Worldwide Esophageal Cancer Collaboration based on 22 654 esophageal cancer patients from 33 worldwide centers. The definition of T, N, M, G stage and regional lymph nodes were optimized in the 8(th) edition. And the new "2 cm" principle has simplified the definition for the cancer of esophagogastric junction. In addition to pathologic staging, the 8(th) edition also provided clinical staging and pathologic staging after neoadjuvant therapy, making the new esophageal cancer staging system more practicable and reasonable.

Development and testing of a de novo clinical staging system for podoconiosis (endemic non-filarial elephantiasis).

PubMed

Tekola, Fasil; Ayele, Zewdu; Mariam, Dereje Haile; Fuller, Claire; Davey, Gail

2008-10-01

To develop and test a robust clinical staging system for podoconiosis, a geochemical disease in individuals exposed to red clay soil. We adapted the Dreyer system for staging filarial lymphoedema and tested it in four re-iterative field tests conducted in an area of high-podoconiosis prevalence in Southern Ethiopia. The system has five stages according to proximal spread of disease and presence of dermal nodules, ridges and bands. We measured the 1-week repeatability and the inter-observer agreement of the final staging system. The five-stage system is readily understood by community workers with little health training. Kappa for 1-week repeatability was 0.88 (95% CI 0.80-0.96), for agreement between health professionals was 0.71 (95% CI 0.60-0.82), while that between health professionals and community podoconiosis agents without formal health training averaged 0.64 (95% CI 0.52-0.78). This simple staging system with good inter-observer agreement and repeatability can assist in the management and further study of podoconiosis.

Surgical management and outcome of locoregional neuroblastoma: comparison of the Childrens Cancer Group and the international staging systems.

PubMed

Haase, G M; Atkinson, J B; Stram, D O; Lukens, J N; Matthay, K K

1995-02-01

Although precise anatomic staging is prognostically important in neuroblastoma, most widely employed staging systems remain incompatible. The International Neuroblastoma Staging System (INSS) was formulated to incorporate the basic elements of several systems to and define the significance of tumor resectability, anatomic "midline," and lymph node involvement. The authors sought to determine the applicability and value of the INSS compared with the classic Evans system. Between 1980 and 1992, 424 children with the diagnosis of local or regional neuroblastoma were entered in Childrens Cancer Group (CCG) clinical trials. The patients were assigned to Evans stage I, II, or III, by clinical and surgicopathologic assessment, and were treated uniformly by Group-wide therapy protocols. INSS stage 1, 2A, 2B, or 3, was applied, by retrospective analysis, to the children in the earlier studies, and by prospective evaluation of recent patients in the current studies. Survival and relapse-free survival (RFS) rates were determined and compared, based on age at diagnosis, extent of resection, and staging reassignment. All 87 Evans stage I patients were classified as INSS stage 1 and had a 92% 3-year RFS rate. Of the 144 Evans stage II patients, 65 also qualified as INSS stage 1 patients, with an 82% RFS rate. The other 79 stage II children remained in INSS stage 2A or 2B and had a 70% RFS rate (P = .10). Of the 193 Evans stage III patients, 24 were reassigned to INSS stage 1 (85% RFS rate) and 33 to stage 2A or 2B (65% survival rate; 61% RFS rate).(ABSTRACT TRUNCATED AT 250 WORDS)

Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

ClinicalTrials.gov

2017-07-10

Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

[Staging gastritis with the OLGA system: prevalence of advanced stages of gastric atrophy in Mexican patients].

PubMed

Ramírez-Mendoza, P; Ruiz-Castillo, S A; Maroun-Marun, C; Trujillo-Benavides, O; Baltazar-Montúfar, P; Méndez del Monte, R; Angeles-Garay, U

2011-01-01

Gastric adenocarcinoma of intestinal type is preceded by inflammation, which produces mucosal atrophy and intestinal metaplasia, progressing eventually to dysplasia and invasive cancer. Recently an international group, the Operative Link on Gastritis Assessment (OLGA) proponed a staging system for gastric biopsies. To recognize the distribution of advanced stages of gastric mucosal atrophy in Mexican patients with dyspepsia according to the OLGA system. We apply the OLGA system for cancer risk (Stages 0 to IV) to 322 gastric biopsies from consecutive patients with dyspepsia. Using the Sydney protocol, we recorded the presence of atrophy, dysplasia and the relationship with ulcer disease. We report the stage of atrophy for each region and the Helicobacter pylori infection status. We documented 72 (22.4%) cases with atrophy, 50 of them (69.4%) were metaplastic-type. Overall, nine biopsies (2.78%) were stage III (all of them with metaplastic-type atrophy) and there was not stage IV cases. We did not find high-grade dysplasia or intramucosal carcinoma. In 8 of subjects with stage III, we observed low-grade dysplasia. We documented gastric ulcer in 5 patients with stage II, 60% of them with associated low-grade dysplasia. Five patients with duodenal ulcer were found in stages 0 and I. We found low prevalence of advanced stages of mucosal gastric atrophy among patients with dyspepsia. However we recognized 9 patients with stage III according to OLGA system worthy of follow-up because the high risk for developing gastric cancer.

Two-stage earth-to-orbit vehicles with dual-fuel propulsion in the Orbiter

NASA Technical Reports Server (NTRS)

Martin, J. A.

1982-01-01

Earth-to-orbit vehicle studies of future replacements for the Space Shuttle are needed to guide technology development. Previous studies that have examined single-stage vehicles have shown advantages for dual-fuel propulsion. Previous two-stage system studies have assumed all-hydrogen fuel for the Orbiters. The present study examined dual-fuel Orbiters and found that the system dry mass could be reduced with this concept. The possibility of staging the booster at a staging velocity low enough to allow coast-back to the launch site is shown to be beneficial, particularly in combination with a dual-fuel Orbiter. An engine evaluation indicated the same ranking of engines as did a previous single-stage study. Propane and RP-1 fuels result in lower vehicle dry mass than methane, and staged-combustion engines are preferred over gas-generator engines. The sensitivity to the engine selection is less for two-stage systems than for single-stage systems.

A Lymph Node Staging System for Gastric Cancer: A Hybrid Type Based on Topographic and Numeric Systems.

PubMed

Choi, Yoon Young; An, Ji Yeong; Katai, Hitoshi; Seto, Yasuyuki; Fukagawa, Takeo; Okumura, Yasuhiro; Kim, Dong Wook; Kim, Hyoung-Il; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon

2016-01-01

Although changing a lymph node staging system from an anatomically based system to a numerically based system in gastric cancer offers better prognostic performance, several problems can arise: it does not offer information on the anatomical extent of disease and cannot represent the extent of lymph node dissection. The purpose of this study was to discover an alternative lymph node staging system for gastric cancer. Data from 6025 patients who underwent gastrectomy for primary gastric cancer between January 2000 and December 2010 were reviewed. The lymph node groups were reclassified into lesser-curvature, greater-curvature, and extra-perigastric groups. Presence of any metastatic lymph node in one group was considered positive. Lymph node groups were further stratified into four (new N0-new N3) according to the number of positive lymph node groups. Survival outcomes with this new N staging were compared with those of the current TNM system. For validation, two centers in Japan (large center, n = 3443; medium center, n = 560) were invited. Even among the same pN stages, the more advanced new N stage showed worse prognosis, indicating that the anatomical extent of metastatic lymph nodes is important. The prognostic performance of the new staging system was as good as that of the current TNM system for overall advanced gastric cancer as well as lymph node-positive gastric cancer (Harrell C-index was 0.799, 0.726, and 0.703 in current TNM and 0.799, 0.727, and 0.703 in new TNM stage). Validation sets supported these outcomes. The new N staging system demonstrated prognostic performance equal to that of the current TNM system and could thus be used as an alternative.

Effect of ammoniacal nitrogen on one-stage and two-stage anaerobic digestion of food waste.

PubMed

Ariunbaatar, Javkhlan; Scotto Di Perta, Ester; Panico, Antonio; Frunzo, Luigi; Esposito, Giovanni; Lens, Piet N L; Pirozzi, Francesco

2015-04-01

This research compares the operation of one-stage and two-stage anaerobic continuously stirred tank reactor (CSTR) systems fed semi-continuously with food waste. The main purpose was to investigate the effects of ammoniacal nitrogen on the anaerobic digestion process. The two-stage system gave more reliable operation compared to one-stage due to: (i) a better pH self-adjusting capacity; (ii) a higher resistance to organic loading shocks; and (iii) a higher conversion rate of organic substrate to biomethane. Also a small amount of biohydrogen was detected from the first stage of the two-stage reactor making this system attractive for biohythane production. As the digestate contains ammoniacal nitrogen, re-circulating it provided the necessary alkalinity in the systems, thus preventing an eventual failure by volatile fatty acids (VFA) accumulation. However, re-circulation also resulted in an ammonium accumulation, yielding a lower biomethane production. Based on the batch experimental results the 50% inhibitory concentration of total ammoniacal nitrogen on the methanogenic activities was calculated as 3.8 g/L, corresponding to 146 mg/L free ammonia for the inoculum used for this research. The two-stage system was affected by the inhibition more than the one-stage system, as it requires less alkalinity and the physically separated methanogens are more sensitive to inhibitory factors, such as ammonium and propionic acid. Copyright © 2014 Elsevier Ltd. All rights reserved.

A pragmatic clinicopathobiological grouping/staging system for gliomas: proposal of the Indian TNM subcommittee on brain tumors.

PubMed

Gupta, Tejpal; Sarin, Rajiv; Jalali, Rakesh; Sharma, Suash; Kurkure, Purna; Goel, Atul

2009-01-01

There is no universally accepted staging system for primary brain tumors wherein prognostication is mainly based on complex composite indices. To develop a simple, pragmatic, and widely applicable grouping/staging system for gliomas, the most common primary brain tumor. An expert neurooncology panel with representation from radiation oncology, neurosurgery, pathology, radiology, and medical oncology had several rounds of discussion on issues pertinent to brain tumor staging. The trade off was between the accuracy of prognostic categorization and a pragmatic, widely applicable approach. The Tumor-Node-Metastasis staging was considered irrelevant for gliomas that seldom metastasize to lymphatics or outside the neuraxis. Instead, a 4-point staging/grouping system is proposed, using histological grade as the main prognostic variable and at least one stage migration based on other unfavorable features such as tumor location (brainstem); age (<5 years for all grades, >50 years for high-grade, and >40 years for low-grade gliomas); poor neurological performance status (NPS 2-4); multicentricity and/or gliomatosis; and adverse biological parameters (proliferative index, angiogenesis markers, apoptotic index, cytogenetic abnormalities, and molecular markers). In absence of a grouping/staging system for primary brain tumors, prognostification is mostly based on complex composite indices. The proposed clinicopathobiological grouping/staging system for gliomas is a simple, pragmatic, and user-friendly tool with a potential to fulfill the objectives of staging classification.

CONSECUTIVE SYSTEMS GUIDANCE MANUAL FOR THE STAGE 2 DISINFECTION BYPRODUCT RULE (DBPR)

EPA Science Inventory

Description: This manual discusses requirements for consecutive systems (public water systems that receive fully treated water from other public water systems) to comply with Stage 2 DBPR monitoring and MCLs. Most previous drinking water rules, including the Stage 1 DBPR, have no...

Prognostic Impact of the 6th and 7th American Joint Committee on Cancer TNM Staging Systems on Esophageal Cancer Patients Treated With Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nomura, Motoo, E-mail: excell@hkg.odn.ne.jp; Department of Radiation Oncology, Aichi Cancer Center Hospital; Shitara, Kohei

2012-02-01

Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of themore » 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.« less

Performance enhancement of existing two-stage sounding rocket vehicles through the use of tandem booster systems

NASA Technical Reports Server (NTRS)

Flores, C. C.; Gurkin, L. W.

1982-01-01

The three-stage Taurus-Nike-Tomahawk launch vehicle is being considered for performance enhancement of the existing Taurus-Tomahawk flight system. In addition, performance enhancement of other existing two-stage launch vehicles is being considered through the use of tandem booster systems. Aeroballistic characteristics of the proposed Taurus-Nike-Tomahawk vehicle are presented, as are overall performance capabilities of other potential three-stage flight systems.

Higher Numbers of T-Bet+ Tumor-Infiltrating Lymphocytes Associate with Better Survival in Human Epithelial Ovarian Cancer.

PubMed

Xu, Yun; Chen, Lujun; Xu, Bin; Xiong, Yuqi; Yang, Min; Rui, Xiaohui; Shi, Liangrong; Wu, Changping; Jiang, Jingting; Lu, Binfeng

2017-01-01

T-bet, a member of the T-box family of transcription factors, is a key marker of type I immune response within the tumor microenvironment, and has been previously reported by us to serve as an important prognostic indicator for human gastric cancer patients and a potential biomarker for immunotherapy. In the present study, we aimed to assess the clinical significance and prognostic value of T-bet+ tumor-infiltrating lymphocytes in human epithelial ovarian cancer. The immunohistochemistry was used to analyze the infiltration density of T-bet+ lymphoid cells in human epithelial ovarian cancer tissues, and the flow cytometry analysis was used to further analyze the presence of T-bet+ tumor-infiltrating lymphocytes subgroups in cancer tissues. Our immunohistochemistry analysis showed increased number of T-bet+ lymphoid cells in the human epithelial ovarian cancer tissues, and the flow cytometry analysis further demonstrated the presence of T-bet+ tumor-infiltrating lymphocytes subgroups including CD4+ , CD8+ T cells and NK cells. In addition, we also observed a significant association of T-bet+ tumor-infiltrating lymphocytes density in the tumor nest of cancer with not only serum CA125 levels but also with distant metastasis. However no association was observed with other characteristics like patients' age, pathological type, FIGO stage, tumor site and tumor size. Furthermore, the survival analysis showed that higher density of T-bet+ tumor-infiltrating lymphocytes both in tumor nest and tumor stroma of cancer tissues was significantly associated with better patient survival. In addition, the density of T-bet+ tumor-infiltrating lymphocytes in tumor nest appeared to be an independent risk factor for predicting patients' postoperative prognoses. Our data indicated that the key transcription factor T-bet might play an important role in the type I immune cells mediated antitumor response, and the density of T-bet+ lymphocytes in human epithelial ovarian cancer tissues could serve as a prognostic predictor for ovarian cancer patients. © 2017 The Author(s)Published by S. Karger AG, Basel.

SU-E-T-157: Evaluation and Comparison of Doses to Pelvic Lymph Nodes and to Point B with 3D Image Guided Treatment Planning for High Dose Brachytherapy for Treatment of Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhandare, N.

2014-06-01

Purpose: To estimate and compare the doses received by the obturator, external and internal iliac lymph nodes and point Methods: CT-MR fused image sets of 15 patients obtained for each of 5 fractions of HDR brachytherapy using tandem and ring applicator, were used to generate treatment plans optimized to deliver a prescription dose to HRCTV-D90 and to minimize the doses to organs at risk (OARs). For each set of image, target volume (GTV, HRCTV) OARs (Bladder, Rectum, Sigmoid), and both left and right pelvic lymph nodes (obturator, external and internal iliac lymph nodes) were delineated. Dose-volume histograms (DVH) were generatedmore » for pelvic nodal groups (left and right obturator group, internal and external iliac chains) Per fraction DVH parameters used for dose comparison included dose to 100% volume (D100), and dose received by 2cc (D2cc), 1cc (D1cc) and 0.1 cc (D0.1cc) of nodal volume. Dose to point B was compared with each DVH parameter using 2 sided t-test. Pearson correlation were determined to examine relationship of point B dose with nodal DVH parameters. Results: FIGO clinical stage varied from 1B1 to IIIB. The median pretreatment tumor diameter measured on MRI was 4.5 cm (2.7– 6.4cm).The median dose to bilateral point B was 1.20 Gy ± 0.12 or 20% of the prescription dose. The correlation coefficients were all <0.60 for all nodal DVH parameters indicating low degree of correlation. Only 2 cc of obturator nodes was not significantly different from point B dose on t-test. Conclusion: Dose to point B does not adequately represent the dose to any specific pelvic nodal group. When using image guided 3D dose-volume optimized treatment nodal groups should be individually identified and delineated to obtain the doses received by pelvic nodes.« less

BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer.

PubMed

Wieser, Verena; Gaugg, Inge; Fleischer, Martina; Shivalingaiah, Giridhar; Wenzel, Soeren; Sprung, Susanne; Lax, Sigurd F; Zeimet, Alain G; Fiegl, Heidelinde; Marth, Christian

2018-04-03

Checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand PD-L1 are critically required for tumor immune escape. The objective of this study was to investigate tumoral PD-1 and PD-L1 mRNA-expression in a cohort of ovarian cancer (OC) patients in relation to tumor mutations. We analyzed mRNA expression of PD-1 , PD-L1 and IFNG by quantitative real-time PCR in tissue of 170 patients with low grade-serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non-diseased tissues (ovaries and fallopian tubes) in relation to tumor protein 53 ( TP53 ) and breast cancer gene 1/2 ( BRCA1/2 ) mutation status. TP53 -mutated OC strongly expressed PD-L1 compared to TP53 wild-type OC ( p = 0.028) and BRCA1/2 -mutated OC increasingly expressed PD-1 ( p = 0.024) and PD-L1 ( p = 0.012) compared to BRCA1/2 wild-type OC. For the first time in human, we noted a strong correlation between tumoral IFNG and PD-1 or PD-L1 mRNA-expression, respectively ( p < 0.001). OC tissue increasingly expressed PD-1 compared to healthy controls (vs. ovaries: p < 0.001; vs. tubes: p = 0.018). PD-1 and PD-L1 mRNA-expression increased with higher tumor grade ( p = 0.008 and p = 0.027, respectively) and younger age (< median age, p = 0.001). Finally, in the major subgroup of our cohort, FIGO stage III/IV HGSOC, high PD-1 and PD-L1 mRNA-expression was associated with reduced progression-free ( p = 0.024) and overall survival ( p = 0.049) but only in the univariate analysis. Our study suggests that in OC PD-1 / PD-L1 mRNA-expression is controlled by IFNγ and affected by TP53 and BRCA1/2 mutations. We suggest that these mutations might serve as potential predictive factors that guide anti- PD1 / PD-L1 immunotherapy.

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.

PubMed

Levitchi, Mihai; Charra-Brunaud, Claire; Quetin, Philippe; Haie-Meder, Christine; Kerr, Christine; Castelain, Bernard; Delannes, Martine; Thomas, Laurence; Desandes, Emmanuel; Peiffert, Didier

2012-06-01

To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(β)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(β)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity. For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas.

PubMed

Nakayama, Kentaro; Rahman, Mohammed Tanjimur; Rahman, Munmun; Nakamura, Kohei; Ishikawa, Masako; Katagiri, Hiroshi; Sato, Emi; Ishibashi, Tomoka; Iida, Kouji; Ishikawa, Noriyuki; Kyo, Satoru

2016-02-01

The clinicopathological significance of amplification was investigated of the gene encoding cyclin E (CCNE1) and we assessed whether CCNE1 was a potential target in endometrioid endometrial carcinomas. CCNE1 amplification and CCNE1 or F-box and WD repeat domain-containing 7 (FBXW7) expression in endometrial endometrioid carcinoma was assessed by immunohistochemistry and fluorescence in situ hybridization. CCNE1 knockdown by small interfering RNA (siRNA) was used to assess the CCNE1 function. The results showed that CCNE1 amplification was present in 9 (8.3%) of 108 endometrial carcinomas. CCNE1 amplification was correlated with high histological grade (Grade 3; p=0.0087) and lymphovascular space invasion (p=0.0258). No significant association was observed between CCNE1 amplification and FIGO stage (p=0.851), lymph node metastasis (p=0.078), body mass index (p=0.265), deep myometrial invasion (p=0.256), menopausal status (p=0.289) or patient age (p=0.0817). CCNE1 amplification was significantly correlated with shorter progression-free and overall survival (p=0.0081 and 0.0073, respectively). CCNE1 protein expression or loss of FBXW7 expression in endometrial endometrioid carcinoma tended to be correlated with shorter progression-free and overall survival; however, this difference was not statistically significant. Multivariate analysis showed that CCNE1 amplification was an independent prognostic factor for overall survival but not for progression-free survival (P=0.0454 and 0.2175, respectively). Profound growth inhibition was observed in siRNA-transfected cancer cells with endogenous CCNE1 overexpression compared with that in cancer cells having low CCNE1 expression. CCNE1 amplification was independent of p53, HER2, MLH1 and ARID1A expression but dependent on PTEN expression in endometrial carcinomas. These findings indicated that CCNE1 amplification was critical for the survival of endometrial endometrioid carcinomas. Furthermore, the effects of CCNE1 knockdown were dependent on the CCNE1 expression status, suggesting that CCNE1-targeted therapy may be beneficial for patients with endometrial endometrioid carcinoma having CCNE1 amplification.

CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas

PubMed Central

NAKAYAMA, KENTARO; RAHMAN, MOHAMMED TANJIMUR; RAHMAN, MUNMUN; NAKAMURA, KOHEI; ISHIKAWA, MASAKO; KATAGIRI, HIROSHI; SATO, EMI; ISHIBASHI, TOMOKA; IIDA, KOUJI; ISHIKAWA, NORIYUKI; KYO, SATORU

2016-01-01

The clinicopathological significance of amplification was investigated of the gene encoding cyclin E (CCNE1) and we assessed whether CCNE1 was a potential target in endometrioid endometrial carcinomas. CCNE1 amplification and CCNE1 or F-box and WD repeat domain-containing 7 (FBXW7) expression in endometrial endometrioid carcinoma was assessed by immunohistochemistry and fluorescence in situ hybridization. CCNE1 knockdown by small interfering RNA (siRNA) was used to assess the CCNE1 function. The results showed that CCNE1 amplification was present in 9 (8.3%) of 108 endometrial carcinomas. CCNE1 amplification was correlated with high histological grade (Grade 3; P=0.0087) and lymphovascular space invasion (P=0.0258). No significant association was observed between CCNE1 amplification and FIGO stage (P=0.851), lymph node metastasis (P=0.078), body mass index (P=0.265), deep myometrial invasion (P=0.256), menopausal status (P=0.289) or patient age (P=0.0817). CCNE1 amplification was significantly correlated with shorter progression-free and overall survival (P=0.0081 and 0.0073, respectively). CCNE1 protein expression or loss of FBXW7 expression in endometrial endometrioid carcinoma tended to be correlated with shorter progression-free and overall survival; however, this difference was not statistically significant. Multivariate analysis showed that CCNE1 amplification was an independent prognostic factor for overall survival but not for progression-free survival (P=0.0454 and 0.2175, respectively). Profound growth inhibition was observed in siRNA-transfected cancer cells with endogenous CCNE1 overexpression compared with that in cancer cells having low CCNE1 expression. CCNE1 amplification was independent of p53, HER2, MLH1 and ARID1A expression but dependent on PTEN expression in endometrial carcinomas. These findings indicated that CCNE1 amplification was critical for the survival of endometrial endometrioid carcinomas. Furthermore, the effects of CCNE1 knockdown were dependent on the CCNE1 expression status, suggesting that CCNE1-targeted therapy may be beneficial for patients with endometrial endometrioid carcinoma having CCNE1 amplification. PMID:26647729

Temporal analysis of intratumoral metabolic heterogeneity characterized by textural features in cervical cancer.

PubMed

Yang, Fei; Thomas, Maria A; Dehdashti, Farrokh; Grigsby, Perry W

2013-05-01

The aim of this pilot study was to explore heterogeneity in the temporal behavior of intratumoral [(18)F]fluorodeoxyglucose (FDG) accumulation at a regional scale in patients with cervical cancer undergoing chemoradiotherapy. Included in the study were 20 patients with FIGO stages IB1 to IVA cervical cancer treated with combined chemoradiotherapy. Patients underwent FDG PET/CT before treatment, during weeks 2 and 4 of treatment, and 12 weeks after completion of therapy. Patients were classified based on response to therapy as showing a complete metabolic response (CMR), a partial metabolic response (PMR), or residual disease and the development of new disease (NEW). Based on the presence of residual primary tumor following therapy, patients were divided into two groups, CMR and PMR/NEW. Temporal profiles of intratumoral FDG heterogeneity as characterized by textural features at a regional scale were assessed and compared with those of the standardized uptake value (SUV) indices (SUVmax and SUVmean) within the context of differentiating response groups. Textural features at a regional scale with emphasis on characterizing contiguous regions of high uptake in tumors decreased significantly with time (P < 0.001) in the CMR group, while features describing contiguous regions of low uptake along with those measuring the nonuniformity of contiguous isointense regions in tumors exhibited significant temporal changes in the PMR/NEW group (P < 0.03) but showed no persistent trends with time. Both SUV indices showed significant changes during the course of the disease in both patient groups (P < 0.001 for SUVmax and SUVmean in the CMR group; P = 0.0109 and 0.0136, respectively, for SUVmax and SUVmean in the PMR/NEW group), and also decreased at a constant rate in the CMR group and decreased up to the 4th week of treatment and then increased in the PMR/NEW group. The temporal changes in the heterogeneity of intratumoral FDG distribution characterized at a regional scale using image-based textural features may provide an adjunctive or alternative option for understanding tumor response to chemoradiotherapy and interpreting FDG accumulation dynamics in patients with malignant cervical tumors during the course of the disease.

Prediction of outcome using pretreatment 18F-FDG PET/CT and MRI radiomics in locally advanced cervical cancer treated with chemoradiotherapy.

PubMed

Lucia, François; Visvikis, Dimitris; Desseroit, Marie-Charlotte; Miranda, Omar; Malhaire, Jean-Pierre; Robin, Philippe; Pradier, Olivier; Hatt, Mathieu; Schick, Ulrike

2018-05-01

The aim of this study is to determine if radiomics features from 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) images could contribute to prognoses in cervical cancer. One hundred and two patients (69 for training and 33 for testing) with locally advanced cervical cancer (LACC) receiving chemoradiotherapy (CRT) from 08/2010 to 12/2016 were enrolled in this study. 18 F-FDG PET/CT and MRI examination [T1, T2, T1C, diffusion-weighted imaging (DWI)] were performed for each patient before CRT. Primary tumor volumes were delineated with the fuzzy locally adaptive Bayesian algorithm in the PET images and with 3D Slicer™ in the MRI images. Radiomics features (intensity, shape, and texture) were extracted and their prognostic value was compared with clinical parameters for recurrence-free and locoregional control. In the training cohort, median follow-up was 3.0 years (range, 0.43-6.56 years) and relapse occurred in 36% of patients. In univariate analysis, FIGO stage (I-II vs. III-IV) and metabolic response (complete vs. non-complete) were probably associated with outcome without reaching statistical significance, contrary to several radiomics features from both PET and MRI sequences. Multivariate analysis in training test identified Grey Level Non Uniformity GLRLM in PET and Entropy GLCM in ADC maps from DWI MRI as independent prognostic factors. These had significantly higher prognostic power than clinical parameters, as evaluated in the testing cohort with accuracy of 94% for predicting recurrence and 100% for predicting lack of loco-regional control (versus ~50-60% for clinical parameters). In LACC treated with CRT, radiomics features such as EntropyGLCM and GLNUGLRLM from functional imaging DWI-MRI and PET, respectively, are independent predictors of recurrence and loco-regional control with significantly higher prognostic power than usual clinical parameters. Further research is warranted for their validation, which may justify more aggressive treatment in patients identified with high probability of recurrence.

NASA Ares I Launch Vehicle Roll and Reaction Control Systems Design Status

NASA Technical Reports Server (NTRS)

Butt, Adam; Popp, Chris G.; Pitts, Hank M.; Sharp, David J.

2009-01-01

This paper provides an update of design status following the preliminary design review of NASA s Ares I first stage roll and upper stage reaction control systems. The Ares I launch vehicle has been chosen to return humans to the moon, mars, and beyond. It consists of a first stage five segment solid rocket booster and an upper stage liquid bi-propellant J-2X engine. Similar to many launch vehicles, the Ares I has reaction control systems used to provide the vehicle with three degrees of freedom stabilization during the mission. During launch, the first stage roll control system will provide the Ares I with the ability to counteract induced roll torque. After first stage booster separation, the upper stage reaction control system will provide the upper stage element with three degrees of freedom control as needed. Trade studies and design assessments conducted on the roll and reaction control systems include: propellant selection, thruster arrangement, pressurization system configuration, and system component trades. Since successful completion of the preliminary design review, work has progressed towards the critical design review with accomplishments made in the following areas: pressurant / propellant tank, thruster assembly, and other component configurations, as well as thruster module design, and waterhammer mitigation approach. Also, results from early development testing are discussed along with plans for upcoming system testing. This paper concludes by summarizing the process of down selecting to the current baseline configuration for the Ares I roll and reaction control systems.

The Prognostic Value of the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging System in HER2-Enriched Subtype Breast Cancer, a Retrospective Analysis.

PubMed

Zhou, Bin; Xu, Ling; Ye, Jingming; Xin, Ling; Duan, Xuening; Liu, Yinhua

2017-08-01

The American Joint Committee on Cancer (AJCC) released its 8th edition of tumor staging which is to be implemented in early 2018. The present study aimed to analyze the prognostic value of AJCC 8th edition Cancer Staging System in HER2-enriched breast cancer, on a retrospective cohort. This study was a retrospective single-center study of HER2-enriched breast cancer cases diagnosed from January 2008 to December 2014. Clinicopathological features and follow up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore prognostic factors for disease outcome. We restaged patients based on the 8th edition of the AJCC cancer staging system and analyzed prognostic value of the Anatomic Stage Group and the Prognostic Stage Group. The study enrolled 170 HER2-enriched subtype breast cancer patients with 5-year disease free survival (DFS) of 85.1% and 5-year overall survival (OS) of 86.8%. Prognostic stages of 117 cases (68.8%) changed compared with anatomic stages, with 116 upstaged cases and 1 downstaged case. The Anatomic Stage Groups had a significant prognostic impact on DFS (χ 2 =16.752, p<0.001) and OS (χ 2 =25.038, p<0.001). The Prognostic Staging Groups had a significant prognostic impact on DFS (χ 2 =6.577, p=0.037) and OS (χ 2 =21.762, p<0.001). In the multivariate analysis, both stage groups were independent predictors of OS. Both Anatomic and Prognostic Stage Groups in the 8th edition of the AJCC breast cancer staging system had prognostic value in HER2-enriched subtype breast cancer. The Prognostic Stage system was a breakthrough on the basis of anatomic staging system. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

A randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats.

PubMed

Peacock, Rachel E; Hosgood, Giselle; Swindells, Katrin L; Smart, Lisa

2015-01-01

To assess for any clinical benefit of intravenous lipid emulsion (ILE) for permethrin toxicosis in cats by comparing the progression of clinical signs of cats before and after treatment with ILE to cats treated with a saline control. To accomplish this objective, a clinical staging system for cats with permethrin toxicosis was developed and validated. Prospective, multicenter, randomized, controlled clinical trial. University veterinary teaching hospital and 12 private veterinary emergency hospitals. Thirty-four client-owned cats with permethrin toxicosis. A clinical staging system was designed based on abnormalities found on physical examination of cats with permethrin toxicosis. The clinical staging system had 6 stages, ranging from Stage A for cats with no abnormalities to Stage F for cats with grand mal seizures. The system was validated for intraviewer and interviewer variability. Cats in the clinical trial were randomized to receive 15 mL/kg of either intravenous 0.9% saline (control) or 20% ILE over 60 minutes. For each cat, a clinical stage was recorded at set time points before and after the randomized treatment was administered. The distribution of clinical stage stratified over time was compared across treatment groups. The clinical staging system showed excellent repeatability (P = 1.0) and reliability (P = 1.0). In the clinical trial, there was a significant difference in the distribution of clinical stages over time (P < 0.001) and from presentation stage to Stage B (P = 0.006), with ILE-treated cats (n = 20) having lower clinical stages earlier than control cats (n = 14). There was no significant difference in signalment, body weight, or supportive treatment between the groups. The clinical staging system was repeatable and reliable. Clinical stages of permethrin toxicosis in ILE-treated cats improved earlier compared to control cats, suggesting ILE may be a useful adjunctive therapy in the treatment of permethrin toxicosis in cats. © Veterinary Emergency and Critical Care Society 2015.

Proposed Staging System for Patients With HPV-Related Oropharyngeal Cancer Based on Nasopharyngeal Cancer N Categories

PubMed Central

Dahlstrom, Kristina R.; Garden, Adam S.; William, William N.; Lim, Ming Yann

2016-01-01

Purpose Patients with human papillomavirus (HPV)–related oropharyngeal cancer (OPC) generally present with more advanced disease but have better survival than patients with HPV-unrelated OPC. The current American Joint Commission on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system for OPC was developed for HPV-unrelated OPC. A new staging system is needed to adequately predict outcomes of patients with HPV-related OPC. Patients and Methods Patients with newly diagnosed HPV-positive OPC (by p16 immunohistochemistry or in situ hybridization) treated at our institution from January 2003 through December 2012 were included. By using recursive partitioning analysis (RPA), we developed new stage groupings with both traditional OPC regional lymph node (N) categories and nasopharyngeal carcinoma (NPC) N categories. Survival was estimated by the Kaplan-Meier method, and the relationship between stage and survival was examined by using Cox proportional hazards regression analysis. Results A total of 661 patients with HPV-positive OPC met the inclusion criteria. With the traditional TNM staging system, there was no difference in survival between stages (P = .141). RPA with NPC N categories resulted in more balanced stage groups and better separation between groups for 5-year survival than RPA with traditional OPC N categories. With the stage groupings that were based in part on NPC N categories, the risk of death increased with increasing stage (P for trend < .001), and patients with stage III disease had five times the risk of death versus patients with stage IA disease. Conclusion New stage groupings that are based on primary tumor (T) categories and NPC N categories better separate patients with HPV-positive OPC with respect to survival than does the current AJCC/UICC TNM staging system. Although confirmation of our findings in other patient populations is needed, we propose consideration of NPC N categories as an alternative to the traditional OPC N categories in the new AJCC/UICC TNM staging system that is currently being developed. PMID:26884553

Evaluation of Sixth Edition of AJCC Staging System for Nasopharyngeal Carcinoma and Proposed Improvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Mengzhong; Tang Linglong; Zong Jingfeng

2008-03-15

Purpose: To evaluate the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma and to search for ways to improve the system. Methods and Materials: We performed a retrospective review of data from 749 biopsy-proven nonmetastatic nasopharyngeal carcinoma patients. All patients had undergone contrast-enhanced computed tomography and had received radiotherapy as their primary treatment. Results: The T stage, N stage, and stage group were significant, independent predictors for disease-specific death. No significant differences were found between Stage T2a and T1 in local failure-free survival or between Stage N3a and N2 in distantmore » failure-free survival. Survival curves of the different T/N subsets showed a better segregation when T2a and N3a were downstaged to T1 and N2, respectively. The hazard ratio of disease-specific deaths for patients with T2N0 disease was similar to that of patients with T1N0 disease; the same result was found for the T3N0 and T4N0 subsets. Downstaging the T2N0 subset to Stage I, T3N0 to Stage II, and T4N0 to Stage III resulted in a more balanced patient distribution, better hazard consistency among subgroups, and improved hazard discrimination between overall stages. Conclusion: Using the 6th edition of the American Joint Committee on Cancer staging system produced an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorization of the T, N, and group stage criteria.« less

Advanced Launch Vehicle Upper Stages Using Liquid Propulsion and Metallized Propellants

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan A.

1990-01-01

Metallized propellants are liquid propellants with a metal additive suspended in a gelled fuel or oxidizer. Typically, aluminum (Al) particles are the metal additive. These propellants provide increase in the density and/or the specific impulse of the propulsion system. Using metallized propellant for volume-and mass-constrained upper stages can deliver modest increases in performance for low earth orbit to geosynchronous earth orbit (LEO-GEO) and other earth orbital transfer missions. Metallized propellants, however, can enable very fast planetary missions with a single-stage upper stage system. Trade studies comparing metallized propellant stage performance with non-metallized upper stages and the Inertial Upper Stage (IUS) are presented. These upper stages are both one- and two-stage vehicles that provide the added energy to send payloads to altitudes and onto trajectories that are unattainable with only the launch vehicle. The stage designs are controlled by the volume and the mass constraints of the Space Transportation System (STS) and Space Transportation System-Cargo (STS-C) launch vehicles. The influences of the density and specific impulse increases enabled by metallized propellants are examined for a variety of different stage and propellant combinations.

Analysis of effects of a new environmental pollutant, bisphenol A, on antioxidant systems in soybean roots at different growth stages

NASA Astrophysics Data System (ADS)

Zhang, Jiazhi; Li, Xingyi; Zhou, Li; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2016-03-01

Bisphenol A (BPA) is an important industrial raw material. Because of its widespread use and increasing release into environment, BPA has become a new environmental pollutant. Previous studies about BPA’s effects in plants focus on a certain growth stage. However, the plant’s response to pollutants varies at different growth stages. Therefore, in this work, BPA’s effects in soybean roots at different growth stages were investigated by determining the reactive oxygen species levels, membrane lipid fatty acid composition, membrane lipid peroxidation, and antioxidant systems. The results showed that low-dose BPA exposure slightly caused membrane lipid peroxidation but didn’t activate antioxidant systems at the seedling stage, and this exposure did not affect above process at other growth stages; high-dose BPA increased reactive oxygen species levels and then caused membrane lipid peroxidation at all growth stages although it activated antioxidant systems, and these effects were weaker with prolonging the growth stages. The recovery degree after withdrawal of BPA exposure was negatively related to BPA dose, but was positively related to growth stage. Taken together, the effects of BPA on antioxidant systems in soybean roots were associated with BPA exposure dose and soybean growth stage.

Analysis of effects of a new environmental pollutant, bisphenol A, on antioxidant systems in soybean roots at different growth stages

PubMed Central

Zhang, Jiazhi; Li, Xingyi; Zhou, Li; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2016-01-01

Bisphenol A (BPA) is an important industrial raw material. Because of its widespread use and increasing release into environment, BPA has become a new environmental pollutant. Previous studies about BPA’s effects in plants focus on a certain growth stage. However, the plant’s response to pollutants varies at different growth stages. Therefore, in this work, BPA’s effects in soybean roots at different growth stages were investigated by determining the reactive oxygen species levels, membrane lipid fatty acid composition, membrane lipid peroxidation, and antioxidant systems. The results showed that low-dose BPA exposure slightly caused membrane lipid peroxidation but didn’t activate antioxidant systems at the seedling stage, and this exposure did not affect above process at other growth stages; high-dose BPA increased reactive oxygen species levels and then caused membrane lipid peroxidation at all growth stages although it activated antioxidant systems, and these effects were weaker with prolonging the growth stages. The recovery degree after withdrawal of BPA exposure was negatively related to BPA dose, but was positively related to growth stage. Taken together, the effects of BPA on antioxidant systems in soybean roots were associated with BPA exposure dose and soybean growth stage. PMID:27030053

Two stage sorption type cryogenic refrigerator including heat regeneration system

NASA Technical Reports Server (NTRS)

Jones, Jack A. (Inventor); Wen, Liang-Chi (Inventor); Bard, Steven (Inventor)

1989-01-01

A lower stage chemisorption refrigeration system physically and functionally coupled to an upper stage physical adsorption refrigeration system is disclosed. Waste heat generated by the lower stage cycle is regenerated to fuel the upper stage cycle thereby greatly improving the energy efficiency of a two-stage sorption refrigerator. The two stages are joined by disposing a first pressurization chamber providing a high pressure flow of a first refrigerant for the lower stage refrigeration cycle within a second pressurization chamber providing a high pressure flow of a second refrigerant for the upper stage refrigeration cycle. The first pressurization chamber is separated from the second pressurization chamber by a gas-gap thermal switch which at times is filled with a thermoconductive fluid to allow conduction of heat from the first pressurization chamber to the second pressurization chamber.

Lunar lander and return propulsion system trade study

NASA Technical Reports Server (NTRS)

Hurlbert, Eric A.; Moreland, Robert; Sanders, Gerald B.; Robertson, Edward A.; Amidei, David; Mulholland, John

1993-01-01

This trade study was initiated at NASA/JSC in May 1992 to develop and evaluate main propulsion system alternatives to the reference First Lunar Outpost (FLO) lander and return-stage transportation system concept. Thirteen alternative configurations were developed to explore the impacts of various combinations of return stage propellants, using either pressure or pump-fed propulsion systems and various staging options. Besides two-stage vehicle concepts, the merits of single-stage and stage-and-a-half options were also assessed in combination with high-performance liquid oxygen and liquid hydrogen propellants. Configurations using an integrated modular cryogenic engine were developed to assess potential improvements in packaging efficiency, mass performance, and system reliability compared to non-modular cryogenic designs. The selection process to evaluate the various designs was the analytic hierarchy process. The trade study showed that a pressure-fed MMH/N2O4 return stage and RL10-based lander stage is the best option for a 1999 launch. While results of this study are tailored to FLO needs, the design date, criteria, and selection methodology are applicable to the design of other crewed lunar landing and return vehicles.

Development and testing of a de novo clinical staging system for podoconiosis (endemic non-filarial elephantiasis)

PubMed Central

Tekola, Fasil; Ayele, Zewdu; HaileMariam, Dereje; Fuller, Claire; Davey, Gail

2010-01-01

Summary Background Podoconiosis (endemic non-filarial elephantiasis) is a geochemical disease in individuals exposed to red-clay soil. Despite the prevalence and public health importance of podoconiosis, there is as yet no accepted clinical staging system. Objective We aimed to develop and test a robust clinical staging system for podoconiosis. Methods We adapted the Dreyer system for staging filarial lymphoedema and tested it in four re-iterative field tests conducted in an area of high podoconiosis prevalence in Southern Ethiopia. The system finally arrived at has five stages according to proximal spread of disease and presence of dermal nodules, ridges and bands. We measured the one-week repeatability and the inter-observer agreement of the final staging system. Results We have developed a five-stage system that is readily understood by community workers with little health training. Kappa for one-week repeatability was 0.88 (95% CI 0.80 to 0.96), Kappa for agreement between health professionals was 0.71 (95% CI 0.60 to 0.82), while that between health professionals and community podoconiosis agents without formal health training averaged 0.64 (95% CI 0.52 to 0.78). Conclusions A simple staging system with good inter-observer agreement and repeatability has been developed to assist in the management and further study of podoconiosis. PMID:18721188

Scoring and staging systems using cox linear regression modeling and recursive partitioning.

PubMed

Lee, J W; Um, S H; Lee, J B; Mun, J; Cho, H

2006-01-01

Scoring and staging systems are used to determine the order and class of data according to predictors. Systems used for medical data, such as the Child-Turcotte-Pugh scoring and staging systems for ordering and classifying patients with liver disease, are often derived strictly from physicians' experience and intuition. We construct objective and data-based scoring/staging systems using statistical methods. We consider Cox linear regression modeling and recursive partitioning techniques for censored survival data. In particular, to obtain a target number of stages we propose cross-validation and amalgamation algorithms. We also propose an algorithm for constructing scoring and staging systems by integrating local Cox linear regression models into recursive partitioning, so that we can retain the merits of both methods such as superior predictive accuracy, ease of use, and detection of interactions between predictors. The staging system construction algorithms are compared by cross-validation evaluation of real data. The data-based cross-validation comparison shows that Cox linear regression modeling is somewhat better than recursive partitioning when there are only continuous predictors, while recursive partitioning is better when there are significant categorical predictors. The proposed local Cox linear recursive partitioning has better predictive accuracy than Cox linear modeling and simple recursive partitioning. This study indicates that integrating local linear modeling into recursive partitioning can significantly improve prediction accuracy in constructing scoring and staging systems.

Revision concepts and distinctive points of the new Japanese classification for biliary tract cancers in comparison with the 7(th) edition of the Union for International Cancer Control and the American Joint Committee on Cancer staging system.

PubMed

Ohtsuka, Masayuki; Miyakawa, Shuichi; Nagino, Masato; Takada, Tadahiro; Miyazaki, Masaru

2015-03-01

The 3(rd) English edition of the Japanese classification of the biliary tract cancers (JC) is now available in this journal. The primary aim of this revision is to provide all clinicians and researchers with a common language of cancer staging at an international level. On the other hand, there are several important issues that should be solved for the optimization of the staging system. Revision concepts and major revision points of the 3(rd) English edition of the JC were reviewed. Furthermore, comparing with the 7(th) edition of staging system developed by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), distinctive points in the JC was discussed. In this edition of the JC, the same stage groupings as those in the UICC/AJCC staging system were basically adopted. T, N, and M categories were also identical in principle with those in the UICC/AJCC staging system, although slight modifications were proposed as the "Japanese rules". As distinctive points, perihilar cholangiocarcinomas and ampullary region carcinomas were clearly defined. Intraepithelial tumor was discriminated from invasive carcinoma at ductal resection margins. Classifications of site-specific surgical margin status remained in this edition. Histological classification was based on that in the former editions of the JC, but adopted some parts of the World Health Organization classification. The JC now share its staging system of the biliary tact carcinomas with the UICC/AJCC staging system. Future validation of the "Japanese rules" could provide important evidence to make globally standardized staging system. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

A retrospective evaluation of furosemide and mannitol for prevention of cisplatin-induced nephrotoxicity.

PubMed

Mach, C M; Kha, C; Nguyen, D; Shumway, J; Meaders, K M; Ludwig, M; Williams-Brown, M Y; Anderson, M L

2017-06-01

Nephrotoxicity is a recognized side effect of cisplatin chemotherapy. However, the optimal strategy for preventing cisplatin-induced nephrotoxicity, if any, remains unclear. The primary objective for this study was to determine whether mannitol or furosemide provides better nephroprotection when administered with hydration prior to weekly, low-dose cisplatin concurrently with whole pelvic radiotherapy. Clinical data were abstracted from all women who underwent chemoradiation for FIGO IB2-IVA cervical cancer at a regional safety net health system between January 2009 and December 2014. Creatinine clearance was estimated using the IDMS-traceable MDRD Study Equation. Descriptive statistics were used to summarize patient demographics. Cox proportional hazard models were used to identify factors associated with hypomagnesemia and survival. A total of 133 women received 656 weekly doses of single-agent cisplatin (40 mg/m 2 ) concomitant with whole pelvic radiation. Furosemide (20 mg) was administered intravenously prior to 341 cisplatin doses, whereas mannitol (24 g) was administered prior to 315 doses. Significant magnesium wasting was observed after the second weekly cisplatin infusion regardless of whether furosemide or mannitol was utilized. Repetitive low-dose cisplatin infusion had no impact on measured levels of serum creatinine or estimated glomerular filtration rate. Prior history of hypertension, diabetes mellitus, hepatitis C infection and acute gastrointestinal toxicity were each associated with early onset of hypomagnesemia. Repetitive administration of low-dose cisplatin concurrent with whole pelvic radiation is associated with magnesium wasting. However, choice of diuretic with pretreatment hydration had no significant impact on the severity of this adverse effect. © 2017 John Wiley & Sons Ltd.

Comprehensive preoperative staging system for endoscopic single and multicorridor approaches to juvenile nasal angiofibromas

PubMed Central

Janakiram, Trichy N.; Sharma, Shilpee B.; Kasper, Ekkehard; Deshmukh, Onkar; Cherian, Iype

2017-01-01

Background: Juvenile nasal angiofibromas (JNA) is a benign lesion with high vascularity and propensity of bone erosion leading to skull base invasion and intracranial extension. It is known to involve multiple compartments, which are often surgically difficult to access. With evolution in surgical expertise and technical innovations, endoscopic and endoscopic-assisted management has become the preferred choice of surgical management. Over the last four decades, various staging systems have been proposed, which are largely based on the extent of nasal angiofibroma. However, no clear guidelines exist for the stage-appropriate surgical management. In this study, we aim to formulate a novel staging system based on the analysis of high quality preoperative imaging and propose detailed surgical guidelines related to disease stages as observed in 242 primary cases of JNA. Methods: A retrospective analysis of the case records of 242 primary JNA cases was performed at our center. Patients were staged according to various existing staging systems as well as our own new staging system, and outcome variables were compared with respect to intraoperative blood loss, multiple staged operations, and tumor recurrences. Operative records were studied and precise endoscopic surgical guidelines were formulated for each stage. Results: Comparing the intraoperative blood loss seen in stages of various classifications, it was found that intraoperative blood loss correlated best and statistically significantly with stages in the newly proposed Janakiram staging system when compared to the existing staging systems. Staged operations were performed in a total of 7/242 patients, and there was a significant association between the requirement of a staged operation and tumor extent (Fischer's exact test, P < 0.001). Tumor recurrence was seen in 22 cases and the pterygoid wedge was found to be the most frequent site of recurrence initially. As the extent of resection improved with better surgical technique over time, recurrences were only found in superior orbital fissure, around the internal carotid artery, and in the middle cranial fossa. Conclusion: This new Janakiram staging system is based on preoperative imaging data from one of the largest JNA case series reported thus far. Respective guidelines reliably stratify patients into treatment groups with definite surgical approaches and predicts outcome. Improved surgical approaches in the modern endoscopic era have redefined JNA management with improved outcome. This study shows the importance of precise presurgical imaging and the choice of the most suitable surgical approach in reducing morbidity and mortality in JNA surgery. PMID:28540121

SOLVENT EXTRACTION PROCESS FOR THE SEPARATION OF URANIUM AND THORIUM FROM PROTACTINIUM AND FISSION PRODUCTS

DOEpatents

Rainey, R.H.; Moore, J.G.

1962-08-14

A liquid-liquid extraction process was developed for recovering thorium and uranium values from a neutron irradiated thorium composition. They are separated from a solvent extraction system comprising a first end extraction stage for introducing an aqueous feed containing thorium and uranium into the system consisting of a plurality of intermediate extractiorr stages and a second end extractron stage for introducing an aqueous immiscible selective organic solvent for thorium and uranium in countercurrent contact therein with the aqueous feed. A nitrate iondeficient aqueous feed solution containing thorium and uranium was introduced into the first end extraction stage in countercurrent contact with the organic solvent entering the system from the second end extraction stage while intro ducing an aqueous solution of salting nitric acid into any one of the intermediate extraction stages of the system. The resultant thorium and uranium-laden organic solvent was removed at a point preceding the first end extraction stage of the system. (AEC)

Validation of the Hong Kong Liver Cancer Staging System in Determining Prognosis of the North American Patients Following Intra-arterial Therapy

PubMed Central

Sohn, Jae Ho; Duran, Rafael; Zhao, Yan; Fleckenstein, Florian; Chapiro, Julius; Sahu, Sonia P.; Schernthaner, Rüdiger E.; Qian, Tianchen; Lee, Howard; Zhao, Li; Hamilton, James; Frangakis, Constantine; Lin, MingDe; Salem, Riad; Geschwind, Jean-Francois

2018-01-01

Background & Aims There is debate over the best way to stage hepatocellular carcinoma (HCC). We attempted to validate the prognostic and clinical utility of the recently developed Hong Kong Liver Cancer (HKLC) staging system, a hepatitis B-based model, and compared data with that from the Barcelona Clinic Liver Cancer (BCLC) staging system in a North American population who underwent intra-arterial therapy (IAT). Methods We performed a retrospective analysis of data from 1009 patients with HCC who underwent intra-arterial therapy from 2000 through 2014. Most patients had hepatitis C or unresectable tumors; all patients underwent IAT, with or without resection, transplantation, and/or systemic chemotherapy. We calculated HCC stage for each patient using 5-stage HKLC (HKLC-5) and 9-stage HKLC (HKLC-9) system classifications, as well as the BCLC system. Survival information was collected up until end of 2014 at which point living or unconfirmed patients were censored. We compared performance of the BCLC, HKLC-5, and HKLC-9 systems in predicting patient outcomes using Kaplan-Meier estimates, calibration plots, c-statistic, Akaike information criterion, and the likelihood ratio test. Results Median overall survival time, calculated from first IAT until date of death or censorship, for the entire cohort (all stages) was 9.8 months. The BCLC and HKLC staging systems predicted patient survival times with significance (P<.001). HKLC-5 and HKLC-9 each demonstrated good calibration. The HKLC-5 system outperformed the BCLC system in predicting patient survival times (HKLC c=0.71, Akaike information criterion=6242; BCLC c=0.64, Akaike information criterion=6320), reducing error in predicting survival time (HKLC reduced error by 14%, BCLC reduced error by 12%), and homogeneity (HKLC χ2=201; P<.001; BCLC χ2=119; P<.001) and monotonicity (HKLC linear trend χ2=193; P<.001; BCLC linear trend χ2=111; P<.001). Small proportions of patients with HCC of stages IV or V, according to the HKLC system, survived for 6 months and 4 months, respectively. Conclusion In a retrospective analysis of patients who underwent IAT for unresectable HCC, we found the HKLC-5 staging system to have the best combination of performances in survival separation, calibration, and discrimination; it consistently outperformed the BCLC system in predicting survival times of patients. The HKLC system identified patients with HCC of stages IV and V who are unlikely to benefit from IAT. PMID:27847278

Validation of the Hong Kong Liver Cancer Staging System in Determining Prognosis of the North American Patients Following Intra-arterial Therapy.

PubMed

Sohn, Jae Ho; Duran, Rafael; Zhao, Yan; Fleckenstein, Florian; Chapiro, Julius; Sahu, Sonia; Schernthaner, Rüdiger E; Qian, Tianchen; Lee, Howard; Zhao, Li; Hamilton, James; Frangakis, Constantine; Lin, MingDe; Salem, Riad; Geschwind, Jean-Francois

2017-05-01

There is debate over the best way to stage hepatocellular carcinoma (HCC). We attempted to validate the prognostic and clinical utility of the recently developed Hong Kong Liver Cancer (HKLC) staging system, a hepatitis B-based model, and compared data with that from the Barcelona Clinic Liver Cancer (BCLC) staging system in a North American population that underwent intra-arterial therapy (IAT). We performed a retrospective analysis of data from 1009 patients with HCC who underwent IAT from 2000 through 2014. Most patients had hepatitis C or unresectable tumors; all patients underwent IAT, with or without resection, transplantation, and/or systemic chemotherapy. We calculated HCC stage for each patient using 5-stage HKLC (HKLC-5) and 9-stage HKLC (HKLC-9) system classifications, and the BCLC system. Survival information was collected up until the end of 2014 at which point living or unconfirmed patients were censored. We compared performance of the BCLC, HKLC-5, and HKLC-9 systems in predicting patient outcomes using Kaplan-Meier estimates, calibration plots, C statistic, Akaike information criterion, and the likelihood ratio test. Median overall survival time, calculated from first IAT until date of death or censorship, for the entire cohort (all stages) was 9.8 months. The BCLC and HKLC staging systems predicted patient survival times with significance (P < .001). HKLC-5 and HKLC-9 each demonstrated good calibration. The HKLC-5 system outperformed the BCLC system in predicting patient survival times (HKLC C = 0.71, Akaike information criterion = 6242; BCLC C = 0.64, Akaike information criterion = 6320), reducing error in predicting survival time (HKLC reduced error by 14%, BCLC reduced error by 12%), and homogeneity (HKLC chi-square = 201, P < .001; BCLC chi-square = 119, P < .001) and monotonicity (HKLC linear trend chi-square = 193, P < .001; BCLC linear trend chi-square = 111, P < .001). Small proportions of patients with HCC of stages IV or V, according to the HKLC system, survived for 6 months and 4 months, respectively. In a retrospective analysis of patients who underwent IAT for unresectable HCC, we found the HKLC-5 staging system to have the best combination of performances in survival separation, calibration, and discrimination; it consistently outperformed the BCLC system in predicting survival times of patients. The HKLC system identified patients with HCC of stages IV and V who are unlikely to benefit from IAT. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Two-statge sorption type cryogenic refrigerator including heat regeneration system

NASA Technical Reports Server (NTRS)

Jones, Jack A. (Inventor); Wen, Liang-Chi (Inventor); Bard, Steven (Inventor)

1989-01-01

A lower stage chemisorption refrigeration system physically and functionally coupled to an upper stage physical adsorption refrigeration system. Waste heat generated by the lower stage cycle is regenerated to fuel the upper stage cycle thereby greatly improving the energy efficiency of a two-stage sorption refrigerator. The two stages are joined by disposing a first pressurization chamber providing a high pressure flow of a first refrigerant for the lower stage refrigeration cycle within a second pressurization chamber providing a high pressure flow of a second refrigerant for the upper stage refrigeration cycle. The first pressurization chamber is separated from the second pressurization chamber by a gas-gap thermal switch which at times is filled with a thermoconductive fluid to allow conduction of heat from the first pressurization chamber to the second pressurization chamber.

Apical extrusion of debris during the preparation of oval root canals: a comparative study between a full-sequence SAF system and a rotary file system supplemented by XP-endo finisher file.

PubMed

Kfir, Anda; Moza-Levi, Rotem; Herteanu, Moran; Weissman, Amir; Wigler, Ronald

2018-03-01

The purpose of this study was to assess the amount of apically extruded debris during the preparation of oval canals with either a rotary file system supplemented by the XP-endo Finisher file or a full-sequence self-adjusting file (SAF) system. Sixty mandibular incisors were randomly assigned to two groups: group A: stage 1-glide path preparation with Pre-SAF instruments. Stage 2-cleaning and shaping with SAF. Group B: stage 1-glide path preparation with ProGlider file. Stage 2-cleaning and shaping with ProTaper Next system. Stage 3-Final cleaning with XP-endo Finisher file. The debris extruded during each of the stages was collected, and the debris weights were compared between the groups and between the stages within the groups using t tests with a significance level set at P < 0.05. The complete procedure for group B resulted in significantly more extruded debris compared to group A. There was no significant difference between the stages in group A, while there was a significant difference between stage 2 and stages 1 and 3 in group B, but no significant difference between stages 1 and 3. Both instrumentation protocols resulted in extruded debris. Rotary file followed by XP-endo Finisher file extruded significantly more debris than a full-sequence SAF system. Each stage, in either procedure, had its own contribution to the extrusion of debris. Final preparation with XP-endo Finisher file contributes to the total amount of extruded debris, but the clinical relevance of the relative difference in the amount of apically extruded debris remains unclear.

Thiol-vinyl systems as shape memory polymers and novel two-stage reactive polymer systems

NASA Astrophysics Data System (ADS)

Nair, Devatha P.

2011-12-01

The focus of this research was to formulate, characterize and tailor the reaction methodologies and material properties of thiol-vinyl systems to develop novel polymer platforms for a range of engineering applications. Thiol-ene photopolymers were demonstrated to exhibit several advantageous characteristics for shape memory polymer systems for a range of biomedical applications. The thiol-ene shape memory polymer systems were tough and flexible as compared to the acrylic control systems with glass transition temperatures between 30 and 40 °C; ideal for actuation at body temperature. The thiol-ene polymers also exhibited excellent shape fixity and a rapid and distinct shape memory actuation response along with free strain recoveries of greater than 96% and constrained stress recoveries of 100%. Additionally, two-stage reactive thiol-acrylate systems were engineered as a polymer platform technology enabling two independent sets of polymer processing and material properties. There are distinct advantages to designing polymer systems that afford two distinct sets of material properties -- an intermediate polymer that would enable optimum handling and processing of the material (stage 1), while maintaining the ability to tune in different, final properties that enable the optimal functioning of the polymeric material (stage 2). To demonstrate the range of applicability of the two-stage reactive systems, three specific applications were demonstrated; shape memory polymers, lithographic impression materials, and optical materials. The thiol-acrylate reactions exhibit a wide range of application versatility due to the range of available thiol and acrylate monomers as well as reaction mechanisms such as Michael Addition reactions and free radical polymerizations. By designing a series of non-stoichiometeric thiol-acrylate systems, a polymer network is initially formed via a base catalyzed 'click' Michael addition reaction. This self-limiting reaction results in a Stage 1 polymer with excess acrylic functional groups within the network. At a later point in time, the photoinitiated, free radical polymerization of the excess acrylic functional groups results in a highly crosslinked, robust material system. By varying the monomers within the system as well as the stoichiometery of thiol to acrylate functional groups, the ability of the two-stage reactive systems to encompass a wide range of properties at the end of both the stage 1 and stage 2 polymerizations was demonstrated. The thiol-acrylate networks exhibited intermediate Stage 1 rubbery moduli and glass transition temperatures that range from 0.5 MPa and -10 ºC to 22 MPa and 22 ºC respectively. The same polymer networks can then attain glass transition temperatures that range from 5 ºC to 195 ºC and rubbery moduli of up to 200 MPa after the subsequent photocure stage. Two-stage reactive polymer composite systems were also formulated and characterized for thermomechanical and mechanical properties. Thermomechanical analysis showed that the fillers resulted in a significant increase in the modulus at both stage 1 and stage 2 polymerizations without a significant change in the glass transition temperatures (Tg). The two-stage reactive matrix composite formed with a hexafunctional acrylate matrix and 20 volume % silica particles showed a 125% increase in stage 1 modulus and 101% increase in stage 2 modulus, when compared with the modulus of the neat matrix. Finally, the two-stage reactive polymeric devices were formulated and designed as orthopedic suture anchors for arthroscopic surgeries and mechanically characterized. The Stage 1 device was designed to exhibit properties ideal for arthroscopic delivery and device placement with glass transition temperatures 25 -- 30 °C and rubbery moduli ˜ 95 MPa. The subsequent photopolymerization generated Stage 2 polymers designed to match the local bone environment with moduli ranging up to 2 GPa. Additionally, pull-out strengths of 140 N were demonstrated and are equivalent to the pull-strengths achieved by other commercially available suture anchors.

Stage III nasopharyngeal angiofibroma: Improving results with endoscopic-assisted midfacial degloving and modification to the Fisch staging system.

PubMed

Shah, Saurin R; Keshri, Amit; Patadia, Simple; Sahu, Rabi Narayan; Srivastava, Arun Kumar; Behari, Sanjay

2015-10-01

To study outcomes with endoscopic-assisted midfacial degloving for Fisch stage III nasopharyngeal angiofibroma and propose a new staging system. Retrospective study of patients with Fisch stage III juvenile nasopharyngeal angiofibroma (JNA) including preoperative angiography, intraoperative blood loss and residue/recurrence following surgery. Tertiary care superspecialty referral center. Fifteen consecutive patients with Fisch stage III JNA undergoing operations over a period of 18 months. Preoperative angiography details, intraoperative blood loss, residue/recurrence, complications of surgery. Transarterial embolization with particulate agents followed by endoscopic-assisted midfacial degloving provides excellent outcomes with Fisch stage III JNAs. The modified Fisch staging system proposed would allow better preoperative evaluation and comparison of outcomes with different treatment options for stage III JNAs. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Effectiveness of cervical screening after age 60 years according to screening history: Nationwide cohort study in Sweden.

PubMed

Wang, Jiangrong; Andrae, Bengt; Sundström, Karin; Ploner, Alexander; Ström, Peter; Elfström, K Miriam; Dillner, Joakim; Sparén, Pär

2017-10-01

The relatively high incidence of cervical cancer in women at older ages is a continuing concern in countries with long-established cervical screening. Controversy remains on when and how to cease screening. Existing population-based studies on the effectiveness of cervical screening at older ages have not considered women's screening history. We performed a nationwide cohort study to investigate the incidence of cervical cancer after age 60 years and its association with cervical screening at age 61-65, stratified by screening history at age 51-60. Using the Total Population Register, we identified 569,132 women born between 1 January 1919 and 31 December 1945, resident in Sweden since age 51. Women's cytological screening records, cervical cancer occurrence, and FIGO stage (for those diagnosed with cancer) were retrieved from national registers and medical charts. We calculated the cumulative incidence of cervical cancer from age 61 to age 80 using a survival function considering competing risk, and estimated the hazard ratio (HR) of cervical cancer in relation to screening status at age 61-65 from Cox models, adjusted for birth cohort and level of education, conditioning on women's screening history in their 50s. In women unscreened in their 50s, the cumulative incidence up to age 80 was 5.0 per 1,000 women, and screening at age 61-65 was associated with a lower risk for cervical cancer (HR = 0.42, 95% CI 0.24-0.72), corresponding to a decrease of 3.3 cancer cases per 1,000 women. A higher cumulative incidence and similarly statistically significant risk decrease was seen for women with abnormal smears in their 50s. In women adequately or inadequately screened with only normal results between age 51 and age 60, the cumulative incidence of cervical cancer from age 61 to 80 was 1.6 and 2.5 per 1,000 women, respectively, and further screening at age 61-65 was not associated with statistically significant decreases of cervical cancer risk up to age 80, but with fewer cancer cases of advanced stages at age 61-65. Adjustment for potential lifestyle confounders was limited. In this study, cervical screening with cytology at age 61-65 was associated with a statistically significant reduction of subsequent cervical cancer risk for women who were unscreened, or screened with abnormalities, in their 50s. In women screened with normal results in their 50s, the risk for future cancer was not sizeable, and the risk reduction associated with continued screening appeared limited. These findings should inform the current debate regarding age and criteria to discontinue cervical screening.

Reduced Boil-Off System Sizing

NASA Technical Reports Server (NTRS)

Guzik, Monica C.; Plachta, David W.; Feller, Jeffrey R.

2015-01-01

NASA is currently developing cryogenic propellant storage and transfer systems for future space exploration and scientific discovery missions by addressing the need to raise the technology readiness level of cryogenic fluid management technologies. Cryogenic propellants are baselined in many propulsion systems due to their inherently high specific impulse; however, their low boiling points can cause substantial boil-off losses over time. Recent efforts such as the Reduced Boil-off Testing and the Active Thermal Control Scaling Study provide important information on the benefit of an active cooling system applied to LH2 propellant storage. Findings show that zero-boil off technologies can reduce overall mass in LH2 storage systems when low Earth orbit loiter periods extend beyond two months. A significant part of this mass reduction is realized by integrating two stages of cooling: a 20 K stage to intercept heat at the tank surface, and a 90 K stage to reduce the heat entering the less efficient 20 K stage. A missing element in previous studies, which is addressed in this paper, is the development of a direct method for sizing the 90 K cooling stage. Such a method requires calculation of the heat entering both the 90 K and 20 K stages as compared to the overall system masses, and is reliant upon the temperature distribution, performance, and unique design characteristics of the system in question. By utilizing the known conductance of a system without active thermal control, the heat being intercepted by a 90 K stage can be calculated to find the resultant lift and mass of each active thermal control stage. Integral to this is the thermal conductance of the cooling straps and the broad area cooling shield, key parts of the 90 K stage. Additionally, a trade study is performed to show the ability of the 90 K cooling stage to reduce the lift on the 20 K cryocooler stage, which is considerably less developed and efficient than 90 K cryocoolers.

Design and operation of an anaerobic digester for waste management and fuel generation during long term lunar mission

NASA Astrophysics Data System (ADS)

Dhoble, Abhishek S.; Pullammanappallil, Pratap C.

2014-10-01

Waste treatment and management for manned long term exploratory missions to moon will be a challenge due to longer mission duration. The present study investigated appropriate digester technologies that could be used on the base. The effect of stirring, operation temperature, organic loading rate and reactor design on the methane production rate and methane yield was studied. For the same duration of digestion, the unmixed digester produced 20-50% more methane than mixed system. Two-stage design which separated the soluble components from the solids and treated them separately had more rapid kinetics than one stage system, producing the target methane potential in one-half the retention time than the one stage system. The two stage system degraded 6% more solids than the single stage system. The two stage design formed the basis of a prototype digester sized for a four-person crew during one year exploratory lunar mission.

International neuroblastoma staging system stage 1 neuroblastoma: a prospective study and literature review.

PubMed

Kushner, B H; Cheung, N K; LaQuaglia, M P; Ambros, P F; Ambros, I M; Bonilla, M A; Ladanyi, M; Gerald, W L

1996-07-01

To gain insight into the management of non-metastatic neuroblastoma by examining clinical and biologic features of International Neuroblastoma Staging System (INSS) stage 1 tumors. Patients were staged by both the INSS and the Evans staging system and were evaluated for biologic prognostic factors. Patients with INSS stage 1 received no cytotoxic therapy. The literature was reviewed for clinical and biologic data about INSS stage 1. We evaluated 10 consecutive patients (median age, 17.5 months) with INSS stage 1; all remain disease-free (median follow-up duration, > 5 years). Tumors were in the abdomen (n = 6), chest (n = 3), or pelvis (n = 1). Neuroblastoma involved margins of resection in six tumors. Poor-prognostic biologic findings included tumor-cell diploidy (n = 2) and unfavorable Shimada histopathology (n = 2). Two patients were to receive chemotherapy for, respectively, a tumor deemed unresectable and a tumor classified as Evans stage III; second opinions resulted in surgical management alone in each case. Published reports confirm that some INSS stage 1 patients (1) are at risk for overtreatment, and (2) have poor-prognostic biologic findings yet do well. Surgery alone suffices for INSS stage 1 neuroblastoma, even if biologic prognostic factors are unfavorable, microscopic disease remains after surgery, and tumor size is suggestive of "advanced-stage" status in other staging systems. Attempts to resect regionally confined neuroblastomas should take precedence over immediate use of cytotoxic therapy; otherwise, some patients may receive chemotherapy or radiotherapy unnecessarily.

Dilemmas in Lung Cancer Staging.

PubMed

Vlahos, Ioannis

2018-05-01

The advent of the 8th edition of the lung cancer staging system reflects a further meticulous evidence-based advance in the stratification of the survival of patients with lung cancer. Although addressing many limitations of earlier staging systems, several limitations in staging remain. This article reviews from a radiological perspective the limitations of the current staging system, highlighting the process of TNM restructuring, the residual issues with regards to the assignment of T, N, M descriptors, and their associated stage groupings and how these dilemmas impact guidance of multidisciplinary teams taking care of patients with lung cancer. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Influence of dispatching rules on average production lead time for multi-stage production systems.

PubMed

Hübl, Alexander; Jodlbauer, Herbert; Altendorfer, Klaus

2013-08-01

In this paper the influence of different dispatching rules on the average production lead time is investigated. Two theorems based on covariance between processing time and production lead time are formulated and proved theoretically. Theorem 1 links the average production lead time to the "processing time weighted production lead time" for the multi-stage production systems analytically. The influence of different dispatching rules on average lead time, which is well known from simulation and empirical studies, can be proved theoretically in Theorem 2 for a single stage production system. A simulation study is conducted to gain more insight into the influence of dispatching rules on average production lead time in a multi-stage production system. We find that the "processing time weighted average production lead time" for a multi-stage production system is not invariant of the applied dispatching rule and can be used as a dispatching rule independent indicator for single-stage production systems.

A novel acute HIV infection staging system based on 4th generation immunoassay.

PubMed

Ananworanich, Jintanat; Fletcher, James L K; Pinyakorn, Suteeraporn; van Griensven, Frits; Vandergeeten, Claire; Schuetz, Alexandra; Pankam, Tippawan; Trichavaroj, Rapee; Akapirat, Siriwat; Chomchey, Nitiya; Phanuphak, Praphan; Chomont, Nicolas; Michael, Nelson L; Kim, Jerome H; de Souza, Mark

2013-05-29

Fourth generation (4thG) immunoassay (IA) is becoming the standard HIV screening method but was not available when the Fiebig acute HIV infection (AHI) staging system was proposed. Here we evaluated AHI staging based on a 4thG IA (4thG staging). Screening for AHI was performed in real-time by pooled nucleic acid testing (NAT, n=48,828 samples) and sequential enzyme immunoassay (EIA, n=3,939 samples) identifying 63 subjects with non-reactive 2nd generation EIA (Fiebig stages I (n=25), II (n=7), III (n=29), IV (n=2)). The majority of samples tested (n=53) were subtype CRF_01AE (77%). NAT+ subjects were re-staged into three 4thG stages: stage 1 (n=20; 4th gen EIA-, 3rd gen EIA-), stage 2 (n=12; 4th gen EIA+, 3rd gen EIA-), stage 3 (n=31; 4th gen EIA+, 3rd gen EIA+, Western blot-/indeterminate). 4thG staging distinguishes groups of AHI subjects by time since presumed HIV exposure, pattern of CD8+ T, B and natural killer cell absolute numbers, and HIV RNA and DNA levels. This staging system further stratified Fiebig I subjects: 18 subjects in 4thG stage 1 had lower HIV RNA and DNA levels than 7 subjects in 4thG stage 2. Using 4th generation IA as part of AHI staging distinguishes groups of patients by time since exposure to HIV, lymphocyte numbers and HIV viral burden. It identifies two groups of Fiebig stage I subjects who display different levels of HIV RNA and DNA, which may have implication for HIV cure. 4th generation IA should be incorporated into AHI staging systems.

Symbolic rule-based classification of lung cancer stages from free-text pathology reports.

PubMed

Nguyen, Anthony N; Lawley, Michael J; Hansen, David P; Bowman, Rayleen V; Clarke, Belinda E; Duhig, Edwina E; Colquist, Shoni

2010-01-01

To classify automatically lung tumor-node-metastases (TNM) cancer stages from free-text pathology reports using symbolic rule-based classification. By exploiting report substructure and the symbolic manipulation of systematized nomenclature of medicine-clinical terms (SNOMED CT) concepts in reports, statements in free text can be evaluated for relevance against factors relating to the staging guidelines. Post-coordinated SNOMED CT expressions based on templates were defined and populated by concepts in reports, and tested for subsumption by staging factors. The subsumption results were used to build logic according to the staging guidelines to calculate the TNM stage. The accuracy measure and confusion matrices were used to evaluate the TNM stages classified by the symbolic rule-based system. The system was evaluated against a database of multidisciplinary team staging decisions and a machine learning-based text classification system using support vector machines. Overall accuracy on a corpus of pathology reports for 718 lung cancer patients against a database of pathological TNM staging decisions were 72%, 78%, and 94% for T, N, and M staging, respectively. The system's performance was also comparable to support vector machine classification approaches. A system to classify lung TNM stages from free-text pathology reports was developed, and it was verified that the symbolic rule-based approach using SNOMED CT can be used for the extraction of key lung cancer characteristics from free-text reports. Future work will investigate the applicability of using the proposed methodology for extracting other cancer characteristics and types.

Cervical poorly differentiated adenocarcinoma with dominant choriocarcinomatous pattern--A case report.

PubMed

Nikolić, Branka; Ćurković, Aleksandar; Dikić, Svetlana Dragojević; Mitrović, Ana; Kuzmanović, Igor; Arandjelović, Aleksandra; Stanković, Goran

2015-07-01

Gestational trophoblastic neoplasm (GTN), choriocarcinoma in coexistence with primary cervical adenocarcinoma, is a rare event not easy to diagnose. Choriocarcinoma is a malignant form of GTN but curable if metastases do not appear early and spread fast. We presented choriocarcinoma in coexistence with primary cervical adenocarcinoma in a 48-year-old patient who had radical hysterectomy because of confirmed cervical carcinoma (Dg: Carcinomaporo vaginalis uteri FIGO st I B1). Histological findings confirmed cervical choriocarcinoma with extensive vascular invasion and apoptosis but GTN choriocarcinoma was finally confirmed after immunohystochemical examinations. Preoperative serum human gonadotropine (beta hCG) level stayed unknown. This patient did not have any pregnancy-like symptoms before the operation. The first beta hCG monitoring was done two months after the operation and found negative. According to the final diagnosis the decision of Consilium for Malignant Diseases was that this patient needed serum hCG monitoring as well as treatment with chemotherapy for high-risk GTN and consequent irradiation for adenocarcinoma. The early and proper diagnosis of nonmetastatic choriocarcinoma of nongestational origine in coexistence with cervical carcinoma is curable and can have good prognosis.

Modifying the criteria of the American Joint Commission on Cancer staging system in melanoma.

PubMed

Ross, M

1998-03-01

The currently used staging system in melanoma has not been significantly modified since 1988. While this four-stage system effectively stratifies patients into prognostic groups, additional discriminating criteria have been reported that is not presently incorporated in the staging system. The following additions and modifications are suggested based on a review of the recent literature: 1) for stage I and II patients, Clark's level of invasion is only predictive in patients with melanomas less than 1 mm, the best statistical fit for tumor thickness cutoffs are less than 1 mm, 1 to 2 mm, 2 to 4 mm, and greater than 4 mm, and ulceration should be included as part of the staging system; 2) in stage III patients, the presently used criteria of 3 cm in size needs to abandoned and replaced by the number of lymph nodes involved and the number of lymph node basins involved; and 3) local recurrence presenting as local metastases and satellite disease represent a biologic continuum of regional lymphatic dissemination and should both be classified in the stage III prognostic groups. These modifications, if accepted, should provide the ability to better stratify patients for future adjuvant therapy trials.

Pre-defined and optional staging for the deployment of enterprise systems: a case study and a framework

NASA Astrophysics Data System (ADS)

Lichtenstein, Yossi; Cucuy, Shy; Fink, Lior

2017-03-01

The effective deployment of enterprise systems has been a major challenge for many organisations. Customising the new system, changing business processes, and integrating multiple information sources are all difficult tasks. As such, they are typically done in carefully planned stages in a process known as phased implementation. Using ideas from Option Theory, this article critiques aspects of phased implementation. One customer relationship management (CRM) project and its phased implementation are described in detail and ten other enterprise system deployments are summarised as a basis for the observation that almost all deployment stages are pre-defined operational steps rather than decision points. However, Option Theory suggests that optional stages, to be used only when risk materialises, should be integral parts of project plans. Although such optional stages are often more valuable than pre-defined stages, the evidence presented in this article shows that they are only rarely utilised. Therefore, a simple framework is presented; it first identifies risks related to the deployment of enterprise systems, then identifies optional stages that can mitigate these risks, and finally compares the costs and benefits of both pre-defined and optional stages.

Results of a multicenter survey showing interindividual variability among neurosurgeons when deciding on the radicality of surgical resection in glioblastoma highlight the need for more objective guidelines.

PubMed

Capellades, J; Teixidor, P; Villalba, G; Hostalot, C; Plans, G; Armengol, R; Medrano, S; Estival, A; Luque, R; Gonzalez, S; Gil-Gil, M; Villa, S; Sepulveda, J; García-Mosquera, J J; Balana, C

2017-06-01

We assessed agreement among neurosurgeons on surgical approaches to individual glioblastoma patients and between their approach and those recommended by the topographical staging system described by Shinoda. Five neurosurgeons were provided with pre-surgical MRIs of 76 patients. They selected the surgical approach [biopsy, partial resection, or gross total resection (GTR)] that they would recommend for each patient. They were blinded to each other's response and they were told that patients were younger than 50 years old and without symptoms. Three neuroradiologists classified each case according to the Shinoda staging system. Biopsy was recommended in 35.5-82.9%, partial resection in 6.6-32.9%, and GTR in 3.9-31.6% of cases. Agreement among their responses was fair (global kappa = 0.28). Nineteen patients were classified as stage I, 14 as stage II, and 43 as stage III. Agreement between the neurosurgeons and the recommendations of the staging system was poor for stage I (kappa = 0.14) and stage II (kappa = 0.02) and fair for stage III patients (kappa = 0.29). An individual analysis revealed that in contrast to the Shinoda system, neurosurgeons took into account T2/FLAIR sequences and gave greater weight to the involvement of eloquent areas. The surgical approach to glioblastoma is highly variable. A staging system could be used to examine the impact of extent of resection, monitor post-operative complications, and stratify patients in clinical trials. Our findings suggest that the Shinoda staging system could be improved by including T2/FLAIR sequences and a more adequate weighting of eloquent areas.

Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis

PubMed Central

McLeod, Donald S.A.; Jonklaas, Jacqueline; Brierley, James D.; Ain, Kenneth B.; Cooper, David S.; Fein, Henry G.; Haugen, Bryan R.; Ladenson, Paul W.; Magner, James; Ross, Douglas S.; Skarulis, Monica C.; Steward, David L.; Xing, Mingzhao; Litofsky, Danielle R.; Maxon, Harry R.

2015-01-01

Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned. Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer. Methods: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R2). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination. Results: The best five alternate papillary cancer systems had age cut-points of 45–50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p = 0.200). The best five alternate follicular cancer systems had age cut-points of 50–55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p = 0.003–0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p = 0.197). Conclusions: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation. PMID:26203804

Inter-stage thermophilic aerobic digestion may increase organic matter removal from wastewater sludge without decreasing biogas production.

PubMed

Hafner, Sasha D; Madsen, Johan T; Pedersen, Johanna M; Rennuit, Charlotte

2018-02-01

Combining aerobic and anaerobic digestion in a two-stage system can improve the degradation of wastewater sludge over the use of either technology alone. But use of aerobic digestion as a pre-treatment before anaerobic digestion generally reduces methane production due to loss of substrate through oxidation. An inter-stage configuration may avoid this reduction in methane production. Here, we evaluated the use of thermophilic aerobic digestion (TAD) as an inter-stage treatment for wastewater sludge using laboratory-scale semi-continuous reactors. A single anaerobic digester was compared to an inter-stage system, where a thermophilic aerobic digester (55 °C) was used between two mesophilic anaerobic digesters (37 °C). Both systems had retention times of approximately 30 days, and the comparison was based on measurements made over 97 days. Results showed that the inter-stage system provided better sludge destruction (52% volatile solids (VS) removal vs. 40% for the single-stage system, 44% chemical oxygen demand (COD) removal vs. 34%) without a decrease in total biogas production (methane yield per g VS added was 0.22-0.24 L g -1 for both systems).

Expendable second stage reusable space shuttle booster. Volume 2: Technical summary. Book 3: Booster vehicle modifications and ground systems definition

NASA Technical Reports Server (NTRS)

1972-01-01

A definition of the expendable second stage and space shuttle booster separation system is presented. Modifications required on the reusable booster for expendable second stage/payload flight and the ground systems needed to operate the expendable second stage in conjuction with the space shuttle booster are described. The safety, reliability, and quality assurance program is explained. Launch complex operations and services are analyzed.

Study of Alternate Space Shuttle Concepts. Volume 2. Part 1: Concept Analysis and Definition

NASA Technical Reports Server (NTRS)

1971-01-01

Three different space shuttle systems have been defined and analyzed. The first is a stage-and-one-half system optimized to meet program requirements. The second is a two-stage, fully reusable system also designed to meet program requirements. The third is a convertible system which operates initially as a stage-and-one-half system and is subsequently converted to a two-stage, fully reusable system by reconfiguration of the orbiter vehicle and development of a booster vehicle. The design and performance of this third system must necessarily be compromised somewhat to facilitate the conversion. For each system, the applicable requirements, ground rules, and assumptions are defined. The characteristics of each system are listed and a detailed description and analysis of the system are presented. Finally, a cost analysis for the system is given.

A discussion of serum albumin level in advanced-stage hepatocellular carcinoma: a medical oncologist's perspective.

PubMed

Tanriverdi, Ozgur

2014-11-01

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and it is particularly prevalent in East and Southeast Asia. With surgical and/or local interventional treatment methods, survival rates for early-stage hepatocellular cancers have increased. However, it is not yet clear which staging systems are more applicable in hepatocellular carcinoma. Serum albumin level is already being used as a criterion in most staging systems. Albumin is an important serum protein in human bodily functions, but only 5 % of the daily amount needed is synthesized by the liver. The serum albumin level is affected by multifactorial situations, including capillary permeability, drugs, liver insufficiency, inflammation and/or infections, dehydration or overhydration, protein loosing disorders, and decreased nutrition intake in anorexia-malnutrition syndrome and cancer cachexia. Because of this complex situation, serum albumin level may affect many staging systems for hepatocellular carcinoma by leading to false-negative results. In this paper, the statuses of current staging systems are reviewed, and possible negative events regarding the serum albumin levels found in these staging systems are discussed.

[Utilize the simplified POP-Q system in the clinical practice of staging for pelvic organ prolapse: comparative analysis with standard POP-Q system].

PubMed

Zhang, H; Zhu, L; Xu, T; Lang, J H

2016-07-25

To determine the association between simplified pelvic organ prolapse quantification system(S-POP-Q)and the standard pelvic organ prolapse quantification system(POP-Q)in describing pelvic organ prolapse. This was an observational study. From Jan. 2010 to Jan. 2014, 256 subjects with pelvic floor disorder symptoms underwent two exams: a POP-Q exam and a S-POP-Q exam. For the S-POP-Q system, vaginal segments of the exam were defined using points Ba, Bp, C, and D. For the POP-Q system vaginal segments of the exam were defined using points Aa, Ba, Ap, Bp, C, and D. The inter-system consistency between the overall ordinal stages, the anterior vaginal wall stages, the posterior vaginal wall stages, the cervix stages, the posterior fornix or vaginal cuff stages from each two kind of exam were compared. The Kendall tau-b correlation coefficient for overall stage was 0.81, the Kendall tau-b correlation coefficients were 0.81, 0.81, 0.85, 0.88 for the anterior vaginal wall, for the posterior vaginal wall, for the cervix, for the posterior fornix or vaginal cuff, respectively. There is almost perfect association between S-POP-Q and POP-Q in describing pelvic organ prolapse.

76 FR 40497 - Medicare Program; Changes to the End-Stage Renal Disease Prospective Payment System for CY 2012...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

...] RIN 0938-AQ27 Medicare Program; Changes to the End-Stage Renal Disease Prospective Payment System for... through Federal Digital System (FDsys), a service of the U.S. Government Printing Office. This database... Internet on the CMS Web site. The Addenda to the End-Stage Renal Disease (ESRD) Prospective Payment System...

The 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system for gastric cancer is superior to the 7th edition: results from a Chinese mono-institutional study of 1663 patients.

PubMed

Ji, Xin; Bu, Zhao-De; Yan, Yan; Li, Zi-Yu; Wu, Ai-Wen; Zhang, Lian-Hai; Zhang, Ji; Wu, Xiao-Jiang; Zong, Xiang-Long; Li, Shuang-Xi; Shan, Fei; Jia, Zi-Yu; Ji, Jia-Fu

2017-11-22

We investigated the superiority of the 8th edition of the tumor-node-metastasis (TNM) system for patients in China with gastric cancer. The survival outcomes of 1663 patients with gastric cancer undergoing radical resection were analyzed. In the 8th edition system, homogeneous 5-year survival rates among different pathological TNM (pTNM) categories belonging to the same stage were observed. However, in the 7th edition system, the differences of 5-year survival rate among pTNM categories belonging to the same stage were observed in stages IIB (P = 0.010), IIIB (P = 0.004), and IIIC (P < 0.001). For patients in the pT1-3 (P < 0.001) and pT4a (P < 0.001) categories, there were significant differences in survival between patients in the pN3a and pN3b categories. Furthermore, partial cases (pT4bN0M0/T4aN2M0) of stage IIIB were downstaged to stage IIIA in the 8th edition system, and the 5-year survival rate of these patients was significantly better than that of patients in stage IIIB in the 8th edition system. Similarly, the 5-year survival rate of patients in p4bN2M0/T4aN3aM0 downstaged from stage IIIC to IIIB was significantly better than that of patients in stage IIIC. Compared with the 7th edition system, the 8th edition system had a higher likelihood ratio and linear trend chi-squared score and a smaller Akaike information criteria value. The 8th edition system is superior to the 7th edition system in terms of homogeneity, discriminatory ability, and monotonicity of gradients for Chinese patients with gastric cancer.

Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer.

PubMed

Jaaback, Kenneth; Johnson, Nick; Lawrie, Theresa A

2011-11-09

Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy. To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer. We searched the Gynaecological Cancer Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010 and May 2011. In addition, we handsearched and cascade searched the major gynaecological oncology journals. The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration. We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software. Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0.81; 95% confidence interval (CI): 0.72 to 0.90). Intraperitoneal component chemotherapy prolonged the disease-free interval (five studies, 1311 women; HR = 0.78; 95% CI: 0.70 to 0.86). There was greater serious toxicity with regard to gastrointestinal effects, pain, fever and infection but less ototoxicity with the IP than the IV route. Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials.

In Vivo and In Vitro Characterization of a Plasmodium Liver Stage-Specific Promoter

PubMed Central

Horstmann, Sebastian; Annoura, Takeshi; del Portillo, Hernando A.; Khan, Shahid M.; Heussler, Volker T.

2015-01-01

Little is known about stage-specific gene regulation in Plasmodium parasites, in particular the liver stage of development. We have previously described in the Plasmodium berghei rodent model, a liver stage-specific (lisp2) gene promoter region, in vitro. Using a dual luminescence system, we now confirm the stage specificity of this promoter region also in vivo. Furthermore, by substitution and deletion analyses we have extended our in vitro characterization of important elements within the promoter region. Importantly, the dual luminescence system allows analyzing promoter constructs avoiding mouse-consuming cloning procedures of transgenic parasites. This makes extensive mutation and deletion studies a reasonable approach also in the malaria mouse model. Stage-specific expression constructs and parasite lines are extremely valuable tools for research on Plasmodium liver stage biology. Such reporter lines offer a promising opportunity for assessment of liver stage drugs, characterization of genetically attenuated parasites and liver stage-specific vaccines both in vivo and in vitro, and may be key for the generation of inducible systems. PMID:25874388

Effect of ammoniacal nitrogen on one-stage and two-stage anaerobic digestion of food waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ariunbaatar, Javkhlan, E-mail: jaka@unicas.it; UNESCO-IHE Institute for Water Education, Westvest 7, 2611 AX Delft; Scotto Di Perta, Ester

Highlights: • Almost 100% of the biomethane potential of food waste was recovered during AD in a two-stage CSTR. • Recirculation of the liquid fraction of the digestate provided the necessary buffer in the AD reactors. • A higher OLR (0.9 gVS/L·d) led to higher accumulation of TAN, which caused more toxicity. • A two-stage reactor is more sensitive to elevated concentrations of ammonia. • The IC{sub 50} of TAN for the AD of food waste amounts to 3.8 g/L. - Abstract: This research compares the operation of one-stage and two-stage anaerobic continuously stirred tank reactor (CSTR) systems fed semi-continuouslymore » with food waste. The main purpose was to investigate the effects of ammoniacal nitrogen on the anaerobic digestion process. The two-stage system gave more reliable operation compared to one-stage due to: (i) a better pH self-adjusting capacity; (ii) a higher resistance to organic loading shocks; and (iii) a higher conversion rate of organic substrate to biomethane. Also a small amount of biohydrogen was detected from the first stage of the two-stage reactor making this system attractive for biohythane production. As the digestate contains ammoniacal nitrogen, re-circulating it provided the necessary alkalinity in the systems, thus preventing an eventual failure by volatile fatty acids (VFA) accumulation. However, re-circulation also resulted in an ammonium accumulation, yielding a lower biomethane production. Based on the batch experimental results the 50% inhibitory concentration of total ammoniacal nitrogen on the methanogenic activities was calculated as 3.8 g/L, corresponding to 146 mg/L free ammonia for the inoculum used for this research. The two-stage system was affected by the inhibition more than the one-stage system, as it requires less alkalinity and the physically separated methanogens are more sensitive to inhibitory factors, such as ammonium and propionic acid.« less

The tumor-stromal ratio as a strong prognosticator for advanced gastric cancer patients: proposal of a new TSNM staging system.

PubMed

Peng, Chunwei; Liu, Jiuyang; Yang, Guifang; Li, Yan

2018-05-01

Insufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance. Tissue samples from the most invasive part of the primary gastric cancer (GC) of 494 patients were analyzed for their TSR, and a new TSNM (tumor-stromal node metastasis) staging system based on patho-biological behaviors was established and assessed. TSR is a new and strong independent prognostic factor for GC patients. The likelihood of tumor invasion is increased significantly for patients in the stromal-high subgroup compared to those in the stromal-low subgroup (P = 0.011). The discrimination ability of TSR was not less than the TNM staging system and was better in patients with stages I and II GC. We integrated the TSR parameter into the TNM staging system and proposed a new TSNM staging system creatively. There were three new subgroups (IC, IIC, IIID). There were four major groups and 10 subgroups in the TSNM system. The difference in overall survival (OS) was statistically significant among all TSNM system (P < 0.005 for all). Deep analyses revealed well predictive performance of the TSNM (P < 0.001). This study confirms the TSR as a TME prognostic factor for GC. TSR is a candidate TME parameter that could easily be implemented in routine pathology diagnostics, and the TSNM staging system has been established to optimize risk stratification for GC. The value of the TSNM staging system should be validated in further prospective study.

Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems.

PubMed

Cho, S-J; Choi, I J; Kook, M-C; Nam, B-H; Kim, C G; Lee, J Y; Ryu, K W; Kim, Y-W

2013-11-01

Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. To validate the OLGA and OLGIM staging systems in a region with high risk of GC. This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P < 0.001), particularly among patients with intestinal-type GCs (62.2%) compared with diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer. © 2013 John Wiley & Sons Ltd.

Revised Tubiana’s Staging System for Assessment of Disease Severity in Dupuytren’s Disease—Preliminary Clinical Findings

PubMed Central

Hindocha, Sandip; Stanley, John K.; Watson, James Stewart

2007-01-01

There are few objective staging systems to assess severity of Dupuytren’s disease (DD). Previous methods to assess severity of DD were based primarily on the degree of contracture of an affected digit measured using a goniometer. Nonetheless, this method of assessment alone may be incomplete, and other factors should be considered. White (n = 92) patients diagnosed with DD from northwest of England were assessed for DD. Objective criteria for evaluating severity incorporated quantified variables. The revised severity stage was correlated to a known staging system of DD (Tubiana’s staging system) which measures total flexion deformity for a single affected digit. Total revised severity staging scores ranged between 4 and 53 (mean = 18.7) and revealed significant positive correlation to Tubiana’s original staging system (r2 = 0.8, p < 0.001). There was significant difference between severity staging scores in those with a positive family history compared to those without (p < 0.01). In current practice, often, the degree of contracture in an affected digit is used solely as a measure of disease severity. Additional objective clinical information may provide useful prognostic indices for disease progression as well as postoperative outcome. PMID:18780081

Clinical diagnosis and staging of cholangiocarcinoma

PubMed Central

Blechacz, Boris; Komuta, Mina; Roskams, Tania; Gores, Gregory J.

2012-01-01

Cholangiocarcinoma is the most frequent biliary malignancy. It is difficult to diagnose owing to its anatomic location, growth patterns and lack of definite diagnostic criteria. Currently, cholangiocarcinoma is classified into the following types according to its anatomic location along the biliary tree: intrahepatic, perihilar or distal extrahepatic cholangiocarcinoma. These cholangiocarcinoma types differ in their biological behavior and management. The appropriate stratification of patients with regard to the anatomic location and stage of cholangiocarcinoma is a key determinate in their management. Staging systems can guide this stratification and provide prognostic information. In addition, staging systems are essential in order to compare and contrast the outcomes of different therapeutic approaches. A number of staging systems exist for cholangiocarcinoma—several early ones have been updated, and new ones are being developed. We discuss the emerging diagnostic criteria as well as the different staging systems for cholangiocarcinoma, and provide a critical appraisal regarding these advances in biliary tract malignancies. PMID:21808282

W.a.w (we are watching) smart app: accommodating social perception towards public officers’ performance

NASA Astrophysics Data System (ADS)

Widhoyoko, S. A.; Sasmoko; Nasir, L. A.; Manalu, S. R.; Indrianti, Y.

2018-03-01

This research is a continuation of previous research that is corruption early prevention is expanded by using expert system to analyze data and produce information to build decision. The research method used is neuroresearch method through three stages of research, namely exploratory stage, explanatory stage and confirmatory stages. The exploratory research finds W.aW’s Principles and W.a.W’s Units of Assessment as the basis for the preparation of the application. Stages of explanatory research in the form of W.a.W’s design of IT and confirmatory research stages are the design of expert system W.a.W. Expert System uses this formulation to generate dynamic standard value for each category and current social perception.

Effect of Operating Parameters on a Dual-Stage High Velocity Oxygen Fuel Thermal Spray System

NASA Astrophysics Data System (ADS)

Khan, Mohammed N.; Shamim, Tariq

2014-08-01

High velocity oxygen fuel (HVOF) thermal spray systems are being used to apply coatings to prevent surface degradation. The coatings of temperature sensitive materials such as titanium and copper, which have very low melting points, cannot be applied using a single-stage HVOF system. Therefore, a dual-stage HVOF system has been introduced and modeled computationally. The dual-spray system provides an easy control of particle oxidation by introducing a mixing chamber. In addition to the materials being sprayed, the thermal spray coating quality depends to a large extent on flow behavior of reacting gases and the particle dynamics. The present study investigates the influence of various operating parameters on the performance of a dual-stage thermal spray gun. The objective is to develop a predictive understanding of various parameters. The gas flow field and the free jet are modeled by considering the conservation of mass, momentum, and energy with the turbulence and the equilibrium combustion sub models. The particle phase is decoupled from the gas phase due to very low particle volume fractions. The results demonstrate the advantage of a dual-stage system over a single-stage system especially for the deposition of temperature sensitive materials.

Treatment of natural rubber processing wastewater using a combination system of a two-stage up-flow anaerobic sludge blanket and down-flow hanging sponge system.

PubMed

Tanikawa, D; Syutsubo, K; Hatamoto, M; Fukuda, M; Takahashi, M; Choeisai, P K; Yamaguchi, T

2016-01-01

A pilot-scale experiment of natural rubber processing wastewater treatment was conducted using a combination system consisting of a two-stage up-flow anaerobic sludge blanket (UASB) and a down-flow hanging sponge (DHS) reactor for more than 10 months. The system achieved a chemical oxygen demand (COD) removal efficiency of 95.7% ± 1.3% at an organic loading rate of 0.8 kg COD/(m(3).d). Bacterial activity measurement of retained sludge from the UASB showed that sulfate-reducing bacteria (SRB), especially hydrogen-utilizing SRB, possessed high activity compared with methane-producing bacteria (MPB). Conversely, the acetate-utilizing activity of MPB was superior to SRB in the second stage of the reactor. The two-stage UASB-DHS system can reduce power consumption by 95% and excess sludge by 98%. In addition, it is possible to prevent emissions of greenhouse gases (GHG), such as methane, using this system. Furthermore, recovered methane from the two-stage UASB can completely cover the electricity needs for the operation of the two-stage UASB-DHS system, accounting for approximately 15% of the electricity used in the natural rubber manufacturing process.

Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer

ClinicalTrials.gov

2014-09-09

Atypical Endometrial Hyperplasia; Endometrial Adenocarcinoma; Recurrent Endometrial Carcinoma; Stage IA Endometrial Carcinoma; Stage IB Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

Design of nonimaging concentrators as second stages in tandem with image-forming first-stage concentrators

NASA Technical Reports Server (NTRS)

Winston, R.; Welford, W. T.

1980-01-01

The paper discusses the paraboloidal mirror as a tracking solar concentrator, fitting a nonimaging second stage to the paraboloidal mirror, other image-forming systems as first stages, and tracking systems in two-dimensional geometry. Because of inherent aberrations, the paraboloidal mirror cannot achieve the thermodynamic limit. It is shown how paraboloidal mirrors of short focal ratio and similar systems can have their flux concentration enhanced to near the thermodynamic limit by the addition of nonimaging compound elliptical concentrators.

Design of nonimaging concentrators as second stages in tandem with image-forming first-stage concentrators

NASA Astrophysics Data System (ADS)

Winston, R.; Welford, W. T.

1980-02-01

The paper discusses the paraboloidal mirror as a tracking solar concentrator, fitting a nonimaging second stage to the paraboloidal mirror, other image-forming systems as first stages, and tracking systems in two-dimensional geometry. Because of inherent aberrations, the paraboloidal mirror cannot achieve the thermodynamic limit. It is shown how paraboloidal mirrors of short focal ratio and similar systems can have their flux concentration enhanced to near the thermodynamic limit by the addition of nonimaging compound elliptical concentrators.

An expert system based on principal component analysis, artificial immune system and fuzzy k-NN for diagnosis of valvular heart diseases.

PubMed

Sengur, Abdulkadir

2008-03-01

In the last two decades, the use of artificial intelligence methods in medical analysis is increasing. This is mainly because the effectiveness of classification and detection systems have improved a great deal to help the medical experts in diagnosing. In this work, we investigate the use of principal component analysis (PCA), artificial immune system (AIS) and fuzzy k-NN to determine the normal and abnormal heart valves from the Doppler heart sounds. The proposed heart valve disorder detection system is composed of three stages. The first stage is the pre-processing stage. Filtering, normalization and white de-noising are the processes that were used in this stage. The feature extraction is the second stage. During feature extraction stage, wavelet packet decomposition was used. As a next step, wavelet entropy was considered as features. For reducing the complexity of the system, PCA was used for feature reduction. In the classification stage, AIS and fuzzy k-NN were used. To evaluate the performance of the proposed methodology, a comparative study is realized by using a data set containing 215 samples. The validation of the proposed method is measured by using the sensitivity and specificity parameters; 95.9% sensitivity and 96% specificity rate was obtained.

Bilateral Total Hip Arthroplasty: 1-Stage or 2-Stage? A Meta-Analysis.

PubMed

Shao, Hongyi; Chen, Chi-Lung; Maltenfort, Mitchell G; Restrepo, Camilo; Rothman, Richard H; Chen, Antonia F

2017-02-01

Total hip arthroplasty (THA) is one of the most successful orthopedic surgeries performed in the last 50 years. However, controversies still exist between conducting 1- or 2-stage bilateral THA. Using PubMed, Ovid, Embase, and Cochrane library databases, we searched for papers written between January 1995 and October 2015 that contained the following search terms: "one-stage or two-stage" or "simultaneous or staged," and "hip" and "arthroplasty or replacement." A meta-analysis was conducted with the collected pooled data about major and minor systemic complications, surgical complications, and other perioperative data associated with 1- and 2-stage bilateral THA. Statistical analysis was performed by the Mantel-Haenszel method, and the fixed effect model was used to analyze data. There were 13 studies with 17,762 patients who underwent 1-stage bilateral THA and 46,147 patients who underwent 2-stage bilateral THA. One-stage bilateral THA had a lower risk of major systemic complications, less deep venous thrombosis, and shorter operative time compared with 2-stage bilateral THA. There were no significant differences in death, pulmonary embolism, cardiovascular complication, infections, minor complications, and other surgical complications between procedures. One-stage bilateral THA was superior to 2-stage bilateral THA in terms of major systemic complication, deep venous thrombosis, and surgical time compared with 2-stage bilateral THA. However, this study does not encourage performing 1-stage over 2-stage bilateral THA. Higher evidence level studies are necessary for further analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

Rocket nozzle expansion ratio analysis for dual-fuel earth-to-orbit vehicles

NASA Technical Reports Server (NTRS)

Martin, James A.

1989-01-01

Results are reported from a recent study of the effects of Space Shuttle Main Engine expansion ratio modifications, in the cases of both single-stage and two-stage systems. Two-position nozzles were employed; after varying the lower expansion ratio while the higher was held constant at 120, the lower expansion ratio was held constant at 40 or 60 while the higher expansion ratio was varied. The expansion ratios for minimum vehicle dry mass are different for single-stage and two-stage systems. For two-stage systems, a single expansion ratio of 77.5 provides a lower dry mass than any two-position nozzle.

[Coupling coordinated development of ecological-economic system in Loess Plateau].

PubMed

Zhang, Qing-Feng; Wu, Fa-Qi; Wang, Li; Wang, Jian

2011-06-01

Based on system theory, a coupling coordinated development model of ecological-economic system in Loess Plateau was established, and the evaluation criteria and basic types of the coordinated development of the ecological-economic system were proposed. The county-level coupling coordinated development of the ecological-economic system was also discussed, based on the local characteristics. The interactions between the ecological and economic systems in Loess Plateau could be divided into four stages, i.e., seriously disordered development stage, mild-disordered development stage, low-level coordinated development stage, and high level well-coordinated development stage. At each stage, there existed a cyclic process of profit and loss-antagonist-running-dominant-synchronous development. The coupling development degree of the ecological-economic system in Loess Plateau was overall at a lower level, being about 62.7% of the counties at serious disorder, 30.1% of the counties at mild disorder, and 7.1% of the counties at low but coordinated level. The coupling development degree based on the model established in this study could better reflect the current social-economic and ecological environment situations, especially the status of coordination. To fully understand the coupling of ecological-economic system and to adopt appropriate development mode would be of significance to promote the county-level coordinated development in Loess Plateau.

Developmental Flight Instrumentation System for the Crew Launch Vehicle

NASA Technical Reports Server (NTRS)

Crawford, Kevin; Thomas, John

2006-01-01

The National Aeronautics and Space Administration is developing a new launch vehicle to replace the Space Shuttle. The Crew Launch Vehicle (CLV) will be a combination of new design hardware and heritage Apollo and Space Shuttle hardware. The current CLV configuration is a 5 segment solid rocket booster first stage and a new upper stage design with a modified Apollo era J-2 engine. The current schedule has two test flights with a first stage and a structurally identical, but without engine, upper stage. Then there will be two more test flights with a full complement of flight hardware. After the completion of the test flights, the first manned flight to the International Space Station is scheduled for late 2012. To verify the CLV's design margins a developmental flight instrumentation (DFI) system is needed. The DFI system will collect environmental and health data from the various CLV subsystem's and either transmit it to the ground or store it onboard for later evaluation on the ground. The CLV consists of 4 major elements: the first stage, the upper stage, the upper stage engine and the integration of the first stage, upper stage and upper stage engine. It is anticipated that each of CLVs elements will have some version of DFI. This paper will discuss a conceptual DFI design for each element and also of an integrated CLV DFI system.

Prognostic significance of combined albumin-bilirubin and tumor-node-metastasis staging system in patients who underwent hepatic resection for hepatocellular carcinoma.

PubMed

Harimoto, Norifumi; Yoshizumi, Tomoharu; Sakata, Kazuhito; Nagatsu, Akihisa; Motomura, Takashi; Itoh, Shinji; Harada, Noboru; Ikegami, Toru; Uchiyama, Hideaki; Soejima, Yuji; Maehara, Yoshihiko

2017-11-01

In recent years, the establishment of new staging systems for hepatocellular carcinoma (HCC) has been reported worldwide. The system combining albumin-bilirubin (ALBI) with tumor-node-metastasis stage, developed by the Liver Cancer Study Group of Japan, was called the ALBI-T score. Patient data were retrospectively collected for 357 consecutive patients who had undergone hepatic resection for HCC with curative intent between January 2004 and December 2015. The overall survival and recurrence-free survival were compared by the Kaplan-Meier method, using different staging systems: the Japan integrated staging (JIS), modified JIS, and ALBI-T. Multivariate analysis identified five poor prognostic factors (higher age, poor differentiation, the presence of microvascular invasion, the presence of intrahepatic metastasis, and blood transfusion) that influenced overall survival, and four poor prognostic factors (the presence of intrahepatic metastasis, serum α-fetoprotein level, blood transfusion, and each staging system (JIS, modified JIS, and ALBI-T score)) that influenced recurrence-free survival. Patients for each these three staging system had a significantly worse prognosis regarding recurrence-free survival, but not with overall survival. The modified JIS score showed the lowest Akaike information criteria statistic value, indicating it had the best ability to predict overall survival compared with the other staging systems. This retrospective analysis showed that, in post-hepatectomy patients with HCC, the ALBI-T score is predictive of worse recurrence-free survival, even when adjustments are made for other known predictors. However, modified JIS is better than ALBI-T in predicting overall survival. © 2017 The Japan Society of Hepatology.

Multistage position-stabilized vibration isolation system for neutron interferometry

NASA Astrophysics Data System (ADS)

Arif, Muhammad; Brown, Dennis E.; Greene, Geoffrey L.; Clothier, R.; Littrell, K.

1994-10-01

A two stage, position stabilized vibration isolation system has been constructed and is now in operation at the Cold Neutron Research Facility of the National Institute of Standards and Technology, Gaithersburg, MD. The system employs pneumatic isolators with a multiple input/multiple output pneumatic servo system based upon pulse width modulation control loops. The first stage consists of a 40,000 kg reinforced concrete table supported by pneumatic isolators. A large environmentally isolated laboratory enclosure rests on the concrete table. The second stage consists of a 3000 kg granite optical table located within the enclosure and supported by another set of pneumatic isolators. The position of the two stages is monitored by proximity sensors and inclinometers with 12 degrees of freedom. The system controls 12 independent pneumatic airsprings. The signals from these sensors are fed into a personal computer based control system. The control system has maintained the position of the two stages to better than 1 micrometers in translation and 5 (mu) rad in orientation for a period of a few months. A description of the system and its characteristics is given.

Comprehensive Approach to Pupil Planning: Stage I - Classroom Support (Includes Classroom Support Procedures). Experimental Edition.

ERIC Educational Resources Information Center

Mabry, Ann; Kaufman, Martin J.

Presented is Stage I of the Comprehensive Approach to Pupil Planning (CAPP) System, a three-stage model for planning educational interventions in the regular and special education classrooms and for guiding placement decisions. The guide consists of the following: an overview of the CAPP System; an introduction to Stage I on classroom support…

Effects of gear box vibration and mass imbalance on the dynamics of multi-stage gear transmissions

NASA Technical Reports Server (NTRS)

Choy, Fred K.; Tu, Yu K.; Zakrajsek, James J.; Townsend, Dennis P.

1991-01-01

The dynamic behavior of multistage gear transmission system, with the effects of gear-box-induced vibrations and rotor mass-imbalances is analyzed. The model method, using undamped frequencies and planar mode shapes, is used to reduce the degree-of-freedom of the system. The various rotor-bearing stages as well as lateral and torsional vibrations of each individual stage are coupled through localized gear-mesh-tooth interactions. Gear-box vibrations are coupled to the gear stage dynamics through bearing support forces. Transient and steady state dynamics of lateral and torsional vibrations of the geared system are examined in both time and frequency domain. A typical three-staged geared system is used as an example. Effects of mass-imbalance and gear box vibrations on the system dynamic behavior are presented in terms of modal excitation functions for both lateral and torsional vibrations. Operational characteristics and conclusions are drawn from the results presented.

Successful Pregnancy Using the NxStage Home Hemodialysis System

PubMed Central

Brahmbhatt, Yasmin; Ikeme, Arinze; Bhogal, Navjyot; Berghella, Vincenzo

2016-01-01

Pregnancy in the setting of the uremic milieu of renal disease has a lower success rate than in the normal population and is a rare event. While intensified renal replacement therapy (RRT) during pregnancy can lead to improved outcomes, most studies have focused on nocturnal hemodialysis as the main RRT in pregnancy. Although thousands of patients use the home NxStage System One short daily hemodialysis (SDHD) machine in the United States, pregnancy outcomes with this therapy are unknown. The NxStage System One uses low-volume dialysate and hence small and middle molecule clearance may differ compared to conventional therapies and affect pregnancy outcomes. We report a case of a successful conception and pregnancy using the home NxStage system. The NxStage system may provide an alternative to the more routinely used NHD or standard SDHD therapies for women of childbearing age. PMID:26949554

Cryogenic refrigeration apparatus

DOEpatents

Crunkleton, James A.

1992-01-01

A technique for producing a cold environment in a refrigerant system in which input fluid from a compressor at a first temperature is introduced into an input channel of the system and is pre-cooled to a second temperature for supply to one of at least two stages of the system, and to a third temperature for supply to another stage thereof. The temperatures at such stages are reduced to fourth and fifth temperatures below the second and third temperatures, respectively. Fluid at the fourth temperature from the one stage is returned through the input channel to the compressor and fluid at the fifth temperature from the other stage is returned to the compressor through an output channel so that pre-cooling of the input fluid to the one stage occurs by regenerative cooling and counterflow cooling and pre-cooling of the input fluid to the other stage occurs primarily by counterflow cooling.

Cryogenic refrigeration apparatus

DOEpatents

Crunkleton, J.A.

1992-03-31

A technique for producing a cold environment in a refrigerant system in which input fluid from a compressor at a first temperature is introduced into an input channel of the system and is pre-cooled to a second temperature for supply to one of at least two stages of the system, and to a third temperature for supply to another stage thereof. The temperatures at such stages are reduced to fourth and fifth temperatures below the second and third temperatures, respectively. Fluid at the fourth temperature from the one stage is returned through the input channel to the compressor and fluid at the fifth temperature from the other stage is returned to the compressor through an output channel so that pre-cooling of the input fluid to the one stage occurs by regenerative cooling and counterflow cooling and pre-cooling of the input fluid to the other stage occurs primarily by counterflow cooling. 6 figs.

Evaluation of the 8th AJCC staging system for pathologically versus clinically staged pancreatic adenocarcinoma: A time to revisit a dogma?

PubMed

Abdel-Rahman, Omar

2018-02-01

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic exocrine adenocarcinoma has been released. The current study seeks to assess the 7th and 8th editions among patients registered within the surveillance, epidemiology and end results (SEER) database. SEER database (2010-2013) has been accessed through SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the collaborative stage descriptions. Kaplan-Meier analysis of overall survival and pancreatic cancer-specific survival analyses (according to both 7th and 8th editions and according to whether pathological or clinical staging were conducted) has been performed. Multivariate analysis of factors affecting pancreatic cancer-specific survival was also conducted through a Cox proportional hazard model. A total of 18  948 patients with pancreatic adenocarcinoma were identified in the period from 2010-2013. Pancreatic cancer-specific survival among pathologically staged patients and according to the 8th edition showed significant differences for all pair wise comparisons among different stages (P < 0.0001) except for the comparison between stage IA and stage IB (P = 0.307) and the comparison between stage IB and stage IIA (P = 0.116). Moreover, P value for stage IA vs IIA was 0.014; while pancreatic cancer-specific survival according to the 7th edition among pathologically staged patients showed significant differences for all pair wise comparisons among different stages (P < 0.0001) except for the comparison between IA and IB (P = 0.072), the comparison between stage IIA and stage IIB (P = 0.065), the comparison between stage IIA and stage III (P = 0.059) and the comparison between IIB and III (P = 0.595). Among clinically staged patients (i.e. those who did not undergo initial radical surgery), the prognostic performance of both 7th and 8th stages for both overall survival and pancreatic cancer-specific survival was limited. There is clearly a need to have two staging systems for pancreatic adenocarcinoma: pathological and clinical staging systems. Copyright © 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.

CRYOGENIC UPPER STAGE SYSTEM SAFETY

NASA Technical Reports Server (NTRS)

Smith, R. Kenneth; French, James V.; LaRue, Peter F.; Taylor, James L.; Pollard, Kathy (Technical Monitor)

2005-01-01

NASA s Exploration Initiative will require development of many new systems or systems of systems. One specific example is that safe, affordable, and reliable upper stage systems to place cargo and crew in stable low earth orbit are urgently required. In this paper, we examine the failure history of previous upper stages with liquid oxygen (LOX)/liquid hydrogen (LH2) propulsion systems. Launch data from 1964 until midyear 2005 are analyzed and presented. This data analysis covers upper stage systems from the Ariane, Centaur, H-IIA, Saturn, and Atlas in addition to other vehicles. Upper stage propulsion system elements have the highest impact on reliability. This paper discusses failure occurrence in all aspects of the operational phases (Le., initial burn, coast, restarts, and trends in failure rates over time). In an effort to understand the likelihood of future failures in flight, we present timelines of engine system failures relevant to initial flight histories. Some evidence suggests that propulsion system failures as a result of design problems occur shortly after initial development of the propulsion system; whereas failures because of manufacturing or assembly processing errors may occur during any phase of the system builds process, This paper also explores the detectability of historical failures. Observations from this review are used to ascertain the potential for increased upper stage reliability given investments in integrated system health management. Based on a clear understanding of the failure and success history of previous efforts by multiple space hardware development groups, the paper will investigate potential improvements that can be realized through application of system safety principles.

Expendable Second Stage Reusable Space Shuttle Booster. Volume 9; Preliminary System Specification

NASA Technical Reports Server (NTRS)

1971-01-01

The specification for establishing the requirements for the system performance, design, development, and ground and flight operations of the expendable second stage on a reusable space shuttle booster system is presented. The basic specification is that the system shall be capable of placing payloads in excess of 100,000 pounds into earth orbit. In addition, the expendable second stage provides a multimission, economical, large capability system suitable for a variety of space missions in the 1980 time period.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The model is designed to enable decision makers to compare the economics of geothermal projects with the economics of alternative energy systems at an early stage in the decision process. The geothermal engineering and economic feasibility computer model (GEEF) is written in FORTRAN IV language and can be run on a mainframe or a mini-computer system. An abbreviated version of the model is being developed for usage in conjunction with a programmable desk calculator. The GEEF model has two main segments, namely (i) the engineering design/cost segment and (ii) the economic analysis segment. In the engineering segment, the model determinesmore » the numbers of production and injection wells, heat exchanger design, operating parameters for the system, requirement of supplementary system (to augment the working fluid temperature if the resource temperature is not sufficiently high), and the fluid flow rates. The model can handle single stage systems as well as two stage cascaded systems in which the second stage may involve a space heating application after a process heat application in the first stage.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makarov, Pavel V., E-mail: pvm@ispms.tsc.ru

An evolutionary approach to earthquake development is proposed. A medium under loading is treated as a multiscale nonlinear dynamic system. Its failure involves a number of stages typical of any dynamic system: dynamic chaos, self-organized criticality, and global stability loss in the final stage of its evolution. In the latter stage, the system evolves in a blow-up mode accompanied by catastrophic superfast movements of the elements of this geomedium.

Analysis of the staging maneuver and booster glideback guidance for a two-stage, winged, fully reusable launch vehicle. M.S. Thesis - George Washington Univ.

NASA Technical Reports Server (NTRS)

Naftel, J. Christopher; Powell, Richard W.

1993-01-01

One of the promising launch concepts that could replace the current space shuttle launch system is a two-stage, winged, vertical-takeoff, fully reusable launch vehicle. During the boost phase of ascent, the booster provides propellant for the orbiter engines through a cross-feed system. When the vehicle reaches a Mach number of 3, the booster propellants are depleted and the booster is staged and glides unpowered to a horizontal landing at a launch site runway. Two major design issues for this class of vehicle are the staging maneuver and the booster glideback. For the staging maneuver analysis, a technique was developed that provides for a successful separation of the booster from the orbiter over a wide range of staging angles of attack. A longitudinal flight control system was developed for control of the booster during the staging maneuver. For the booster glide back analysis, a guidance algorithm was developed that successfully guides the booster from the completion of the staging maneuver to a launch site runway while encountering many off-nominal atmospheric, aerodynamic, and staging conditions.

Optimization of a Two Stage Pulse Tube Refrigerator for the Integrated Current Lead System

NASA Astrophysics Data System (ADS)

Maekawa, R.; Matsubara, Y.; Okada, A.; Takami, S.; Konno, M.; Tomioka, A.; Imayoshi, T.; Hayashi, H.; Mito, T.

2008-03-01

Implementation of a conventional current lead with a pulse tube refrigerator has been validated to be working as an Integrated Current Lead (ICL) system for the Superconducting Magnetic Energy Storage (SMES). Realization of the system is primarily accounted for the flexibility of a pulse tube refrigerator, which does not posses any mechanical piston and/or displacer. As for an ultimate version of the ICL system, a High Temperature Superconducting (HTS) lead links a superconducting coil with a conventional copper lead. To ensure the minimization of heat loads to the superconducting coil, a pulse tube refrigerator has been upgraded to have a second cooling stage. This arrangement reduces not only the heat loads to the superconducting coil but also the operating cost for a SMES system. A prototype two-stage pulse tube refrigerator, series connected arrangement, was designed and fabricated to satisfy the requirements for the ICL system. Operation of the first stage refrigerator is a four-valve mode, while the second stage utilizes a double inlet configuration to ensure its confined geometry. The paper discusses the optimization of second stage cooling to validate the conceptual design

Staging - SEER Registrars

Cancer.gov

Access tools for coding Extent of Disease 2018, plus Summary Staging Manual 2000, resources for comparison and mapping between staging systems, UICC information, and Collaborative Stage instructions and software.

Performance assessment and microbial diversity of two pilot scale multi-stage sub-surface flow constructed wetland systems.

PubMed

Babatunde, A O; Miranda-CasoLuengo, Raul; Imtiaz, Mehreen; Zhao, Y Q; Meijer, Wim G

2016-08-01

This study assessed the performance and diversity of microbial communities in multi-stage sub-surface flow constructed wetland systems (CWs). Our aim was to assess the impact of configuration on treatment performance and microbial diversity in the systems. Results indicate that at loading rates up to 100gBOD5/(m(2)·day), similar treatment performances can be achieved using either a 3 or 4 stage configuration. In the case of phosphorus (P), the impact of configuration was less obvious and a minimum of 80% P removal can be expected for loadings up to 10gP/(m(2)·day) based on the performance results obtained within the first 16months of operation. Microbial analysis showed an increased bacterial diversity in stage four compared to the first stage. These results indicate that the design and configuration of multi-stage constructed wetland systems may have an impact on the treatment performance and the composition of the microbial community in the systems, and such knowledge can be used to improve their design and performance. Copyright © 2016. Published by Elsevier B.V.

Multi-Stage System for Automatic Target Recognition

NASA Technical Reports Server (NTRS)

Chao, Tien-Hsin; Lu, Thomas T.; Ye, David; Edens, Weston; Johnson, Oliver

2010-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an artificial neural network classifier. The multi-stage system allows tuning the detection sensitivity and the identification specificity individually in each stage. It is easier to achieve optimized ATR operation based on its specific goal. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar and video image datasets.

LOX/LH2 propulsion system for launch vehicle upper stage, test results

NASA Technical Reports Server (NTRS)

Ikeda, T.; Imachi, U.; Yuzawa, Y.; Kondo, Y.; Miyoshi, K.; Higashino, K.

1984-01-01

The test results of small LOX/LH2 engines for two propulsion systems, a pump fed system and a pressure fed system are reported. The pump fed system has the advantages of higher performances and higher mass fraction. The pressure fed system has the advantages of higher reliability and relative simplicity. Adoption of these cryogenic propulsion systems for upper stage of launch vehicle increases the payload capability with low cost. The 1,000 kg thrust class engine was selected for this cryogenic stage. A thrust chamber assembly for the pressure fed propulsion system was tested. It is indicated that it has good performance to meet system requirements.

The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

PubMed Central

Lu, Jing; Lu, Jin; Liu, Aijun; Fu, Weijun; Du, Juan; Huang, Xiaojun; Chen, Wenming; Hou, Jian

2015-01-01

The International Staging System (ISS) is the most important prognostic system for multiple myeloma (MM). It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS) of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p < 0.001), and the median progression-free survival (PFS) was 30/29.5/25 months (p = 0.072), respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system. PMID:26640799

Comprehensive Approach to Pupil Planning: Stage III - Instructional Planning (Includes Data Sources Within the CAPP System and Teacher's Instructional Plan). Experimental Edition.

ERIC Educational Resources Information Center

Vlasak, Frances Stetson; Kaufman, Martin J.

Presented is Stage III of the Comprehensive Approach to Pupil Planning (CAPP) System, a three-stage model for planning educational interventions in the regular and special education classrooms and for guiding placement decisions. The guide focuses on the instructional planning team with sections on the following: Stage III personnel; roles and…

Performances of single and two-stage pulse tube cryocoolers under different vacuum levels with and without thermal radiation shields

NASA Astrophysics Data System (ADS)

Kasthurirengan, Srinivasan; Behera, Upendra; Nadig, D. S.; Krishnamoorthy, V.

2012-06-01

Single and two-stage Pulse Tube Cryocoolers (PTC) have been designed, fabricated and experimentally studied. The single stage PTC reaches a no-load temperature of ~ 29 K at its cold end, the two-stage PTC reaches ~ 2.9 K in its second stage cold end and ~ 60 K in its first stage cold end. The two-stage Pulse Tube Cryocooler provides a cooling power of ~ 250 mW at 4.2 K. The single stage system uses stainless steel meshes along with Pb granules as its regenerator materials, while the two-stage PTC uses combinations of Pb along with Er3Ni / HoCu2 as the second stage regenerator materials. Normally, the above systems are insulated by thermal radiation shields and mounted inside a vacuum chamber which is maintained at high vacuum. To evaluate the performance of these systems in the possible conditions of loss of vacuum with and without radiation shields, experimental studies have been performed. The heat-in-leak under such severe conditions has been estimated from the heat load characteristics of the respective stages. The experimental results are analyzed to obtain surface emissivities and effective thermal conductivities as a function of interspace pressure.

Use of real time gas production data for more accurate comparison of continuous single-stage and two-stage fermentation.

PubMed

Massanet-Nicolau, Jaime; Dinsdale, Richard; Guwy, Alan; Shipley, Gary

2013-02-01

Changes in fermenter gas composition within a given 24h period can cause severe bias in calculations of biogas or energy yields based on just one or two measurements of gas composition per day, as is common in other studies of two-stage fermentation. To overcome this bias, real time recording of gas composition and production were used to undertake a detailed and controlled comparison of single-stage and two-stage fermentation using a real world substrate (wheat feed pellets). When a two-stage fermentation system was used, methane yields increased from 261 L kg(-1)VS using a 20 day HRT, single-stage fermentation, to 359 L kg(-1) VS using a two-stage fermentation with the same overall retention time--an increase of 37%. Additionally a hydrogen yield of 7 L kg(-1) VS was obtained when two-stage fermentation was used. The two-stage system could also be operated at a shorter, 12 day HRT and still produce higher methane yields (306 L kg(-1) VS). Both two-stage fermentation systems evaluated exhibited methane yields in excess of that predicted by a biological methane potential test (BMP) performed using the same feedstock (260 L kg(-1)VS). Copyright © 2012 Elsevier Ltd. All rights reserved.

Abnormal Uterine Bleeding.

PubMed

Benetti-Pinto, Cristina Laguna; Rosa-E-Silva, Ana Carolina Japur de Sá; Yela, Daniela Angerame; Soares Júnior, José Maria

2017-07-01

Abnormal uterine bleeding is a frequent condition in Gynecology. It may impact physical, emotional sexual and professional aspects of the lives of women, impairing their quality of life. In cases of acute and severe bleeding, women may need urgent treatment with volumetric replacement and prescription of hemostatic substances. In some specific cases with more intense and prolonged bleeding, surgical treatment may be necessary. The objective of this chapter is to describe the main evidence on the treatment of women with abnormal uterine bleeding, both acute and chronic. Didactically, the treatment options were based on the current International Federation of Gynecology and Obstetrics (FIGO) classification system (PALM-COEIN). The etiologies of PALM-COEIN are: uterine Polyp (P), Adenomyosis (A), Leiomyoma (L), precursor and Malignant lesions of the uterine body (M), Coagulopathies (C), Ovulatory dysfunction (O), Endometrial dysfunction (E), Iatrogenic (I), and Not yet classified (N). The articles were selected according to the recommendation grades of the PubMed, Cochrane and Embase databases, and those in which the main objective was the reduction of uterine menstrual bleeding were included. Only studies written in English were included. All editorial or complete papers that were not consistent with abnormal uterine bleeding, or studies in animal models, were excluded. The main objective of the treatment is the reduction of menstrual flow and morbidity and the improvement of quality of life. It is important to emphasize that the treatment in the acute phase aims to hemodynamically stabilize the patient and stop excessive bleeding, while the treatment in the chronic phase is based on correcting menstrual dysfunction according to its etiology and clinical manifestations. The treatment may be surgical or pharmacological, and the latter is based mainly on hormonal therapy, anti-inflammatory drugs and antifibrinolytics. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

The Malemute development program. [rocket upper stage engine design

NASA Technical Reports Server (NTRS)

Bolster, W. J.; Hoekstra, P. W.

1976-01-01

The Malemute vehicle systems are two-stage systems based on utilizing a new high performance upper stage motor with two existing military boosters. The Malmute development program is described relative to program structure, preliminary design, vehicle subsystems, and the Malemute motor. Two vehicle systems, the Nike-Malemute and Terrier-Malemute, were developed which are capable of transporting comparatively large diameter (16 in.) 200-lb payloads to altitudes of 500 and 700 km, respectively. These vehicles provide relatively low-cost transportation with two-stage reliability and launch simplicity. Flight tests of both vehicle systems revealed their performance capabilities, with the Terrier-Malemute system involving a unique Malemute motor spin sensitivity problem. It is suggested that the vehicles can be successfully flown by lowering the burnout spin rate.

Systems Support Mapping in Guiding Self-Management in Stage I-III Colorectal Cancer Survivors

ClinicalTrials.gov

2018-05-30

Cancer Survivor; Stage I Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage IIA Colorectal Cancer AJCC v8; Stage IIB Colorectal Cancer AJCC v8; Stage IIC Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8

Ares First Stage "Systemology" - Combining Advanced Systems Engineering and Planning Tools to Assure Mission Success

NASA Technical Reports Server (NTRS)

Seiler, James; Brasfield, Fred; Cannon, Scott

2008-01-01

Ares is an integral part of NASA s Constellation architecture that will provide crew and cargo access to the International Space Station as well as low earth orbit support for lunar missions. Ares replaces the Space Shuttle in the post 2010 time frame. Ares I is an in-line, two-stage rocket topped by the Orion Crew Exploration Vehicle, its service module, and a launch abort system. The Ares I first stage is a single, five-segment reusable solid rocket booster derived from the Space Shuttle Program's reusable solid rocket motor. The Ares second or upper stage is propelled by a J-2X main engine fueled with liquid oxygen and liquid hydrogen. This paper describes the advanced systems engineering and planning tools being utilized for the design, test, and qualification of the Ares I first stage element. Included are descriptions of the current first stage design, the milestone schedule requirements, and the marriage of systems engineering, detailed planning efforts, and roadmapping employed to achieve these goals.

Method and apparatus for converting and removing organosulfur and other oxidizable compounds from distillate fuels, and compositions obtained thereby

DOEpatents

D'Alessandro, Robert N.; Tarabocchia, John; Jones, Jerald Andrew; Bonde, Steven E.; Leininger, Stefan

2010-10-26

The present disclosure is directed to a multi-stage system and a process utilizing said system with the design of reducing the sulfur-content in a liquid comprising hydrocarbons and organosulfur compounds. The process comprising at least one of the following states: (1) an oxidation stage; (2) an extraction state; (3) a raffinate washing stage; (4) a raffinate polishing stage; (5) a solvent recovery stage; (6) a solvent purification stage; and (7) a hydrocarbon recovery stage. The process for removing sulfur-containing hydrocarbons from gas oil, which comprises oxidizing gas oil comprising hydrocarbons and organosulfur compounds to obtain a product gas oil.

Evaluation of Bosch-Based Systems Using Non-Traditional Catalysts at Reduced Temperatures

NASA Technical Reports Server (NTRS)

Abney, Morgan B.; Mansell, J. Matthew

2011-01-01

Oxygen and water resupply make open loop atmosphere revitalization (AR) systems unfavorable for long-term missions beyond low Earth orbit. Crucial to closing the AR loop are carbon dioxide reduction systems with low mass and volume, minimal power requirements, and minimal consumables. For this purpose, NASA is exploring using Bosch-based systems. The Bosch process is favorable over state-of-the-art Sabatier-based processes due to complete loop closure. However, traditional operation of the Bosch required high reaction temperatures, high recycle rates, and significant consumables in the form of catalyst resupply due to carbon fouling. A number of configurations have been proposed for next-generation Bosch systems. First, alternative catalysts (catalysts other than steel wool) can be used in a traditional single-stage Bosch reactor to improve reaction kinetics and increase carbon packing density. Second, the Bosch reactor may be split into separate stages wherein the first reactor stage is dedicated to carbon monoxide and water formation via the reverse water-gas shift reaction and the second reactor stage is dedicated to carbon formation. A series system will enable maximum efficiency of both steps of the Bosch reaction, resulting in optimized operation and maximum carbon formation rate. This paper details the results of testing of both single-stage and two-stage Bosch systems with alternative catalysts at reduced temperatures. These results are compared to a traditional Bosch system operated with a steel wool catalyst.

Autonomous safety and reliability features of the K-1 avionics system

NASA Astrophysics Data System (ADS)

Mueller, George E.; Kohrs, Dick; Bailey, Richard; Lai, Gary

2004-03-01

Kistler Aerospace Corporation is developing the K-1, a fully reusable, two-stage-to-orbit launch vehicle. Both stages return to the launch site using parachutes and airbags. Initial flight operations will occur from Woomera, Australia. K-1 guidance is performed autonomously. Each stage of the K-1 employs a triplex, fault tolerant avionics architecture, including three fault tolerant computers and three radiation hardened Embedded GPS/INS units with a hardware voter. The K-1 has an Integrated Vehicle Health Management (IVHM) system on each stage residing in the three vehicle computers based on similar systems in commercial aircraft. During first-stage ascent, the IVHM system performs an Instantaneous Impact Prediction (IIP) calculation 25 times per second, initiating an abort in the event the vehicle is outside a predetermined safety corridor for at least 3 consecutive calculations. In this event, commands are issued to terminate thrust, separate the stages, dump all propellant in the first-stage, and initiate a normal landing sequence. The second-stage flight computer calculates its ability to reach orbit along its state vector, initiating an abort sequence similar to the first stage if it cannot. On a nominal mission, following separation, the second-stage also performs calculations to assure its impact point is within a safety corridor. The K-1's guidance and control design is being tested through simulation with hardware-in-the-loop at Draper Laboratory. Kistler's verification strategy assures reliable and safe operation of the K-1.

Sleep stage 2: an electroencephalographic, autonomic, and hormonal duality.

PubMed

Brandenberger, Gabrielle; Ehrhart, Jean; Buchheit, Martin

2005-12-01

It is generally thought that the electroencephalogram of sleep stage 2 is not uniform, depending on whether sleep stage 2 evolves toward slow-wave sleep (SWS) or toward rapid eye movement (REM) sleep. We provide here further evidence of the duality of sleep stage 2 on the basis of its autonomic and hormonal background. Fourteen healthy men (aged 21-29 years) underwent 1 experimental night. Sleep and cardiac recordings were taken from 11:00 PM to 7:00 AM. Blood was sampled continuously over 10-minute periods. Autonomic activity, as inferred from heart rate variability analysis and hormone profiles, were examined with regard to the normalized hypnograms. We found a dual activity of the autonomic nervous system during sleep stage 2, with a progressive decrease in heart rate variability sympathetic indexes during the transition toward SWS contrasting with high and rather stable levels during sleep stage 2 that evolve toward REM sleep. Also, different profiles were observed in 2 major hormone systems, the activating adrenocorticotropic system and the renin-angiotensin system. Cortisol, in its active period of circadian secretion, was stable during sleep stage 2 preceding SWS and increased significantly when sleep stage 2 preceded REM sleep. For plasma renin activity, sleep stage 2 played a transitional role, initiating increasing levels that peaked during SWS and decreasing levels that reached a nadir during REM sleep. These results indicate an autonomic and hormonal duality of sleep stage 2 that is characterized by a "quiet" period preparing SWS and an "active" period preceding REM sleep. These differences may confer a fundamental role on this sleep stage in ultradian sleep regulation.

Launching Payloads Into Orbit at Relatively Low Cost

NASA Technical Reports Server (NTRS)

Wilcox, Brian

2007-01-01

A report proposes the development of a system for launching payloads into orbit at about one-fifth the cost per unit payload weight of current systems. The PILOT system was a solid-fuel, aerodynamically spun and spin-stabilized, five-stage rocket with onboard controls including little more than an optoelectronic horizon sensor and a timer for triggering the second and fifth stages, respectively. The proposal calls for four improvements over the PILOT system to enable control of orbital parameters: (1) the aerodynamic tipover of the rocket at the top of the atmosphere could be modeled as a nonuniform gyroscopic precession and could be controlled by selection of the initial rocket configuration and launch conditions; (2) the attitude of the rocket at the top of the first-stage trajectory could be measured by use of radar tracking or differential Global Positioning System receivers to determine when to trigger the second stage; (3) the final-stage engines could be configured around the payload to enhance spin stabilization during a half-orbit coast up to apoapsis where the final stage would be triggered; and (4) the final payload stage could be equipped with a "beltline" of small thrusters for correcting small errors in the trajectory as measured by an off-board tracking subsystem.

40 CFR 63.746 - Standards: Depainting operations.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., or paragraph (c) where organic HAP are controlled using a control system. This section does not apply... filter system, three-stage filter system, or other control system equivalent to the three-stage filter... operation shall be reduced by the use of a control system. Each control system that was installed before the...