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Gynecologic Oncology

Organisations and Professional Societies
Specialist Journals
Recent Research Publications
Cervical Cancer
Endometrial (Uterus) Cancer
Fallopian Tube Cancer
Gestational Trophoblastic Cancer
Ovarian Cancer
Vaginal Cancer
Vulva Cancer
Uterine Sarcoma

Organisations and Professional Societies (32 links)

Specialist Journals (4 links)

See also: Oncology Journals

Recent Research Publications

Chudecka-Głaz A, Cymbaluk-Płoska A, Strojna A, Menkiszak J
HE4 Serum Levels in Patients with BRCA1 Gene Mutation Undergoing Prophylactic Surgery as well as in Other Benign and Malignant Gynecological Diseases.
Dis Markers. 2017; 2017:9792756 [PubMed] Free Access to Full Article Related Publications
Objective. We assess the behavior of serum concentrations of HE4 marker in female carriers of BRCA1 and assess the diagnostic usefulness of HE4 in ovarian and endometrial cancer. Methods. A total of 619 women with BRCA1 gene mutation, ovarian, endometrial, metastatic, other gynecological cancers, or benign gynecological diseases were included. Intergroup comparative analyses were carried out, the BRCA1 gene carriers subgroup was subjected to detailed analysis, and ROC curves were determined for the assessment of diagnostic usefulness of HE4 in ovarian and endometrial cancer. Results. Statistically lower serum HE4 and CA 125 levels were observed in BRCA1 gene mutation premenopausal carriers. Occult ovarian/fallopian tube cancer was found 3.6%. Each of those patients was characterized by slightly elevated levels of either CA 125 (63.9 and 39.4 U/mL) or HE4 (79 pmol/L). The ROC-AUC curves were 0.892 and 0.894 for diagnostic usefulness of ovarian cancer and 0.865 for differentiation of endometrial cancer from endometrial polyps. Conclusions. Patients with BRCA1 gene mutations have relatively low serum HE4 levels. Even the slightest elevation in HE4 or CA 125 levels in female BRCA1 carriers undergoing prophylactic surgery should significantly increase oncological alertness. The HE4 marker is valuable in ovarian and uterine cancer diagnosis.

Kassem L, Abdel-Rahman O
Targeting mTOR pathway in gynecological malignancies: Biological rationale and systematic review of published data.
Crit Rev Oncol Hematol. 2016; 108:1-12 [PubMed] Related Publications
BACKGROUND: mTOR inhibitors are widely used in different malignancies with several trials testing their efficacy and safety in gynecological malignancies. We aimed to review the current evidence that support the expansion of using such drugs in the treatment of advanced gynecological cancers.
METHODS: A comprehensive systematic review of literature has been conducted to include prospective trials that used everolimus, temsirolimus or ridaforolimus in the management of gynecological cancers and have available efficacy and toxicity results.
RESULTS: A total of 23 studies including 980 patients were considered eligible for our review. Our review included 16 phase II and 7 phase I studies with the majority of patients having uterine cancers. Regarding Endometrial cancer, the CBR ranged from 21% to 60% and median PFS from 2.8 months to 7.3 months. In Ovarian cancers, CBR ranged from 24% to 50% and median PFS from 3.2 months to 5.9 months. In the single phase II study in cervical cancer the CBR was 61% and median PFS was 3.5 months. The toxicity profile was consistent with what was observed previously in other malignancies with fatigue, mucositis, and hematological toxicities being the most common adverse events observed.
CONCLUSION: mTOR inhibitors seem to be a promising option in the second line management of advanced gynecological cancers with best safety and efficacy outcomes when given as a single agent or in combination with hormonal treatment. More research is needed for better patient selection.

Sehouli J, Tomè O, Dimitrova D, et al.
A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO).
J Cancer Res Clin Oncol. 2017; 143(3):541-550 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: In recurrent ovarian cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of recurrent ovarian cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC.
METHODS: Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m(2) d1 q4w or treosulfan p.o. 600 mg/m(2) d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life.
RESULTS: 250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred.
CONCLUSIONS: Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.

Janssen S, Bajrovic A, Schild SE, Rades D
A Scoring Instrument to Predict the Survival Prognoses of Patients with Metastatic Epidural Spinal Cord Compression from Gynecological Malignancies.
Anticancer Res. 2016; 36(10):5469-5472 [PubMed] Related Publications
AIM: To design a scoring instrument for rating overall survival (OS) of patients with metastatic epidural sinal cord compression (MESCC) from gynecological malignancies.
PATIENTS AND METHODS: In 22 patients treated with radiotherapy alone for MESCC from gynecological malignancies, ten factors were analyzed for effects on OS. Factors significantly associated with OS on multivariate analysis were included in a scoring instrument.
RESULTS: On multivariate analyses, no visceral metastases (p=0.004) and affection of 1-2 vertebrae (p=0.012) were significant. Scoring points for each factor were 0 or 1, depending on OS rates. After summing, scores of 0 (n=6), 1 (n=9) or 2 points (n=9) were obtained. OS rates were 0%, 78% and 100%, respectively, at 3 months and 0%, 33% and 86%, respectively, at 6 months (p<0.001).
CONCLUSION: An instrument was developed for estimating the lifespan of patients with MESCC from gynecological malignancies. This instrument can support physicians when picking an individual treatment.

Chantragawee C, Achariyapota V
Utilization of a Scored Patient-Generated Subjective Global Assessment in Detecting a Malnourished Status in Gynecologic Cancer Patients.
Asian Pac J Cancer Prev. 2016; 17(9):4401-4404 [PubMed] Related Publications
PURPOSE: To assess the prevalence of malnutrition in gynecologic cancer patients using the Scored Patient- Generated Subjective Global Assessment (PG-SGA) questionnaire.
MATERIALS AND METHODS: A total of 97 gynecologic cancer patients who never had any treatment but were planned for surgery were enrolled. The patients were asked to complete the scored PG-SGA form before the treatment was started. Attending physicians were also asked to complete other information in the PG-SGA form. Total scores were calculated and the patients were classified into 3 nutritional status levels.
RESULTS: Mean age was 54 years. Postoperative diagnoses were endometrial cancer in 42 cases (43.2%), ovarian cancer in 29 cases (29.9%), and cervical cancer in 26 cases (26.8%). Mean PG-SGA score was 5.2+4.7. Malnutrition (PG-SGA B and C) was found in 52 patients (53.6%, 95% CI 43.7% - 63.2%). Preoperative BMI, hemoglobin, serum albumin, and cancer stage were not significantly associated with nutritional status. Malnutrition was significantly more common among patients diagnosed with ovarian cancer, compared to other types of cancer (79.3% vs. 42.6%, p 0.004).
CONCLUSIONS: Prevalence of malnutrition among gynecologic cancer patients was 53.5%, according to the scored PG-SGA. Malnutrition was significantly more common among patients with ovarian cancer.

Woo JS, Apple SK, Sullivan PS, et al.
Systematic assessment of HER2/neu in gynecologic neoplasms, an institutional experience.
Diagn Pathol. 2016; 11(1):102 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: HER2/neu overexpression and/or amplification has been widely studied in a number of solid tumors, primarily in the breast. In gynecologic neoplasms, determination of HER2/neu status has not been well studied as a predictive biomarker in anti-HER2/neu treatment.
METHODS: We systematically evaluated the HER2/neu reactions by immunohistochemistry and fluorescent in situ hybridization in malignant gynecologic neoplasms as experienced in our institution.
RESULTS: The HER2/neu overexpression or amplification occurred in 8 % of the cancers of the gynecological organs in our series. Majority of the HER2/neu overexpression and/or amplification occurred in clear cell (27 %) and serous (11 %) carcinomas. HER2/neu positivity was also seen in undifferentiated as well as in mixed clear cell and serous carcinomas. Discordant IHC and FISH results (positive by FISH but not IHC) was seen in 2 cases. Majority of the HER2/neu overexpression and/or amplification occurs in the endometrium rather than the ovary. Heterogeneity of the HER2/neu by IHC staining was in < 2 % of the tumors in our series.
CONCLUSIONS: We recommend the HER2/neu studies on Müllerian carcinomas of clear cell, serous, and undifferentiated types, particularly when they arise in the endometrium. Since there are some discordant IHC/FISH results, we also propose performing the HER2/neu testing by FISH when the IHC score is less than 3 + .

Thiel FC, Parvanta P, Hein A, et al.
Chylous ascites after lymphadenectomy for gynecological malignancies.
J Surg Oncol. 2016; 114(5):613-618 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Chylous ascites, an accumulation of milky-white lymph fluid in the peritoneal cavity, is a rare complication following retroperitoneal lymphadenectomy. This study evaluated the appearance and management of chylous ascites following lymphadenectomy for gynecological malignancies.
METHODS: A total of 931 patients who underwent lymphadenectomy for gynecological malignancies at Erlangen University Hospital between 2002 and 2013 were reviewed retrospectively.
RESULTS: Chylous ascites occurred postoperatively in 28 of the 931 patients (3.0%). All patients with chylous ascites had undergone combined systematic para-aortic and pelvic lymphadenectomy (SAPL). Patients with chylous ascites had a larger mean number of lymph nodes removed (51.9 vs. 40.0, P = 0.002) and the proportion of laparoscopic SAPLs was significantly higher (20/28; 71.4%) in comparison with open surgery (8/28; 28.6%) (P < 0.0001). Additional parameters, such as the number of positive lymph nodes, were not significantly associated with the occurrence of chylous ascites. Conservative management was sufficient to resolve chylous ascites in all observed cases, with a mean time to resolution of 8 days.
CONCLUSIONS: Postoperative chylous ascites was more frequently observed in patients with laparoscopic SAPL in comparison with open SAPL and was strongly associated with a larger mean number of removed lymph nodes. J. Surg. Oncol. 2016;114:613-618. © 2016 Wiley Periodicals, Inc.

Toyoshima M, Tsuji K, Shigeta S, et al.
Leptomeningeal metastasis from gynecologic cancers diagnosed by brain MRI.
Clin Imaging. 2017 Jan - Feb; 41:42-47 [PubMed] Related Publications
Leptomeningeal metastasis (LM) is rarely observed in gynecologic cancers. As gadolinium-enhanced magnetic resonance imaging (Gd-MRI) is highly effective for diagnosing LM, the aim of this study is to describe the clinical behaviors and outcomes of LM patients who were diagnosed by Gd-MRI. After securing institutional review board approvals, we retrospectively reviewed patient records. Eight patients were found to have LM from gynecological malignancies. Primary tumors included three ovarian cancers, one tubal cancer, one peritoneal cancer, two endometrial cancers, and one cervical cancer. Gd-MRI of the brain and the spine is indicated as the high-priority inspection for the diagnosis of this devastating complication.

Jitkunnatumkul A, Tantipalakorn C, Charoenkwan K, Srisomboon J
Subsequent Oophorectomy and Ovarian Cancer after Hysterectomy for Benign Gynecologic Conditions at Chiang Mai University Hospital.
Asian Pac J Cancer Prev. 2016; 17(8):3845-8 [PubMed] Related Publications
This study was undertaken to determine the incidence of subsequent oophorectomy due to ovarian pathology or ovarian cancer in women with prior hysterectomy for benign gynecologic conditions at Chiang Mai University Hospital. Medical records of women who underwent hysterectomy for benign gynecologic diseases and pre-cancerous lesions between January 1, 2004 and December 31, 2013 at Chiang Mai University Hospital were retrospectively reviewed. The incidence and indications of oophorectomy following hysterectomy were analyzed. During the study period, 1,035 women had hysterectomy for benign gynecologic conditions. Of these, 590 women underwent hysterectomy with bilateral salpingo-oophorectomy and 445 hysterectomy with bilateral ovarian preservation or unilateral salpingo-oophorectomy. The median age was 47 years (range, 11-75 years). Ten women (2.45 %) had subsequent oophorectomy for benign ovarian cysts. No case of ovarian cancer was found. The mean time interval between hysterectomy and subsequent oophorectomy was 43.1 months (range, 2-97 months) and the mean follow-up time for this patient cohort was 51 months (range, 1.3-124.9 months). According to our hospital-based data, the incidence of subsequent oophorectomy in women with prior hysterectomy for benign gynecologic conditions is low and all present with benign conditions.

Oldan JD, Patel PS
Positron Emission Tomography/Computed Tomography for Gynecologic Malignancies.
Obstet Gynecol Surv. 2016; 71(9):545-56 [PubMed] Related Publications
IMPORTANCE: Positron emission tomography/Computed tomography(PET/CT) is widely used for gynecologic cancers.
OBJECTIVE: To determine when PET/CT should be used for gynecologic cancers.
EVIDENCE ACQUISITION: PubMed was reviewed for articles on PET/CT of all gynecologic cancers. National Comprehensive Cancer Network, Society of Gynecologic Oncology, and American College of Radiology guidelines were reviewed.
RESULTS: Whole-body PET/CT is useful for (1) initial staging of cervical and endometrial cancer, posttherapy assessment, radiation therapy planning, and posttreatment surveillance of cervical cancer, and (2) assessment of recurrence of cervical, endometrial, or ovarian cancer in the presence of symptoms. It is also useful for staging and recurrence of uterine sarcomas, and for staging of vulvar and vaginal cancer.
CONCLUSIONS: Positron emission tomography/Computed tomography is clinically valuable for a variety of gynecologic cancers.
RELEVANCE: PET/CT plays an important role in detection of initial disease and recurrence of gynecologic malignancies.

Dziggel L, Janssen S, Bajrovic A, et al.
Local Therapies Can Improve Intracerebral Control in Patients with Cerebral Metastasis from Gynecological Cancers.
Anticancer Res. 2016; 36(9):4777-80 [PubMed] Related Publications
BACKGROUND/AIM: Patients with gynecological malignancies account for 2% of patients with cerebral metastases. Many patients receive whole-brain irradiation (WBI) alone. Local therapies (resection, stereotactic radiosurgery (SRS)) are becoming more popular. This study compared intracerebral control after local therapy to WBI alone in patients with gynecological malignancies.
PATIENTS AND METHODS: Of 56 patients, 45 received WBI alone, 6 SRS alone and 5 resection plus WBI. Treatment type, age, performance score, cancer site, number of cerebral lesions, metastases outside the brain, recursive partitioning analysis (RPA) class and period from gynecological cancer diagnosis to brain metastasis treatment were evaluated.
RESULTS: On univariate analyses, local therapy (p=0.003), single cerebral lesion (p<0.001) and RPA class 1/2 (p=0.027) were positively related to intracerebral control. On Cox regression analysis, local therapy (p=0.013) and RPA class 1/2 (p=0.014) were significant.
CONCLUSION: Local therapies led to better intracerebral control than WBI alone and should be considered for brain metastasis from gynecological malignancies whenever reasonable.

Ponisio MR, Fowler KJ, Dehdashti F
The Emerging Role of PET/MR Imaging in Gynecologic Cancers.
PET Clin. 2016; 11(4):425-40 [PubMed] Related Publications
This article summarizes recent advances in PET/MR imaging in gynecologic cancers and the emerging clinical value of PET/MR imaging in the management of the 3 most common gynecologic malignancies: cervical, endometrial, and ovarian cancers. PET/MR imaging offers superior soft tissue contrast, improved assessment of primary tumor involvement because of high-resolution multiplanar reformats, and functional MR techniques such as diffusion-weighted MR imaging and dynamic contrast-enhanced MR imaging. This article discusses the challenges, future directions, and technical advances of PET/MR imaging, and the emerging new multimodality, multiparametric imaging techniques for integrating morphologic, functional, and molecular imaging data.

Schulte JJ, Lastra RR
Abdominopelvic washings in gynecologic pathology: A comprehensive review.
Diagn Cytopathol. 2016; 44(12):1039-1057 [PubMed] Related Publications
Abdominopelvic washings (APW) performed during gynecologic surgeries have become a common specimen evaluated by cytopathologists. Their role in staging of female genital tract tumors has changed significantly since they were first described, and continue to evolve. The ability of these washings to detect microscopic disease, even in the absence of gross disease, warrants the critical role that these washings play in the staging of certain female gynecologic tract tumors, allowing for optimal staging and subsequent treatment of the patient. Irrespective of the underlying pathology, the gamut of cytomorphologic findings that may be observed in APW is extensive, and ranges from benign lesions that may act as mimickers of malignancy, to both common and rare malignancies. This review discusses the changing role of APW in the staging of gynecologic tumors, and highlights the salient cytomorphologic features of these lesions, with emphasis in their correct identification, including cautionary notes to avoid over or misinterpretation. Diagn. Cytopathol. 2016;44:1039-1057. © 2016 Wiley Periodicals, Inc.

Lee SW, Yeo SG, Oh IH, et al.
Bone mineral density in women treated for various types of gynecological cancer.
Asia Pac J Clin Oncol. 2016; 12(4):e398-e404 [PubMed] Related Publications
AIM: Patients with gynecologic cancer frequently experience bone loss due to cancer treatments, including bilateral oophorectomy, chemotherapy and radiotherapy. This study evaluated treatment-associated changes in bone mineral density (BMD) in women with gynecologic cancer and compared changes among patients with different types of gynecologic cancer.
METHODS: BMD of the lumbar spine and femur was retrospectively analyzed using dual-energy X-ray absorptiometry in 118 women who underwent treatment for gynecological cancers and 132 women without gynecologic cancers. The cohort included 55 women with cervical cancer who underwent surgery followed by adjuvant chemotherapy and/or radiation therapy, 33 with endometrial cancer (EC) who underwent surgery followed by adjuvant radiation therapy and 30 with ovarian cancer who underwent bilateral oophorectomy followed by adjuvant platinum-based chemotherapy. Lumbar spine and femoral neck BMD were assessed at baseline and 12 months after treatment. Areal BMD, expressed as grams of mineral/cm(2) scanned, was compared with that in young healthy women (T-score).
RESULTS: Demographic characteristics and pretreatment BMDs, including T-scores, did not differ among cancer types. After adjustment for factors that can affect T-score, cancer type affected change in T-score 12 months after treatment. After adjustment for pretreatment age, parity, BMI and T-score, T-score 12 months after treatment was significantly lower in the EC than in the other groups.
CONCLUSIONS: Women treated for gynecological cancer, particularly those with EC who undergo bilateral oophorectomy followed by adjuvant radiation therapy or chemotherapy, should be managed in a timely manner to prevent or minimize bone loss.

Verma V, Simone CB, Wahl AO, et al.
Proton radiotherapy for gynecologic neoplasms.
Acta Oncol. 2016; 55(11):1257-1265 [PubMed] Related Publications
BACKGROUND: Proton beam therapy (PBT) is increasingly being used globally to treat a variety of malignancies. This is the first review assessing PBT for gynecologic neoplasms. Dose distribution to organs-at-risk (OARs), particularly bone marrow (BM), is addressed. Clinical outcomes and toxicity data are detailed.
MATERIAL AND METHODS: Systematic searches of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology were conducted for publications. There were no restrictions on publication dates. Sixteen original investigations were identified and analyzed for this review.
RESULTS: The available evidence for PBT in treating gynecologic cancers is of both low quantity and quality. The most studied scenarios for PBT include treatment of para-aortic lymph nodes, re-irradiation, and as an alternative to brachytherapy, and these also represent indications with the greatest opportunity for demonstrating as yet unproven toxicity reductions. Dosimetric studies have shown significantly decreased dose to OARs, such as the rectum, bladder, bowel, kidneys, BM, and femoral heads. This dose reduction to OARs with PBT is more pronounced within the low-dose volumes than the higher dose volumes, which radiobiologically could be expected to lower second malignancy rates. Clinical data, though no level 1 evidence, show appropriate stage-specific tumor control and outcomes with PBT treatment, along with low toxicity rates.
CONCLUSION: The existing data, albeit limited, warrant and can help guide larger scale and higher quality studies addressing whether PBT could provide clinically meaningful differences in toxicities and outcomes in women with gynecologic neoplasms.

Muallem MZ, Dimitrova D, Pietzner K, et al.
Implementation of Enhanced Recovery After Surgery (ERAS) Pathways in Gynecologic Oncology. A NOGGO-AGO* survey of 144 Gynecological Departments in Germany.
Anticancer Res. 2016; 36(8):4227-32 [PubMed] Related Publications
AIM: To gather standardized information of current perioperative management of gynecological oncology patients and to evaluate up to what extent the Enhanced Recovery after Surgery (ERAS) elements are established in the clinical routine of gynecologic oncology units in Germany.
MATERIALS AND METHODS: We performed a multi-centric nationwide survey among 654 primary, secondary and maximal health care gynecological departments in Germany. A multiple-choice questionnaire based on the principles of ERAS was developed to gather information about perioperative management of two fictional cases in gynecological oncology.
RESULTS: One hundred four units (22%) have been taken the survey. Only 49.5% of surveyed hospitals claimed to be adherent to more than 70% of ERAS elements in managing perioperative period of primary cytoreductive surgery in ovarian cancer patients. 21% of these hospitals implemented more than 80% and only 8.4% implemented more than 90%. The results in border-line tumors operations did not differ from those of ovarian cancer operations.
CONCLUSION: The implementation of ERAS elements in gynecologic oncology in Germany is still not satisfying as only half of the departments will now be able to apply 70% of these principles. Therefore, we plan the second step of this survey in order to be able to build a consistent structured reporting platform between gynecological oncology units in Germany to facilitate the wide implementation and standardization of ERAS protocol.

Capett MS, Vollú-Silva P, Melchiades VA, et al.
Characterization of Ciprofloxacin-Resistant and Ciprofloxacin-Susceptible Uropathogenic Escherichia coli Obtained from Patients with Gynecological Cancer.
Curr Microbiol. 2016; 73(5):624-32 [PubMed] Related Publications
The objective of this work was to assess the genetic characteristics of uropathogenic Escherichia coli, ciprofloxacin resistance or susceptibility, obtained from patients with gynecological cancer and urinary tract infection (UTI). Seventy-seven E. coli ciprofloxacin-resistant isolates and 38 ciprofloxacin-susceptible were analyzed by polymerase chain reaction (PCR) to determine the phylogenetic groups, virulence factors as iucC, fyuA, hlyC, cnf1 genes, and pks pathogenicity island. The presence of genes related to ciprofloxacin resistance such as qnrA, qnrB, qnrS, aac(6')-Ib-cr, and qepA, and the sequencing of DNA gyrase genes and topoisomerase IV were determined. The genetic profile of the isolates was determined by pulsed-field gel electrophoresis (PFGE). Statistical analysis was performed using Fisher's exact test and Chi-square test. Phylogenetic group B2 was the most prevalent although a great genetic diversity was observed by PFGE. Only genes associated to siderophores were found in ciprofloxacin-resistant isolates; however, in ciprofloxacin-susceptible isolates, genes related to siderophores and toxin, were detected. Additionally qnrB was detected in both populations, ciprofloxacin resistant and susceptible. DNA mutations in gyrA were Ser-83-Leu and Asp-87-Asn and in parC were Ser-80-Ile and Glu-84-Val, Glu-84-Lys. In conclusion, it was observed a high prevalence of qnrB in the population studied; in addition, it was the first time the pks island was observed only in ciprofloxacin-susceptible isolates.

Halaska MJ, Rob L, Robova H, Cerny M
Treatment of gynecological cancers diagnosed during pregnancy.
Future Oncol. 2016; 12(19):2265-75 [PubMed] Related Publications
Because of a notable increase in age at delivery, the incidence of malignancy diagnosed during pregnancy has substantially increased. This review aims to summarize the literature and expert knowledge on gynecologic cancers diagnosed in pregnancy regarding epidemiology, examination and staging procedures, description of treatment modalities and management of gynecological malignancies with special interest in cervical and ovarian cancer. Thorough attention is paid to the surgery and chemotherapy administration for early-stage cervical cancer diagnosed during pregnancy.

Gadducci A, Biglia N, Tana R, et al.
Metformin use and gynecological cancers: A novel treatment option emerging from drug repositioning.
Crit Rev Oncol Hematol. 2016; 105:73-83 [PubMed] Related Publications
Metformin exerts antitumor effects mainly through AMP-activated protein kinase [AMPK] activation and phosphatidylinositol 3-kinase [PI3K]-Akt-mammalian target of rapamycin [mTOR] inhibition. This drug leads to activation of the cellular energy-sensing liver kinase B1 [LKB1]/AMPK pathway. LKB1 is implicated as a tumor suppressor gene in molecular pathogenesis of different malignancies. AMPK is a serine/threonine protein kinase that acts as an ultra-sensitive cellular energy sensor maintaining the energy balance within the cell. AMPK activation inhibits mRNA translation and proliferation in cancer cells via down-regulation of PI3K/Akt/mTOR pathway. Moreover, metformin decreases the production of insulin, insulin-like growth factor, inflammatory cytokines and vascular endothelial growth factor, and therefore it exerts anti-mitotic, anti-inflammatory and anti-angiogenetic effects. Recent in vitro and experimental data suggest that metformin electively targets cancer stem cells, and acts together with chemotherapy to block tumor growth in different cancers. Several epidemiological studies and meta-analysis have shown that metformin use is associated with decreased cancer risk and/or reduced cancer mortality for different malignancies. The present review analyzes the recent biological and clinical data suggesting a possible growth-static effect of metformin also in gynecological cancers. The large majority of available clinical data on the anti-cancer potential of metformin are based on observational studies. Therefore long-term phase II-III clinical trials are strongly warranted to further investigate metformin activity in gynecological cancers.

Sun Y, Meng H, Jin Y, et al.
Serum lipid profile in gynecologic tumors: a retrospective clinical study of 1,550 patients.
Eur J Gynaecol Oncol. 2016; 37(3):348-52 [PubMed] Related Publications
BACKGROUND: The study was performed to characterize and compare the serum lipid profile in gynecologic cancers and benign diseases.
MATERIALS AND METHODS: A total of 1,550 age-matched females were included in this study: 760 patients with gynecologic cancers and 790 patients with benign diseases. Serum levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), total cholesterol (TC), and lipoprotein (a) were measured.
RESULTS: Compared to gynecologic benign disease group, gynecologic cancer group was associated with higher level of TG (p = 0.0002), as well as lower level of HDL-c (p < 0.0001), LDL-c (p = 0.004) and TC (p = 0.003). Compared to benign ovarian tumor group, ovarian cancer group had significantly lower levels of HDL-c (p < 0.0001), LDL-c (p = 0.0009), and TC (p < 0.0001), as well as a trend of higher level of lipoprotein (a) (p = 0.10). Compared to endometriosis group, endometrial cancer group showed higher levels of TG (p < 0.0001) and lower levels of HDL-c (p = 0.002). There was no significant difference in any lipid parameters between cervical cancer group and uterine leiomyomas group.
CONCLUSION: In conclusion, compared with benign diseases, gynecologic cancers are associated with a disordered lipid profile characterized by higher TG and lipoprotein (a) levels, and lower HDL-c, LDL-c, and TC levels. The association is most conspicuous in ovarian cancers. Endometrial cancer is accompanied by alterations only in TG and HDL-c levels, while cervical cancer does not appear to be associated with disordered lipid profile.

Park JW, Kim M
Replicating viruses for gynecologic cancer therapy.
Eur J Gynaecol Oncol. 2016; 37(3):295-304 [PubMed] Related Publications
Despite advanced therapeutic treatments, gynecologic malignancies such as cervical and ovarian cancers are still the top ten leading cause of cancer death among women in South Korea. Thus a novel and innovative approach is urgently needed. Naturally occurring viruses are live, replication-proficient viruses that specifically infect human cancer cells while sparing normal cell counterparts. Since the serendipitous discovery of the naturally oncotropic virus targeting gynecologic cancer in 1920s, various replicating viruses have shown various degrees of safety and efficacy in preclinical or clinical applications for gynecologic cancer therapy. Cellular oncogenes and tumor suppressor genes, which are frequently dysregulated in gynecologic malignancies, play an important role in determining viral oncotropism. Published articles describing replicating, oncolytic viruses for gynecologic cancers are thoroughly reviewed. This review outlines the discovery of replication-proficient virus strains for targeting gynecologic malignancies, recent progresses elucidating molecular connections between oncogene/tumor suppressor gene abnormalities and viral oncotropism, and the associated preclinical/clinical implications. The authors would also like to propose future directions in the utility of the replicating viruses for gynecologic cancer therapy.

Li Z, Zhang Z
The incidence and risk factors of venous thromboembolism following elective gynecological surgeries without systemic thromboprophylaxis--an observational cohort study in a Chinese tertiary hospital.
Clin Exp Obstet Gynecol. 2016; 43(3):365-9 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To investigate the incidence and risk factors of venous thromboembolism (VTE) after gynecological surgery without systemic thromboprophylaxis.
MATERIALS AND METHODS: Consecutive adult Chinese medical patients not receiving pharmacological or systemic mechanical prophylaxis for VTE before elective gynecological surgery. An observational cohort study of 620 patients in a gynecological department in a Chinese tertiary hospital.
RESULTS: Lower extremity deep venous thrombosis was detected by ultrasound examination in 57 (9.19%) of the patients, 39 had computed tomography pulmonary angiography (CTPA) evaluation after being diagnosed with lower extremity deep venous thrombosis (LEDVT), and the diagnosis was confirmed in 18 subjects, resulting in a pulmonary embolism (PE) incidence of 46.2% among the 39 patients, and 13 (72.2%) were asymptomatic and without significant clinical features.
CONCLUSIONS: In the absence of pharmacological or systemic mechanical prophylaxis, gynecological surgeries carried a significant risk for VTE in the Chinese study population. As clinical features are not able to reliably exclude the presence of PE, early routine prophylaxis is warranted based on risk factors in postoperative gynecological patients and should strongly be considered.

Meghelli L, Narducci F, Mariette C, et al.
Reporting adverse events in cancer surgery randomized trials: A systematic review of published trials in oesophago-gastric and gynecological cancer patients.
Crit Rev Oncol Hematol. 2016; 104:108-14 [PubMed] Related Publications
BACKGROUND: Few reports describe how adverse events (AEs) are reported in cancer surgery trials.
MATERIALS AND METHODS: We systematically reviewed 179 consecutive study reports issued between January 1, 1990 and November 15, 2014, which investigated surgery in oesophago-gastric (OG) or gynecologic (GY) cancer patients. Based on the reviewed reports, we assessed how AEs were reported according to CONSORT statement.
RESULTS: Morbidity assessment was the primary objective of 56 studies (31.3%). Postoperative AEs were described in 161 studies (90%). Definition of AEs and grading scale (NCI-CTC AE, Dindo-Clavien scale, etc …) were given in 27.3% and 16.8% of studies, respectively. AEs were reported by event and grade in 8.3% of studies. Definition of expectedness, seriousness, causality and safety population were present in 0.5%, 1.1%, 7.8%, and 7.2% of the studies, respectively. Reporting of AEs did not improve over time nor better in high-impact factor journals.
CONCLUSION: The reporting of AEs in cancer trials investigating surgery needs to be improved.

Sonni I, Iagaru A
PET Imaging Toward Individualized Management of Urologic and Gynecologic Malignancies.
PET Clin. 2016; 11(3):261-72 [PubMed] Related Publications
Advances in the understanding of cellular and molecular basis of tumor progression have spurred interest in the development of new targeted agents that are changing the therapeutic management of patients with cancer. In parallel to progression in the therapeutic area, new PET radiopharmaceuticals are being developed to guide the use of such targeted therapies. This article aims to give an overview on the role of PET imaging in the individualized management of patients affected by urologic and gynecologic malignancies, focusing on the most promising targets for therapies and for molecular imaging using PET.

Gutierrez F, Gonzalez-de-la-Fuente GA, Nazco GJ, et al.
Hematological toxicity of carboplatin for gynecological cancer according to body mass index.
Eur J Clin Pharmacol. 2016; 72(9):1083-9 [PubMed] Related Publications
PURPOSE: The aim of the present study was to analyze how patient weight affects the hematological toxicity of carboplatin and whether this toxicity is more prevalent in overweight patients.
METHODS: We performed a retrospective 2-year study of patients diagnosed with a gynecological cancer and whose treatment regimen contained carboplatin (AUC dose = 5 or 6) and paclitaxel (dose = 175 mg/m(2)) every 3 weeks (CP scheme). We recorded all severe hematological events (thrombocytopenia, neutropenia, and/or anemia grade III/IV) according to the CTCAE v4.03, as well as treatment modifications and the need for granulocyte colony-stimulating factors (G-CSF) and/or erythropoietin (EPO) or packed red blood cells (PRBC). Patients with a body mass index (BMI) ≥27 kg/m(2) were considered as overweight (OW) and those with a BMI <27 kg/m(2) were considered as normal weight (NW).
RESULTS: Fifty-two patients met the inclusion criteria (21 patients in the OW group, 31 patients in the NW group). The OW group showed a higher incidence of thrombocytopenia (95% confidence intervals (CI) 1.51-27.72; p < 0.02) and anemia (95% CI 1.06-33.63; p < 0.05). Moreover, this was reflected in a greater number of changes in the usual CP regimen (95% CI 2.19-44.32; p < 0.01). The need for G-CSF and/or EPO/PRBC was also significantly higher in the OW group (95% CI 1.08-12.16; p < 0.04).
CONCLUSIONS: Carboplatin dosing based on real weight in obese patients resulted in increased hematologic toxicity, mainly thrombocytopenia. Dose adjustment based on other descriptors of weight, such as adjusted weight, may be better tolerated by patients. However, future studies are needed to demonstrate not only better safety of carboplatin but also improved survival rates.

Van Le L, McCormack M
Enhancing Care of the Survivor of Gynecologic Cancer: Managing the Menopause and Radiation Toxicity.
Am Soc Clin Oncol Educ Book. 2016; 35:e270-5 [PubMed] Related Publications
It is expected that there will be 290,000 cases of gynecologic cancers in 2016. Of these cancers, 60,000 will be endometrial and 22,000 will be ovarian-the two most common gynecologic cancers. Endometrial and ovarian cancers occur in menopausal women with mean ages of 60 and 63, respectively. The majority of endometrial cancers are early stage, and 5-year survival is considered good at upwards of 75%. For ovarian cancer, while survival rates have improved, the 5-year survival rate for the most common stage (stage III) is 40%. Thus, a substantial number of patients with gynecologic cancer are menopausal, and a significant number of patients are survivors, particularly of endometrial cancers. It will be important for survivors of gynecologic cancers to receive care tailored to their needs as women and to mitigate gender-specific side effects of their cancer treatment.

Kristeleit RS, Miller RE, Kohn EC
Gynecologic Cancers: Emerging Novel Strategies for Targeting DNA Repair Deficiency.
Am Soc Clin Oncol Educ Book. 2016; 35:e259-68 [PubMed] Related Publications
The presence of a BRCA mutation, somatic or germline, is now established as a standard of care for selecting patients with ovarian cancer for treatment with a PARP inhibitor. During the clinical development of the PARP inhibitor class of agents, a subset of women without BRCA mutations were shown to respond to these drugs (termed "BRCAness"). It was hypothesized that other genetic abnormalities causing a homologous recombinant deficiency (HRD) were sensitizing the BRCA wild-type cancers to PARP inhibition. The molecular basis for these other causes of HRD are being defined. They include individual gene defects (e.g., RAD51 mutation, CHEK2 mutation), homozygous somatic loss, and whole genome properties such as genomic scarring. Testing this knowledge is possible when selecting patients to receive molecular therapy targeting DNA repair, not only for patients with ovarian cancer but also endometrial and cervical cancers. The validity of HRD assays and multiple gene sequencing panels to select a broader population of patients for treatment with PARP inhibitor therapy is under evaluation. Other non-HRD targets for exploiting DNA repair defects in gynecologic cancers include mismatch repair (MMR), checkpoint signaling, and nonhomologous end-joining (NHEJ) DNA repair. This article describes recent evidence supporting strategies in addition to BRCA mutation for selecting patients for treatment with PARP inhibitor therapy. Additionally, the challenges and opportunities of exploiting DNA repair pathways other than homologous recombination for molecular therapy in gynecologic cancers is discussed.

Balasubramaniam K, Ravn P, Christensen RD, et al.
Gynecological cancer alarm symptoms: is contact with specialist care associated with lifestyle and socioeconomic status? A population-based study.
Acta Obstet Gynecol Scand. 2016; 95(9):976-83 [PubMed] Related Publications
INTRODUCTION: The aim of this study was to determine the proportion of patients who were referred to specialist care after reporting gynecological cancer alarm symptoms to their general practitioner. We sought to investigate whether contact with specialist care was associated with lifestyle factors or socioeconomic status.
MATERIAL AND METHODS: Nationwide population-based prospective cohort study in Denmark, based on a random sample of 51 090 women aged 20 years or older from the general population. A web-based questionnaire regarding gynecological alarm symptoms and lifestyle was distributed to the invited individuals. Data about contact with specialist care were obtained from the National Patient Register and the National Health Insurance Service Registry, whereas information about socioeconomic status was collected from Statistics Denmark. Main outcome measures were percentages of patients having contact with specialist care and odds ratios (ORs) for associations between specialist care contact, lifestyle factors and socioeconomic status.
RESULTS: The study included 25 866 nonpregnant women; 2957 reported the onset of at least one gynecological cancer alarm symptom, and 683 of these (23.1%) reported symptoms to their general practitioner. The proportion of individuals having contact with specialist care ranged from 39.3% (pain during intercourse) to 47.8% (bleeding during intercourse). Individuals with higher educational level had significantly higher odds of contact with a specialist (OR 1.86, 95% CI 1.17-2.95).
CONCLUSIONS: Educational level influences contact with specialist care among patients with gynecological cancer alarm symptoms. Future studies should investigate inequalities in access to the secondary healthcare system.

Peres AL, Paz E Silva KM, de Araújo RF, et al.
Immunocytochemical study of TOP2A and Ki-67 in cervical smears from women under routine gynecological care.
J Biomed Sci. 2016; 23(1):42 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cervical cancer is one of the most common female cancers and is caused by human papillomavirus (HPV). Viral infection leads to cell cycle deregulation by inactivating p53 and retinoblastoma protein by viral oncoproteins E6 and E7, respectively. Then, nuclear proteins such as DNA topoisomerase type IIa (TOP2A) and Ki-67 show increased expression because of increased cell division. These molecules are used as biomarkers for immunohistochemistry analysis of cervical tissue.
METHODS: In this cross-sectional study, we recruited 110 women receiving regular gynecological surveillance at public health centers in Olinda - PE, Brazil. Cervicovaginal cells were collected to determine the presence of cytological abnormalities and HPV infection. Pap smear slides were used to evaluate the expression of TOP2A and Ki-67 using immunocytochemistry techniques.
RESULTS: Of the 110 women, 75.4 % showed HPV-DNA(+) infection (83/110) and 29.1 % showed cellular abnormalities (32/110). Two atypical cells of undetermined significance, one low-grade squamous intraepithelial lesion, and one high-grade squamous intraepithelial lesion samples showed no HPV-DNA. TOP2A was positive in 71.9 % of samples, while Ki-67 was positive in 81.2 %. Immunocytochemistry results were positive in 4 of 5 atypical cells of undetermined significance samples. In HPV-DNA(+) samples with cytological abnormalities, immunocytochemistry results were positive 96.4 % of samples (p < 0.0001; odds ratio = 28.0). Among the samples infected with HR-HPV, TOP2A(+) was effective in 71 % samples, while and Ki-67(+) was 77.4 %. Ki-67 and TOP2A were positive for all samples infected with HPV6, HPV11, and HPV18. Ki-67 was also positive for all HPV16 samples, except for one negative sample in cytopathology analysis.
CONCLUSIONS: TOP2A and Ki-67 antibodies may be used in combination for cervical cancer screening in immunocytochemistry assays.

Lind H, Alevronta E, Steineck G, et al.
Defecation into clothing without forewarning and mean radiation dose to bowel and anal-sphincter among gynecological cancer survivors.
Acta Oncol. 2016; 55(11):1285-1293 [PubMed] Related Publications
BACKGROUND: To analyze the relationship between mean radiation dose to the bowels and the anal-sphincter and occurrence of 'defecation into clothing without forewarning', a specific and serious fecal incontinence symptom after gynecological radiotherapy. Additional potential risk factors associated with the symptom are explored.
MATERIAL AND METHODS: Data were collected for 519 eligible gynecological cancer survivors, treated with pelvic radiotherapy, with a median follow-up of 5.8 years, using a study-specific questionnaire and medical records. Correlations between defecation into clothing without forewarning and mean dose to organs at risk; the anal-sphincter region, the rectum, the sigmoid and the small intestines were investigated, also taking other risk factors into account.
RESULTS: Twelve percent reported having had the symptom at least once in the preceding six months. Mean doses >50 Gy to the anal-sphincter region, the rectum, the sigmoid and the small intestines were related to the occurrence of the symptom. Significantly associated risk factors were deliveries with high birth weight, heart failure and lactose and/or gluten intolerance. After adjusting for these factors, mean doses >50 Gy to the anal-sphincter region, the sigmoid and the small intestines remained related to the occurrence of the symptom.
CONCLUSION: Mean doses to the bowels and anal-sphincter region are related to the risk of defecation into clothing without forewarning in long-term gynecological cancer survivors treated with pelvic radiotherapy. Further radiobiological modeling may distinguish which organ(s) contribute most to development of the symptom.

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