Treatment Of Gynecologic Cancers Research Articles

The Role of Galectins in Tumor Progression, Treatment and Prognosis of Gynecological Cancers.

Galectins are the member of soluble proteins that bind with β-galactoside containing glycans. These proteins have been considered to be associated in various important events such as different types of cancers. It has been found that galectins could contribute to neoplastic transformation or regulate cell growth, cell apoptosis, and immune cells, causing tumor invasion, progression, metastasis and angiogenesis. Somehow, galectins are also found to exert a protective effect on cancer in a tissue-dependent way. These glycans binding proteins have been shown to be involved in the regulation of different tumor suppressor genes and oncogenes with their possible roles in human cancers. Objective of the current review is to summarize the role of galectin-1, -3 -7, and -9 in tumorigenesis of gynecological cancers. Galectin protein may be a potential therapeutic target in gynecological malignancies due to reported radio- and chemo- sensitivities, immunotherapeutic, anti-angiogenic and anti-proliferative activities. This review considers the evidence for the future research that how galectins may be important in the progression and treatment of gynecological cancers along with its potent use as a novel prognostic marker.

Proceedings From the 1st International Conference 'Current Concepts and Controversies in Gynecologic and Urologic Oncology'.

The N.N. Alexandrov National Cancer Center of Belarus organized a collaborative international conference entitled 'Current Concepts and Controversies in Gynecologic and Urologic Oncology' with the International Gynecologic Cancer Society and the United States National Cancer Institute. International, regional, and national experts presented recent developments and local conditions in the treatment of gynecologic cancers. Findings were reviewed with the intent of optimizing the management of women with gynecologic cancers across the Commonwealth of Independent States region. At the end of the conference, a resolution was adopted to identify areas for improvement and future collaborations.

Development of Lower Extremity Lymphedema Nursing Practice Protocol for Patients Following Gynecologic Cancer Treatment

Development of Lower Extremity Lymphedema Nursing Practice Protocol for Patients Following Gynecologic Cancer Treatment

Survivorship in Women Undergoing Gynecological and Breast Cancer Treatment in Upper Egypt: The Impact of Quality of Life Improvement Educational Program

Survivorship in Women Undergoing Gynecological and Breast Cancer Treatment in Upper Egypt: The Impact of Quality of Life Improvement Educational Program

Practice guidelines for management of ovarian cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement.

Since after 2006 when the first edition of practice guidelines for gynecologic oncologic cancer treatment was released, the Korean Society of Gynecologic Oncology (KSGO) has published the following editions on a regular basis to suggest the best possible standard care considering updated scientific evidence as well as medical environment including insurance coverage. The Guidelines Revision Committee was summoned to revise the second edition of KSGO practice guidelines, which was published in July 2010, and develop the third edition. The current guidelines cover strategies for diagnosis and treatment of primary and recurrent ovarian cancer. In this edition, we introduced an advanced format based on evidence-based medicine, collecting up-to-date data mainly from MEDLINE, EMBASE, and Cochrane Library CENTRAL, and conducting a meta-analysis with systematic review. Eight key questions were raised by the committee members. For every key question, recommendations were developed by the consensus meetings and provided with evidence level and strength of the recommendation.

Correction to: Curcumin in Advancing Treatment for Gynecological Cancers with Developed Drug- and Radiotherapy-Associated Resistance.

The affiliation of the 6th author Dr. Abolfazl Mehdizadehkashi was incorrect. It has been corrected to Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran.

Curcumin in Advancing Treatment for Gynecological Cancers with Developed Drug- and Radiotherapy-Associated Resistance.

The development of resistance toward current cancer therapy modalities is an ongoing challenge in gynecological cancers, especially ovarian and cervical malignancies that require further investigations in the context of drug- and irradiation-induced resistance. In this regard, curcumin has demonstrated beneficial and highly pleiotropic actions and increased the therapeutic efficiency of radiochemotherapy. The antiproliferative, anti-metastatic, anti-angiogenic, and anti-inflammatory effects of curcumin have been extensively reported in the literature, and it could also act as a chemopreventive agent which mitigates the out-of-target harmful impact of chemotherapeutics on surrounding normal tissues. The current review discussed the modulating influences of curcumin on some cell and molecular features, including the cell signaling and molecular pathways altered upon curcumin treatment, the expression of target genes involved in the progression of gynecological cancers, as well as the expression of genes accountable for the development of resistance toward common chemotherapeutics and radiotherapy. The cell molecular targets implicated in curcumin's resensitizing effect, when used together with cisplatin, paclitaxel, and irradiation in gynecological cancers, are also addressed. Finally, rational approaches for improving the therapeutic benefits of curcumin, including curcumin derivatives with enhanced therapeutic efficacy, using nanoformulations to advance curcumin stability in physiological media and improve bioavailability have been elucidated.

Sperm-Hybrid Micromotor for Targeted Drug Delivery.

A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract. This system is demonstrated to be an efficient drug delivery vehicle by first loading a motile sperm cell with an anticancer drug (doxorubicin hydrochloride),guiding it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the sperm cell to deliver the drug locally. The sperm release mechanism is designed to liberate the sperm when the biohybrid micromotor hits the tumor walls,allowing it to swim into the tumor and deliver the drugthrough the sperm-cancer cell membrane fusion. In our experiments, the sperm cells exhibited a high drug encapsulation capability and drug carrying stability, conveniently minimizing toxic side effects and unwanted drug accumulation in healthy tissues. Overall, sperm cells are excellent candidates to operate in physiological environments, as they neither express pathogenic proteins nor proliferate to form undesirable colonies, unlike other cells or microorganisms. This sperm-hybrid micromotor is a biocompatible platform with potential application in gynecological healthcare, treating or detecting cancer or other diseases in the female reproductive system.

Radiation-induced angiosarcoma of the omentum diagnosed by laparoscopy: A case report.

Angiosarcoma is a rare malignant tumor with an aggressive clinical course and a poor prognosis. Intraperitoneal angiosarcoma, especially originating from the omentum, is extremely rare. We report a case of radiation-induced angiosarcoma of the omentum that arose in a 38-year-old female seven years after concurrent chemoradiotherapy for cervical cancer. The primary tumor was unknown until diagnostic laparoscopy revealed an unresectable omental mass. Pathological examination revealed high-grade malignant cells positive for endothelial markers. Although the small number of cases limits the consensus on optimal therapy for advanced angiosarcoma, the patient was managed successfully by taxane-based chemotherapy, leading to complete response and consequent complete cytoreductive surgery. Our report is the fifth case of radiation-induced angiosarcoma of the omentum, and all have developed after treatment for gynecologic cancer. Although very rare, this complication should be considered after radiation therapy in cancer treatment, particularly given the increasing importance of this therapy.

Management of Menopausal Symptoms in Women With Gynecologic Cancers

(Abstracted from Gynecol Oncol 2017;146:427–435) Treatment of gynecologic cancers usually involves surgery, systemic chemotherapy, and/or radiation therapy, which often result in loss of ovarian function. Many of these women will be cured or become long-term cancer survivors and will become postmenopausal.

Characteristics of the Prevention and Treatment of Gynecological Cancer in Japan

Characteristics of the Prevention and Treatment of Gynecological Cancer in Japan

Who Prescribes Hormone Replacement Therapy for Young Women With Radiation-Induced Premature Ovarian Failure?

One of the major consequences of treatment of gynecologic and gastrointestinal cancers with pelvic RT in young women is premature ovarian failure (PMOF). Hormone replacement therapy (HRT) can relieve menopausal symptoms and prevent long-term complications of early estrogen deficiency; however, its use is controversial. The purpose of this study is to evaluate practice patterns regarding PMOF and potential use of HRT among radiation oncologists (RO) treating women with pelvic RT. 2452 surveys were emailed to ASTRO members who specified their occupation as RO with a specialty in gynecological malignancies. The survey consisted of 17 questions focusing on responders’ practice patterns regarding pelvic RT and HRT, as well as demographic factors, practice scope and residency training. Data was analyzed using SPSS. A total of 237 respondents (10%) completed the survey, 64.5% men and 35.5% women. Mean age was 49 and mean number of years in practice was 17. 29.5% indicated practicing in an academic setting, 43.9% private practice and 80% identified as Caucasian. When asked whether respondents offer HRT when appropriate in patients undergoing pelvic RT, 58.8% of respondents indicated almost never, while 41.2% indicated either occasionally (<50%), frequently (>50%), or almost always (>90%). Younger age and fewer years in practice both significantly decreased recommendation for offering HRT (p=0.001), while age and years in practice did not have a significant relationship with how often a RO considered checking menopause status. Males were 2.79 times more likely to report almost never considering offering HRT than females. RO in private practice were 2.24 times more likely to report almost never considering offering HRT than those who did not indicate private practice. Of RO who reported that they do not prescribe HRT (n=152, 65.8% of sample), a total of 82.9% reported they referred patients for HRT management (p=0.006). RO most often indicated patient perceived barriers to receiving HRT included risk of developing breast cancer (73%), blood clot (63.7%), uterine cancer (45.1%). Half of RO indicated between 3 and 7 patient perceived barriers to HRT. There was no significant relationship with receiving training from RO specializing in gynecologic oncology and how often RO consider checking menopausal status or offering HRT. HRT in women affected by PMOF can relieve menopausal symptoms and prevent long-term complications of early estrogen deficiency. Though PMOF is a well-known consequence of RT for the treatment of pelvic malignancies, use of HRT is controversial due to potential serious complications and lack of published evidence based guidelines. Further investigation is critical to elucidate gender, age, practice setting, and numerous other disparities in considering HRT when appropriate.

Randomized, Controlled Trial of Dexamethasone Versus Dexamethasone Plus Hydrocortisone as Prophylaxis for Hypersensitivity Reactions Due to Paclitaxel Treatment for Gynecologic Cancer.

The aim of this study was to assess intravenous hydrocortisone (HCT) added to standard dexamethasone (DXM) prophylaxis for paclitaxel-associated hypersensitivity reactions (HSRs). Paclitaxel naives scheduled for 6 cycles of paclitaxel (plus platinum) were randomized to DXM alone (20 mg intravenously [IV]) versus DXM plus HCT (100 mg IV) as premedication including chlorpheniramine (10 mg IV), diphenhydramine (25 mg orally), and ranitidine (50 mg IV) 30 minutes before infusion. Clinic nurses observed for HSRs. Groups were well balanced for cancer type, stage, drug allergy, chemotherapy naivete, mean age, body mass index, and paclitaxel dose. The 44 DXM controls underwent 213 cycles and the 42 investigational DXM plus HCT group 192 per protocol cycles. Hypersensitivity reactions were observed among 9 (4.2%) DXM only cycles compared with 1 (0.5%) among DXM plus HCT cycles (P = 0.022). Hypersensitivity reactions occurred in 8 (18%) DXM only patients and in 1 (2.4%) among those correctly receiving DXM plus HCT (P = 0.030). All HSRs occurred in cycles 1 to 3, within 10 to 40 minutes after infusion initiation, and peaked in cycle 2 (5/39) for DXM recipients and in cycle 3 (1/30) for DXM plus HCT. Hypersensitivity reaction severity was grade 1 in 3 DXM only recipients and grade 2 in 6 DXM and 1 DXM plus HCT. A sole grade 3 HSR was in an intention-to-treat DXM-HCT patient, who erroneously received no HCT. Hypersensitivity reaction symptoms were facial flushing (8 episodes), dyspnea (7), palmar rash (1), and transient hypotension (1). Paclitaxel infusion was suspended for treatment of HSRs; in all cases, symptoms mitigated and infusion successfully restarted for the remaining dose. Adding HCT to routine DXM prophylaxis significantly decreased paclitaxel HSR frequency.

Inhibition of coiled coil domain containing protein 69 enhances platinum-induced apoptosis in ovarian cancer cells.

Cisplatin is a platinum-based drug that is used for the treatment of human gynecological cancers. However, molecular mechanisms of chemo-resistance in ovarian cancer are poorly understood. The aim of the study is to examine the role of coiled coil domain containing protein 69 (CCDC69) in the underlying mechanism of chemoresistance. Heavy CpG methylation (73.1% and 74.3%) was found in A2780 and A2780cis cells assessing by bisulfite sequencing. Restoration in the expression of CCDC69 was found in A2780 and A2780cis cells after 5-Aza-dC treatment. In fact, the expression levels of CCDC69 were about 3-4 fold higher in cisplatin-resistant A2780cis cells than its parental cisplatin-sensitive A2780 cells. When knockout CCDC69 in cisplatin-resistant A2780cis and SKOV3 cells by CRISPR/Cas9, the CCDC69 knockout cisplatin-resistant A2780cis and CCDC69 knockout SKOV3 cells were also shown increased sensitive to cisplatin treatment. Moreover, treating CCDC69 knockout A2780cis cells with cisplatin, abrogated G1 and G2/M arrest, increased of cleaved caspase 3&8, greater ΔΨm loss and higher levels of Bax were observed. When restoring CCDC69 expression in CCDC69 knockout A2780cis cells by transient transfection, it attenuated sensitivity to cisplatin. By immunoblotting, we found that depletion of CCDC69 increased p53 acetylation at K382 site and Bax mitochondrial redistribution. Additionally, inhibition of c-Myc enhanced cisplatin sensitivities in CCDC69 knockout A2780cis cells, overexpression of c-Myc reduced apoptosis in CCDC69 knockout SKOV3 cells. Our results showed that CCDC69 inhibition might interfere with the effectiveness of combination therapy with platinum drugs.

A national, prospective observational study of first recurrence after primary treatment for gynecological cancer in Norway

Gynecological cancer patients are routinely followed up for five years after primary treatment. However, the value of such follow up has been debated, as retrospective studies indicate that first recurrence is often symptomatic and occurs within two to three years of primary treatment. We prospectively investigated time to first recurrence, symptoms at recurrence, diagnostic procedures, and recurrence treatment in gynecological cancer patients after primary curative treatment. Clinicians from 21 hospitals in Norway interviewed 680 patients with first recurrence of gynecological cancer (409 ovarian, 213 uterine, and 58 cervical cancer patients) between 2012 and 2016. A standardized questionnaire was used to collect information on self-reported and clinical variables. Within two years of primary treatment, 72% of ovarian, 64% of uterine, and 66% of cervical cancer patients were diagnosed with first recurrence, and 54, 67, and 72%, respectively, had symptomatic recurrence. Of symptomatic patients, 25-50% failed to make an appointment before their next scheduled follow-up visit. Computer tomography was the most common diagnostic procedure (89% of ovarian, 76% of uterine, and 62% of cervical cancer patients), and recurrence treatment in terms of chemotherapy was most frequently planned (86% of ovarian, 46% of uterine, and 62% of cervical cancer patients). A majority of patients experienced symptomatic recurrence, but many patients failed to make an appointment earlier than scheduled. Most first recurrences occurred within two years of primary treatment; the mean annual incidence rate for years 3-5 after primary treatment was <7%. New models for follow up of gynecological cancer patients could be considered.

Risk factors for lower extremity lymphedema following treatment of gynecologic cancers: a meta-analysis

Objective To investigate the multiple risk factors for lower extremity lymphedema in patients following treatment of common gynecologic cancers by meta-analysis for systematic analysis and comprehensive quantitative study. Methods Clinical trials published up until August 2016 were retrieved from PubMed, Embase, and the Cochrane Library. The quality of the included studies was assessed by the Newcastle-Ottawa Scale, and data analysis was performed using Stata 14.0 and RevMan 5.3. The strength of the associations between risk factors and gynecologic cancer-related lower extremity lymphedema was described as odds ratio (OR) and 95% confidence intervals (CI). Results Eighteen studies were included in the meta-analysis, and 8 relevant factors were identified. The risk factors for lower extremity lymphedema after treatment of gynecologic cancer mainly included radiotherapy (OR=2.45, 95%CI: 2.05-2.95, P=0.000), FIGO stage (OR=2.29, 95%CI: 1.66-3.14, P=0.000), and pelvic lymph node dissection (OR=2.00, 95%CI: 1.02-3.91, P=0.040). Conclusions Radiotherapy, FIGO stage, and pelvic lymph node dissection are the main risk factors for lower extremity lymphedema after treatment of gynecologic cancers. Key words: Gynaecological neoplasms; Lower extremity lymphedema; Risk factors

OC14.04: Role of intraoperative ultrasound to extend minimally invasive surgery for treatment of recurrent gynecological cancer

OC14.04: Role of intraoperative ultrasound to extend minimally invasive surgery for treatment of recurrent gynecological cancer

Nurses' perceptions of providing psychosexual care for women experiencing gynaecological cancer.

To gain insight into how Western Australian nurses conceptualise the provision of psychosexual care for women undergoing gynaecological cancer treatment and how this aligns with nurses globally. A qualitative descriptive design was chosen to facilitate insight into nurses' perspectives of their reality. Seventeen nurses working at a tertiary women's hospital in Western Australia participated in one-on-one interviews and were asked to describe their perceptions and identify factors that facilitate or challenge psychosexual care provision. Data analysis revealed five themes affecting the provision of psychosexual care: (1) Nurses use strategies to aid the conversation (subthemes: supporting the woman, facilitating engagement); (2) Women have unique psychosexual needs (subthemes: diversity, receptiveness); (3) Nurses are influenced by personal and professional experience and values (subthemes: confidence, values, making assumptions); (4) Systems within the health service affect care (subthemes: being supported by the system, working as a team); and (5) Society influences attitudes around sexuality. Nurses' views differed around whether these factors had a positive or negative impact on the conversation required to provide this care. Factors influencing nurses' provision of psychosexual care are multifaceted and differ amongst nurses. Recommended strategies to improve service provision include guidelines and documentation to integrate assessment of psychosexual issues as standard care, encouraging shared responsibility of psychosexual care amongst the multidisciplinary team and implementing education programs focussed on improving nurses' confidence and communication skills.

Thiol-Michael ‘click’ hydrogels as an imageable packing material for cancer therapy

Gynecological cancer treatment strategies commonly employ pelvic brachytherapy, a technique that temporarily locates radioactive materials in or near the source of the tumor. Despite numerous advances in brachytherapy treatment protocols, advances in the required vaginal packing materials lag significantly. This paper describes a packing material for vaginal brachytherapy based on a poly(ethylene glycol) (PEG)-based hydrogel. Commercially available oligomeric starting materials rapidly formed a hydrogel upon action of mild base (NaHCO3) through a thiol-Michael addition reaction. Tuning the base concentration enabled rapid formation of hydrogels with moduli sufficient for effective tissue displacement (>10 kPa). The poly(ethylene glycol) diacrylate oligomer molecular weight exerted minimal influence on the hydrogel modulus. The hydrogels absorbed up to four times their weight in water from the dry state. CT imaging demonstrated distinguishability between hydrogel, water, and metal medical tools. The hydrogels did not induce significant IL-8 upregulation or cytotoxicity when cultured against vaginal macrophage cells, suggesting lack of immunogenicity. Our findings support these hydrogels as ideal candidates for a packing material in pelvic brachytherapy applications.

Lower Body Lymphedema in Patients with Gynecologic Cancer.

Lower body lymphedema is a chronic condition and a significant cause of morbidity following treatment of gynecologic cancer that strongly impacts patients' quality of life (QoL). Most studies on secondary lymphedema have been performed on the upper limb after breast cancer treatment and much less is known about lower body lymphedema after gynecologic malignancies. This review focuses on secondary lymphedema due to gynecologic cancer treatment, analyzing its incidence in the different types of gynecologic cancer, diagnosis, risk factors, impact on QoL and treatment. A systematic search of Medline has been performed to track the studies evaluating lower body lymphedema after treatment for endometrial, ovarian, cervical and vulvar cancer. Unfortunately, there is no consensus about a uniform evaluation and, as a consequence, the reported incidence is broadly different among the studies. Standardization in lymphedema evaluation is required to better compare the outcome of different types of treatment.