Low serum creatinine levels are associated with major post-operative complications in patients undergoing surgery with gynecologic oncologists.

OBJECTIVE: Serum creatinine is a byproduct of muscle metabolism, and low creatinine is postulated to be associated with diminished muscle mass. This study examined the association between low pre-operative serum creatinine and post-operative outcomes. METHODS: This retrospective cohort study utilized the 2014-2021 National Surgical Quality Improvement Program to identify patients undergoing surgery with gynecologic oncologists. Patients with missing pre-operative creatinine, end-stage renal disease, sepsis, septic shock, dialysis, or pregnancy were excluded. Pre-operative creatinine was categorized into markedly low (≤0.44 mg/dL), mildly low (0.45-0.64 mg/dL), normal (0.65-0.84 mg/dL), and four categories of elevated levels (0.85-1.04, 1.05-1.24, 1.25-1.44, and ≥1.45 mg/dL). Outcomes included major (≥Grade 3) 30-day complications, categorized into any complications, wound, cardiovascular and pulmonary, renal, infectious, and thromboembolic complications. Also examined were 30-day readmissions, reoperations, and mortality. Logistic regressions assessed the association between creatinine and complications, with stratification by albumin and sensitivity analysis with propensity score matching. RESULTS: Among 84 786 patients, 0.8% had markedly low, 19.6% mildly low, and 50.2% normal creatinine; the remainder had elevated creatinine. As creatinine decreased, the risks of major complications increased in a dose-dependent manner on univariable and multivariable analyses. A total of 9.6% (n=63) markedly low patients experienced major complications, second to creatinine ≥1.45 mg/dL (9.9%, n=141). On multivariable models, both markedly and mildly low creatinine were associated with higher odds of major complications (OR 1.715, 95% CI 1.299 to 2.264 and OR 1.093, 95% CI 1.001 to 1.193) and infections (OR 1.575, 95% CI 1.118 to 2.218 and OR 1.165, 95% CI 1.048 to 1.296) versus normal. Markedly low creatinine had similar ORs to creatinine ≥1.45 mg/dL and was further associated with higher odds of cardiovascular and pulmonary complications (OR 2.301, 95% CI 1.300 to 4.071), readmissions (OR 1.403, 95% CI 1.045 to 1.884), and mortality (OR 2.718, 95% CI 1.050 to 7.031). After albumin stratification, associations persisted for markedly low creatinine. Propensity-weighted analyses demonstrated congruent findings. CONCLUSIONS: Low creatinine levels are associated with major post-operative complications in gynecologic oncology in a dose-dependent manner. Low creatinine can offer useful information for pre-operative risk stratification, surgical counseling, and peri-operative management.

Incorporating low haemoglobin into a risk prediction model for conversion in minimally invasive gynaecologic oncology surgeries.

BACKGROUND: A well-known complication of laparoscopic management of gynaecologic masses and cancers is the need to perform an intraoperative conversion to laparotomy. The purpose of this study was to identify novel patient risk factors for conversion from minimally invasive to open surgeries for gynaecologic oncology operations. METHODS: This was a retrospective cohort study of 1356 patients ≥18 years of age who underwent surgeries for gynaecologic masses or malignancies between February 2015 and May 2020 at a single academic medical centre. Multivariable logistic regression was used to study the effects of older age, higher body mass index (BMI), higher American Society of Anaesthesiologist (ASA) physical status, and lower preoperative haemoglobin (Hb) on odds of converting from minimally invasive to open surgery. Receiver operating characteristic (ROC) curve analysis assessed the discriminatory ability of a risk prediction model for conversion. RESULTS: A total of 704 planned minimally invasive surgeries were included with an overall conversion rate of 6.1% (43/704). Preoperative Hb was lowest for conversion cases, compared to minimally invasive and open cases (11.6 ± 1.9 vs 12.8 ± 1.5 vs 11.8 ± 1.9 g/dL, p<.001). Patients with preoperative Hb <10 g/dL had an adjusted odds ratio (OR) of 3.94 (CI: 1.65-9.41, p=.002) for conversion while patients with BMI ≥30 kg/m2 had an adjusted OR of 2.86 (CI: 1.50-5.46, p=.001) for conversion. ROC curve analysis using predictive variables of age >50 years, BMI ≥30 kg/m2, ASA physical status >2, and preoperative haemoglobin <10 g/dL resulted in an area under the ROC curve of 0.71. Patients with 2 or more risk factors were at highest risk of requiring an intraoperative conversion (12.0%). CONCLUSIONS: Lower preoperative haemoglobin is a novel risk factor for conversion from minimally invasive to open gynaecologic oncology surgeries and stratifying patients based on conversion risk may be helpful for preoperative planning.

Minimally invasive surgery for management of gynaecologic masses (masses that affect the female reproductive organs) is often preferred over more invasive surgery, because it involves smaller surgical incisions and can have overall better recovery time. However, one unwanted complication of minimally invasive surgery is the need to unexpectedly convert the surgery to an open surgery, which entails a larger incision and is a higher risk procedure. In our study, we aimed to find patient characteristics that are associated with higher risk of converting a minimally invasive surgery to an open surgery. Our study identified that lower levels of preoperative haemoglobin, the protein that carries oxygen within red blood cells, is correlated with higher risk for conversion. This new risk factor was used with other known risk factors, including having higher age, higher body mass index, and higher baseline medical complexity to create a model to help surgical teams identify high risk patients for conversion. This model may be useful for surgical planning before and during the operation to improve patient outcomes.

Direct oral anticoagulant use in gynecologic oncology: A Society of Gynecologic Oncology Clinical Practice Statement.

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in women with gynecologic malignancies. This practice statement provides clinical data and overall quality of evidence regarding the use of direct oral anticoagulants (DOACs) in this patient population. Specifically, it reviews patient selection, safety measures, and nuances of perioperative use of these medications. The scope of this document is limited to DOAC use in gynecologic oncology rather than a broad discussion of VTE prophylaxis and management in general. The following recommendations and examination of extant data are based on DOAC trials conducted primarily in mixed populations with different cancer subtypes. Many of these trials include few, or no, women with gynecologic cancer. However, because there is very limited data in gynecologic cancer-specific populations, the results of these studies represent the best available evidence to support treatment recommendations in our patients. The members of the Society of Gynecologic Oncology (SGO) Clinical Practice Committee believe that the results of these studies may be extrapolated, with caution, to VTE treatment and prophylaxis for patients with gynecologic cancer.

Inflammatory markers in gynecologic oncology patients hospitalized with COVID-19 infection.

OBJECTIVE: Elevated inflammatory markers are predictive of COVID-19 infection severity and mortality. It is unclear if these markers are associated with severe infection in patients with cancer due to underlying tumor related inflammation. We sought to further understand the inflammatory response related to COVID-19 infection in patients with gynecologic cancer. METHODS: Patients with a history of gynecologic cancer hospitalized for COVID-19 infection with available laboratory data were identified. Admission laboratory values and clinical outcomes were abstracted from electronic medical records. Severe infection was defined as infection requiring ICU admission, mechanical ventilation, or resulting in death. RESULTS: 86 patients with gynecologic cancer were hospitalized with COVID-19 infection with a median age of 68.5 years (interquartile range (IQR), 59.0-74.8). Of the 86 patients, 29 (33.7%) patients required ICU admission and 25 (29.1%) patients died of COVID-19 complications. Fifty (58.1%) patients had active cancer and 36 (41.9%) were in remission. Patients with severe infection had significantly higher ferritin (median 1163.0 vs 624.0 ng/mL, p < 0.01), procalcitonin (median 0.8 vs 0.2 ng/mL, p < 0.01), and C-reactive protein (median 142.0 vs 62.3 mg/L, p = 0.02) levels compared to those with moderate infection. White blood cell count, lactate, and creatinine were also associated with severe infection. D-dimer levels were not significantly associated with severe infection (p = 0.20). CONCLUSIONS: The inflammatory markers ferritin, procalcitonin, and CRP were associated with COVID-19 severity in gynecologic cancer patients and may be used as prognostic markers at the time of admission.

Risk factors for bloodstream infections in gynecological cancer.

OBJECTIVE: Infections are a threat to frail patients as they have a higher risk of developing serious complications from bloodstream pathogens. The aim of this study was to determine which factors can predict or diagnose bloodstream infections in patients with an underlying gynecologic malignancy. MATERIALS AND METHODS: Between July 2016 and December 2017, 68 patients visiting the emergency room with an underlying gynecologic malignancy were evaluated. Variables concerning underlying disease, invasive procedures, and laboratory and clinical parameters were analyzed. Patients were divided into three groups based on their blood and urine specimens (positive blood specimens, positive urine specimens, and no positive specimens; patients who had both positive blood and urine specimens were included in the group of positive blood specimens). Risk factors for surgical site infections, recent (<30 days) surgery, and chemotherapy were studied separately. RESULTS: 68 patients were included in the analysis. Mean age was 55.6 years (standard deviation 14.1). 44% of patients had ovarian cancer, 35% cervical cancer, 12% endometrial cancer, and 9% had other cancer types. In total, 96% of all patients had undergone surgery. Patients who had been treated with chemotherapy were at a higher risk of developing bloodstream infection (P=0.04; odds ratio (OR)=7.9). C reactive protein, bilirubin, and oxygen saturation (SO2) were significantly different between patients with an underlying infection and those who had none. Only C reactive protein maintained its significance in a linear model, with a cut-off of 180 mg/L (linear regression, P=0.03; OR=4). CONCLUSIONS: Chemotherapy is a risk factor for the development of bloodstream infections in patients with an underlying gynecologic malignancy; C reactive protein could be a useful tool in making this diagnosis.

Perioperative glycemic measures among non-fasting gynecologic oncology patients receiving carbohydrate loading in an enhanced recovery after surgery (ERAS) protocol.

INTRODUCTION: Preoperative carbohydrate loading is an effective method to control postoperative insulin resistance. However, data are limited concerning the effects of carbohydrate loading on preoperative hyperglycemia and possible impacts on complication rates. METHODS: A prospective cohort study was performed of patients enrolled in an enhanced recovery after surgery pathway at a single institution. All patients underwent laparotomy for known or suspected gynecologic malignancies. Patients who had been diagnosed with diabetes preoperatively and those prescribed total parenteral nutrition by their providers were excluded. Data regarding preoperative carbohydrate loading with a commercial maltodextrin beverage, preoperative glucose testing, postoperative day 1 glucose, insulin administration, and complications (all complications, infectious complications, and hyperglycemia-related complications) were collected. The primary endpoint of the study was the incidence of postoperative infectious complications, defined as superficial or deep wound infection, organ/space infection, urinary tract infection, pneumonia, sepsis, or septic shock. RESULTS: Of 415 patients, 76.9% had a preoperative glucose recorded. The mean age was 60.5±12.4 years (range 18-93). Of those with recorded glucose values, 30 patients (9.4%) had glucose ≥180 mg/dL, none of whom were actually given insulin preoperatively. Median preoperative glucose value was significantly increased after carbohydrate loading (122.0 mg/dL with carbohydrate loading vs 101.0 mg/dL without, U=3143, p=0.001); however, there was no relationship between carbohydrate loading and complications. There was a significantly increased risk of hyperglycemia-related complications with postoperative day 1 morning glucose values ≥140 mg/dL (OR 1.85, 95% CI 1.07 to 3.23; p=0.03). Otherwise, preoperative and postoperative hyperglycemia with glucose thresholds of ≥140 mg/dL or ≥180 mg/dL were not associated with increased risk of other types of complications. DISCUSSION: Carbohydrate loading is associated with increased preoperative glucose values; however, this is not likely to be clinically significant as it does not have an impact on complication rates. Preoperative hyperglycemia is not a risk factor for postoperative complications in a carbohydrate-loaded population when known diabetic patients are excluded. PRECIS: While glucose increased with carbohydrate loading in non-diabetic patients, this was not associated with complications.

Deep vein thrombosis and serum D-dimer after pelvic lymphadenectomy in gynecological cancer.

INTRODUCTION: Venous thromboembolism prevention during the perioperative period requires comprehensive risk-level assessment. The aim of this study was to evaluate the incidence of deep vein thrombosis and to assess the cut-off levels of serum D-dimer as a screening strategy for deep vein thrombosis during the perioperative period. METHODS: A total of 205 patients (ovarian cancer: 68, endometrial cancer: 76, cervical cancer: 61) who underwent gynecological surgery, including retroperitoneal lymph node dissection, were enrolled. We retrospectively analyzed the data on the cut-off value of D-dimer assessed using area under the receiver operating characteristic curve preoperatively, and 2 or 3 months, postoperatively. All patients underwent leg vein ultrasonography regardless of the serum D-dimer level. Furthermore, CT scans were performed to evaluate both disease status and venous thromboembolism, including pulmonary thromboembolism. Statistical analyzes were performed using the Mann-Whitney U-test (D-dimer values of each cancer), Chi-square test, Fisher's exact test (incidence of deep vein thrombosis), and one-way analysis of variance (patient characteristics). RESULTS: A total of 205 patients (ovarian cancer: 68, endometrial cancer: 76, cervical cancer: 61) who underwent gynecological surgery, including retroperitoneal lymph node dissection, were included in the analysis. Deep vein thrombosis rates were significantly higher in patients with ovarian cancer (P<0.001). The postoperative D-dimer value was significantly higher than the preoperative value. Postoperative D-dimer values were also significantly higher in patients who received adjuvant chemotherapy (P=0.001). The cut-off value of D-dimer was 1.55 µg/mL preoperatively (sensitivity, 48.0%; specificity, 94.1%), and this value was higher postoperatively, at 1.95 µg/mL (sensitivity, 37.0%; specificity, 90.9%). CONCLUSION: Postoperative D-dimer values are higher not only after surgery but also in patients who received adjuvant chemotherapy. The cut-off value of D-dimer at 2 or 3 months postoperatively was higher than preoperative value.

Predictive and prognostic values of preoperative platelet parameters in patients with gynecological tumors.

BACKGROUND: Platelets play a role in tumor cell growth, metastasis, and angiogenesis, and the present study aimed to evaluate diagnostic and prognostic values of platelet parameters in patients with gynecological tumors. METHODS: A total of 1062 women were included. Differences of platelet parameters (platelet count [PLT], plateletcrit [PCT], mean platelet volume [MPV], platelet-large cell rate [P-LCR], and platelet distribution width [PDW]) between different categories were analyzed by nonparametric test. The optimal cutoff value was calculated with receiver operating characteristic analysis. Overall survivals were analyzed with Kaplan-Meier method and log-rank tests for univariate analysis. RESULTS: Platelet count and PCT were significantly increased, and MPV and P-LCR were significantly reduced in malign and benign gynecological tumor groups compared with the controls (P < .001); PDW had no significant differences. There were no significant differences in PLT, PCT, MPV, P-LCR, and PDW between different tumor locations and pathologic types. The optimal cutoff values of PLT, PCT, MPV and P-LCR were 274, 0.26, 10.08, and 24.8 (AUC: 0.661, 0.643, 0.593, 0.562), and PCT had preferable sensibility and specificity (50.84% and 70.42%) in predicting the presence of gynecological tumors. According to survival analysis, increased PLT (≥274 × 109 /L) and PCT (≥0.26), and induced MPV (<10.08 fL) and P-LCR (<24.8%) were associated with shorter overall survival. CONCLUSIONS: Platelet count, PCT, MPV, and P-LCR can be used as preferable auxiliary parameters for predicting the presence of gynecological tumors. Increased PLT and PCT, or decreased MPV and P-LCR indicated a heavier tumor burden and shorter overall survival.

FeOOH@Metal-Organic Framework Core-Satellite Nanocomposites for the Serum Metabolic Fingerprinting of Gynecological Cancers.

High-throughput metabolic analysis is of significance in diagnostics, while tedious sample pretreatment has largely hindered its clinic application. Herein, we designed FeOOH@ZIF-8 composites with enhanced ionization efficiency and size-exclusion effect for laser desorption/ionization mass spectrometry (LDI-MS)-based metabolic diagnosis of gynecological cancers. The FeOOH@ZIF-8-assisted LDI-MS achieved rapid, sensitive, and selective metabolic fingerprints of the native serum without any enrichment or purification. Further analysis of extracted serum metabolic fingerprints successfully discriminated patients with gynecological cancers (GCs) from healthy controls and also differentiated three major subtypes of GCs. Given the low cost, high-throughput, and easy operation, our approach brings a new dimension to disease analysis and classification.

Application value of Caprini risk assessment model and elevated tumor-specific D-dimer level in predicting postoperative venous thromboembolism for patients undergoing surgery of gynecologic malignancies.

AIM: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in gynecologic malignant patients after surgery. We aimed to validate the Caprini risk assessment model (RAM) and elevated tumor-specific D-dimer as predictive marker of postoperative VTE for patients undergoing surgery of gynecologic malignancies. METHODS: Inpatients were divided into five groups (low: score = 0-1; moderate: score = 2; high: score = 3-4; higher: score = 5-7; sup-high: score > 7) and treated according to their risk level after the surgery during the hospitalization according to the Caprini RAM. D-dimer level was detected during the perioperative period. If D-dimer did not fall to normal reference range on the seventh day after operation, the use of low-molecular-weight heparin was prolonged to 28 days after surgery. RESULTS: The majority (853/974, 87.6%) of the patients was in the Caprini score ≥5, with an overall VTE incidence of 1.75%. The VTE group had significantly higher Caprini score, CA125, vascular invasion rate and lymph node metastasis rate. If 1.5 µg/mL was used as the D-dimer cut-off value to predicting VTE, the sensitivity was 87.5%, the specificity was 93.8% and the negative predictive value was 99.2%. The D-dimer level was a marker for prolonging the anticoagulants use during the perioperative period, especially for the sup-high group. CONCLUSION: The Caprini RAM is an effective and reliable VTE risk prediction tool for patients undergoing gynecological malignant tumor surgery. The group (score ≥ 5) can be divided into two subgroups (higher: score = 5-7 and sup-high: score > 7), which may better predict the occurrence of VTE for malignant tumor patients. Great than 1.5 µg/mL D-dimer before operation should be given more attention for the presence of VTE.

Goal-directed hemodynamic management in patients undergoing primary debulking gynaecological surgery: A matched-controlled precision medicine study.

BACKGROUND: Usefulness of intraoperative goal-directed hemodynamic management (GDHM) for patients without comorbidities is debated. After clinical implementation of a pulse contour analysis-guided GDHM protocol, which foresees early vasopressor use for recruiting unstressed volume, we conducted a matched-controlled analysis to explore its impact on the amount of fluids intraoperatively administered to patients without comorbidities who underwent extended abdominal surgery for ovarian cancer. METHODS: After 1:1 matching accounting for body mass index, oncologic disease severity and intraoperative blood losses, 22 patients treated according to this GDHM protocol were compared to a control group of 22 patients who had been managed according to the clinical decision of attending physicians, taken without advanced monitoring. Results are displayed as median[interquartile range]. RESULTS: All analyzed patients underwent radical hysterectomy, bilateral adnexectomy, bowel resection, peritonectomy and extended pelvic/periaortic lymphadenectomy; median length of surgery was 517[480-605] min in patients receiving GDHM and 507[480-600] min in control group. Intraoperatively, patients undergoing GDHM received less fluids (crystalloids 2950[2700-3300] vs. 5150[4700-6000] mL, p < 0.001; colloids 100[50-200] vs. 750[500-1000] mL, p < 0.001) and showed a trend to more frequent vasopressor administration (32 vs 9%, p = 0.13). Greater intraoperative diuresis (540[480-620] mL vs. 450[400-500] mL, p = 0.007), lower blood lactates at surgery end (1.5[1.1-2] vs. 4.1[3.3-5] mmol/L, p < 0.001), shorter time to bowel function recovery (1 [1, 2] vs. 4 [3-5] days, p < 0.001) and hospital discharge (7 [6-8] vs 12 [9-16] days, p < 0.0001) were detected in patients receiving GDHM. CONCLUSIONS: In high-tumor load gynaecological patients without comorbidities who receive radical and prolonged surgery, intraoperative use of this novel GDHM protocol helped limit fluids administration with safety.

Systemic and local effects of vaginal dehydroepiandrosterone (DHEA): NCCTG N10C1 (Alliance).

BACKGROUND: Dehydroepiandrosterone (DHEA) is helpful for treating vaginal symptoms. This secondary analysis evaluated the impact of vaginal DHEA on hormone concentrations, bone turnover, and vaginal cytology in women with a cancer history. METHODS: Postmenopausal women, diagnosed with breast or gynecologic cancer, were eligible if they reported at least moderate vaginal symptoms. Participants could be on tamoxifen or aromatase inhibitors (AIs). Women were randomized to 3.25 versus 6.5 mg/day of DHEA versus a plain moisturizer (PM) control. Sex steroid hormone levels, biomarkers of bone formation, vaginal pH, and maturation index were collected at baseline and 12 weeks. Analysis included independent t tests and Wilcoxon rank tests, comparing each DHEA arm with the control. RESULTS: Three hundred forty-five women contributed evaluable blood and 46 contributed evaluable cytology and pH values. Circulating DHEA-S and testosterone levels were significantly increased in those on vaginal DHEA in a dose-dependent manner compared to PM. Estradiol was significantly increased in those on 6.5 mg/day DHEA but not in those on 3.25 mg/day DHEA (p < 0.05 and p = 0.05, respectively), and not in those on AIs. Biomarkers of bone formation were unchanged in all arms. Maturation of vaginal cells was 100% (3.25 mg/day), 86% (6.5 mg/day), and 64% (PM); pH decreased more in DHEA arms. CONCLUSION: DHEA resulted in increased hormone concentrations, though still in the lowest half or quartile of the postmenopausal range, and provided more favorable effects on vaginal cytology, compared to PM. Estrogen concentrations in women on AIs were not changed. Further research on the benefit of vaginal DHEA is warranted in hormone-dependent cancers.

Clinical performance of LOCI™-based tumor marker assays for tumor markers CA 15-3, CA 125, CEA, CA 19-9 and AFP in gynecological cancers.

Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of value in discriminating benign and malignant cervical diseases. Carcinoembryonic antigen and alpha-fetoprotein distinguished precancerous breast and vulva diseases from healthy controls. These findings show that luminescent oxygen channeling immunoassays-based tumor marker assays provide reliable results in routine diagnostics.

Is the neutrophil-to-lymphocyte ratio prognostic of survival outcomes in gynecologic cancers? A systematic review and meta-analysis.

BACKGROUND: Presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in several malignancies. Here, we quantify the effect of NLR on survival in patients with gynecologic cancers, and examine the effect of clinico-pathologic factors on its prognostic value. METHODS: A systematic search of electronic databases was conducted to identify publications exploring the association of pre-treatment blood NLR with overall survival (OS) and event-free survival (EFS) among patients with ovarian, endometrial and cervical cancers. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) or a p-value (P) were weighted by generic inverse-variance and pooled in a random effects meta-analysis. Subgroup analyses were conducted according to primary tumor type. Meta-regression was performed to evaluate the influence of clinico-pathologic factors on the HR for OS and EFS. All statistical tests were two-sided. RESULTS: Twenty-six studies comprising 10,530 patients were included. Studies used different cut-offs to classify high NLR (range 0.89 to 5.03). The median cut-off for high NLR was 2.95 among twenty-six studies reporting a HR for OS, and 2.79 in seventeen studies reporting EFS outcomes. NLR greater than the cut-off was associated with worse OS (HR 1.65, 95% CI=1.44 to 1.89; P<0.001) and EFS (HR 1.57, 95% CI=1.35 to 1.82; P<0.001). This association was present in all tumor types. Most studies were comprised of patients with both early-stage and advanced disease. In cervical cancer, significant associations between NLR and OS were observed in studies of early- and mixed-stage patients and regression analysis showed a greater magnitude of effect in patients with locally advanced disease and in those who received both chemotherapy and radiation. CONCLUSIONS: High NLR is associated with an adverse OS and EFS in patients with gynecologic malignancies.

Combined detection of tumor markers and serum inflammatory factors in the diagnosis and treatment of gynecologic oncology.

In recent years, gynecologic cancer has become the third leading cause of death for women world-wide. Serum tumor markers and inflammatory factors have been shown to be useful in the diagnosis of gynecological tumors. Therefore, the clinical value of the combined detection of tumor markers and serum inflammatory factors in the diagnosis of gynecologic oncology was studied. One hundred patients with gynecological tumors admitted to our hospital were selected as the tumor group, and 50 healthy volunteers were selected as the control group. According to clinical diagnosis, the tumor group was divided into a malignant tumor group and a benign tumor group. The levels of CA199, CA125, and CEA in each serum were measured by the Elecsys2010 automatic electrochemiluminescence immunoassay system. The levels of serum TNF-α and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that, when compared with the control group, the levels of CA199, CA125, CEA, TNF-α, and IL-17 in serum of the benign tumor group were significantly increased (P<0.001), and were further increased in the malignant tumor group. Moreover, the positive detection rates of combined detection of CA199, CA125, CEA, TNF-α, and IL-17 for malignant and benign tumors were significantly higher than that of single detection (P<0.05), and the positive detection rate of combined detection of malignant tumors was significantly higher than that of benign tumors (P<0.05). These results indicate that the combined detection of inflammatory factors and tumor markers has a high clinical value in the diagnosis and treatment of gynecological tumors and is worth adopting.

Venous Thromboembolism in Gynecological Malignancy.

OBJECTIVE: Venous thromboembolism (VTE) is a recognized complication of gynecological malignancy and represents a leading cause of morbidity and mortality in these patients. The review aimed to discuss the incidence, risk factors, and clinical presentation of VTE before examining the literature on the diagnosis, prevention, and management in the context of uterine, cervical, ovarian, and vulval cancers. METHODS/MATERIALS: A literature search was performed using Ovid Medline and Embase with the following words: "gynecological malignancy," "pelvic tumor," "venous thromboembolism," "deep vein thrombosis" and "pulmonary embolism." RESULTS: The incidence of VTE in patients with gynecological malignancy ranged between 3% and 25% and was affected by several patient and tumor factors. Duplex ultrasonography is currently the first-line imaging modality for deep venous thrombosis with sensitivity and specificity of up to 95% and 100%, respectively. Low-molecular-weight heparin is currently the VTE prophylaxis and treatment of choice for patients with gynecological malignancy, although warfarin and unfractionated heparin play a role in selected circumstances. The relatively new direct oral anticoagulants including factor Xa inhibitors and direct thrombin inhibitors are increasingly being used, although further evaluations are required, particularly in cancer patients. Catheter-directed thrombolysis and percutaneous mechanical and surgical thrombectomy may have a role in treating patients with severe symptomatic iliocaval or iliofemoral deep venous thrombosis. Overall, VTE is a poor prognosis marker in patients with gynecological malignancy. CONCLUSIONS: Gynecological malignancy-associated VTE is associated with significant morbidity, contributing to a large number of life years lost. Although promising new therapies are emerging, a 2-pronged approach is required to simultaneously target cancer-specific management and predict early on those who are likely to be affected. In the meantime, clinicians should continue to combine current guidelines with a multidisciplinary team approach to ensure that these complex patients receive the best evidence-based and compassionate care.

Rivaroxaban Used in the Treatment Patients With Gynecologic Cancer and Venous Thromboembolism: The Experience of Instituto Nacional de Câncer-Rio de Janeiro, Brazil.

INTRODUCTION: Venous thromboembolism (VTE) is a major complication of malignant diseases and is a frequent cause of death in patients with cancer. Managing anticoagulation in these patients is challenging because of the high risk of recurrent VTE and bleeding events. Rivaroxaban is an oral anticoagulant that provides rapid onset of anticoagulation. OBJECTIVE: The aim of this study was to describe the complications of rivaroxaban and potentially associated factors in patients with gynecologic cancer and VTE. METHODS: This was an observational study in women with gynecological cancer who developed VTE and were treated with 15 and 20 mg rivaroxaban at Instituto Nacional de Câncer from July 2014 to July 2015. RESULTS: Forty-one patients were treated with rivaroxaban. Most patients were younger than 60 years and presented cervical cancer; 58.5% of women did not have complications, thus remaining at a dose of 20 mg/d. Because of complications, 12.2% had the dose reduced to 15 mg/d, 12.2% had the drug suspended, 7.3% had progressive worsening of the disease with suspension of anticoagulation, and 9.8% progressed to death because of progression of the disease. CONCLUSIONS: Rivaroxaban has been documented as a low-cost, easily controlled option compared with standard therapy. Most participants in this study had no complications. However, it was not possible to assess associations with statistical significance. Further analytical studies with larger samples are required to evaluate the safety and efficacy of this treatment in patients with gynecologic cancer.

Incidence of Venous Thromboembolism by Type of Gynecologic Malignancy and Surgical Modality in the National Surgical Quality Improvement Program.

BACKGROUND: Women with gynecologic cancer are at higher risk of venous thromboembolism (VTE) due to malignancy, pelvic surgery, increased age, and frequently comorbidities. The rate of VTE among different gynecologic cancers and relative to benign gynecologic surgeries has not been reported in a nationally representative cohort. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, gynecologic surgeries were identified retrospectively from 2006 to 2012. Clinical characteristics, surgical procedures, and 30-day postoperative complications were abstracted. Multivariable logistic regression models were performed. RESULTS: Of all gynecologic surgeries (n = 104,368), 11,427 were performed for malignancy: 2.7% (n = 2800) for ovarian cancer, 6.8% (n = 7114) for uterine cancer, 1.0% (n = 1026) for cervical cancer, and 0.5%(n = 487) for vulvar cancer. 202 (1.8%) patients experienced a VTE. Ovarian cancer had a deep venous thrombosis and pulmonary embolism rates of 1.6% and 1.5% compared with uterine cancer, 0.8% and 0.8%, respectively. Ovarian cancer patients were 1.8 (95% confidence interval [CI], 1.19-2.65) times more likely to have a deep venous thrombosis and 1.7 (95% CI, 1.11-2.51) times more likely to have a pulmonary embolism than patients with uterine cancer. Compared with all gynecologic cancer surgeries, ovarian cancer patients were 1.5 times more likely to have a VTE (95% CI, 1.10-2.16). Patients undergoing minimally invasive surgery were 64% less likely to have a VTE regardless of malignancy site; however, if they had disseminated disease, they remained at higher risk of VTE (odds ratio, 5.96; P = 0.027). CONCLUSIONS: Of gynecologic cancer surgeries, ovarian cancer patients had the highest rate of VTE. Venous thromboembolism rates were lower in those who had minimally invasive surgery but remained higher in those with disseminated disease.

Preoperative elevated platelet count and thrombocytosis in gynecologic malignancies.

PURPOSE: Platelets have multiple functions and they also play an important role in malignancies. Elevated platelet count and thrombocytosis at the time of diagnosis in patients with many solid tumors correlates with prognosis and is associated with poor survival. The aim of the following report is to review the literature concerning elevated platelet count and thrombocytosis in gynecologic malignancies. METHOD: A PubMed search of all English literature peer-reviewed publications was performed containing the terms elevated platelet count or thrombocytosis and vulvar cancer, cervical cancer, endometrial cancer, and ovarian cancer. All studies published until December 31, 2015, were included in the following review. RESULTS: A pretreatment elevated platelet count and thrombocytosis have been shown to be associated with a poor prognosis in many studies of gynecologic malignancies with the exception of vulvar carcinoma. CONCLUSION: Since elevated platelet count and thrombocytosis may be prevented by blocking thrombopoietic cytokines, their assessment may, in the future, be of therapeutic significance.

Hematological toxicity of carboplatin for gynecological cancer according to body mass index.

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.