Wait-time for hysterectomy and survival of women with early-stage cervical cancer: A clinical implication during the coronavirus pandemic.

OBJECTIVE: A global pandemic caused by a novel coronavirus (Covid-19) has created unique challenges to providing timely care for cancer patients. In early-stage cervical cancer, postponing hysterectomy for 6-8 weeks is suggested as a possible option in the Covid-19 burdened hospitals. Yet, literature examining the impact of surgery wait-time on survival in early-stage cervical cancer remains scarce. This study examined the association between surgery wait-time of 8 weeks and oncologic outcome in women with early-stage cervical cancer. METHODS: This is a single institution retrospective observational study at a tertiary referral medical center examining women who underwent primary hysterectomy or trachelectomy for clinical stage IA-IIA invasive cervical cancer between 2000 and 2017 (N = 217). Wait-time from the diagnosis of invasive cervical cancer via biopsy to definitive surgery was categorized as: short wait-time (<8 weeks; n = 110) versus long wait-time (≥8 weeks; n = 107). Propensity score inverse probability of treatment weighting was used to balance the measured demographics between the two groups, and disease-free survival (DFS) and overall survival (OS) were assessed. A systematic literature review with meta-analysis was additionally performed. RESULTS: In a weighted model (median follow-up, 4.6 years), women in the long wait-time group had DFS (4.5-year rates, 91.2% versus 90.7%, hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.47-2.59, P = 0.818) and OS (95.0% versus 97.4%, HR 1.47, 95%CI 0.50-4.31, P = 0.487) similar to those in the short wait-time group. Three studies were examined for meta-analysis, and a pooled HR for surgery wait-time of ≥8 weeks on DFS was 0.96 (95%CI 0.59-1.55). CONCLUSION: Our study suggests that wait-time of 8 weeks for hysterectomy may not be associated with short-term disease recurrence in women with early-stage cervical cancer.

Association of statins, aspirin, and venous thromboembolism in women with endometrial cancer.

OBJECTIVE: The anti-thrombogenic effects of statins and aspirin have been reported in various malignancies but have not been well examined in endometrial cancer. This study examined the association between statin and/or aspirin use and venous thromboembolism (VTE) risk in endometrial cancer. METHODS: This is a multi-center retrospective study examining 2527 women with endometrial cancer between 2000 and 2015. Statin and aspirin use at diagnosis was correlated to VTE risk during follow-up on multivariable analysis. RESULTS: There were 132 VTE events with a 5-year cumulative incidence rate of 6.1%. There were 392 (15.5%) statin users and 219 (8.7%) aspirin users, respectively. On multivariable analysis, statin use was associated with an approximately 60% decreased risk of VTE when compared to non-users (5-year cumulative rates 2.5% versus 6.7%, adjusted-hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.19-0.92, P = 0.030) whereas aspirin did not demonstrate statistical significance (2.0% versus 6.5%, adjusted-HR 0.54, 95%CI 0.19-1.51, P = 0.24). There was a trend of joint effect between statin and aspirin although it did not demonstrate statistical significance: VTE risks for dual statin/aspirin user (adjusted-HR 0.27, 95%CI 0.04-2.07), statin alone (adjusted-HR 0.40, 95%CI 0.18-0.93), and aspirin alone (adjusted-HR 0.51, 95%CI 0.16-1.64) compared to non-use after adjusting for patient characteristics, tumor factors, treatment types, and survival events (P-interaction = 0.090). When stratified by statin type, simvastatin demonstrated the largest reduction of VTE risk (5-year cumulative rates 1.1% versus 6.7%, adjusted-HR 0.17, 95%CI 0.02-1.30, P = 0.088). Obesity, absence of diabetes mellitus, type II histology, and recurrent disease were the factors associated with decreased VTE risk with statin use (all, P-interaction<0.05). CONCLUSION: Our study suggests that statin use may be associated with decreased risk of VTE in women with endometrial cancer.

Prolonged intubation after robotic-assisted hysterectomy for endometrial cancer: Case reports.

•Experienced prolonged intubation after robotic hysterectomy for endometrial cancer•Risk triad: Trendelenburg position, high pneumo-pressure, and excess hydration•Recognition of the risk triad is key to avoiding airway complications in robotic surgery.•Introduction of a 5-step method to prevent airway complications in robotic surgery.

Significance of abnormal peritoneal cytology on survival of women with stage I-II endometrioid endometrial cancer.

OBJECTIVE: To examine survival of women with stage I-II endometrioid endometrial cancer whose peritoneal cytology showed malignant or atypical cells (abnormal peritoneal cytology). METHODS: This is a multi-center retrospective study examining 1668 women with stage I-II endometrioid endometrial cancer who underwent primary hysterectomy with available peritoneal cytology results between 2000 and 2015. Abnormal peritoneal cytology was correlated to clinico-pathological characteristics and oncological outcome. RESULTS: Malignant and atypical cells were seen in 125 (7.5%) and 58 (3.5%) cases, respectively. On multivariate analysis, non-obesity, non-diabetes mellitus, cigarette use, and lympho-vascular space invasion were independently associated with abnormal peritoneal cytology (all, P<0.05). Abnormal peritoneal cytology was independently associated with decreased disease-free survival (hazard ratio 3.07, P<0.001) and cause-specific survival (hazard ratio 3.42, P=0.008) on multivariate analysis. Abnormal peritoneal cytology was significantly associated with increased risks of distant-recurrence (5-year rates: 8.8% versus 3.6%, P=0.001) but not local-recurrence (5.2% versus 3.0%, P=0.32) compared to negative cytology. Among women with stage I disease, abnormal peritoneal cytology was significantly associated with an increased risk of distant-recurrence in the low risk group (5-year rates: 5.5% versus 1.0%, P<0.001) but not in the high-intermediate risk group (13.3% versus 10.8% P=0.60). Among 183 women who had abnormal peritoneal cytology, postoperative chemotherapy significantly reduced the rate of peritoneal recurrence (5-year rates: 1.3% versus 9.2%, P=0.039) whereas postoperative radiotherapy did not (7.1% versus 5.5%, P=0.63). CONCLUSION: Our study suggests that abnormal peritoneal cytology may be a prognostic factor for decreased survival in women with stage I-II endometrioid endometrial cancer, particularly for low-risk group.

Intrauterine Manipulator Use During Minimally Invasive Hysterectomy and Risk of Lymphovascular Space Invasion in Endometrial Cancer.

OBJECTIVE: This study aimed to examine an association between intrauterine manipulator (IUM) use and frequency of lymphovascular space invasion (LVSI) in women with endometrial cancer undergoing minimally invasive hysterectomy. METHODS: A retrospective case-control study was conducted among stage I-IV endometrial cancer patients who underwent hysterectomy between 2008 and 2015. Medical records were reviewed for patient demographics, surgical details, and tumor characteristics. Women who underwent total laparoscopic hysterectomy (TLH) with IUM use were compared with women who underwent total abdominal hysterectomy (TAH). Review of archived medical record for data collection and propensity score matching were performed to adjust for background differences between TLH-IUM and TAH groups. A systematic literature review with pooled analysis was performed to examine frequency of LVSI. RESULTS: There were 687 women who underwent hysterectomy for endometrial cancer. Of those, 419 women underwent TLH with IUM use and 194 women underwent TAH. The most common type of IUM was VCare (89.5%). There was no statistically significant difference in the frequency of LVSI between the 2 groups: 15.1% for TLH-IUM vs 19.9% for TAH (P = 0.14). After propensity score matching, frequencies of LVSI were similar between the 2 groups: 21.2% for TLH-IUM vs 19.6% for TAH (P = 0.78). Systematic literature review identified 1371 cases of TLH-IUM and 1246 cases of TAH performed for endometrial cancer, and frequencies of LVSI were similar between the 2 groups (15.0% vs 13.6%, P = 0.31). CONCLUSION: Our study suggests that IUM use during TLH for endometrial cancer is not associated with increased frequency of LVSI.

Association of Metformin Use and Survival Outcome in Women With Cervical Cancer.

OBJECTIVE: Although preclinical studies suggest possible antitumor effects of metformin against cervical cancer, there is currently a lack of clinical data examining the association of metformin use and survival in women with cervical cancer. The aim of this study was to examine survival of women with cervical cancer who were receiving metformin. METHODS: This is a retrospective study examining consecutive cases of stages I to IV cervical cancer between 2000 and 2014. Patient demographics, medication use, tumor characteristics, treatment patterns, and survival outcomes were correlated to metformin use. RESULTS: There were 70 (8.9%; 95% confidence interval [CI], 6.9-10.9) metformin users and 715 nonusers identified for the analysis. Median follow-up time was 22.6 months. Recurrence/progression of disease and death due to cervical cancer were observed in 236 and 163 cases, respectively. Metformin users were more likely to be older, hypertensive, diabetic, and dyslipidemic compared with nonusers (all, P < 0.05). On univariate analysis, metformin users and nonusers had similar progression-free survival (PFS) (5-year rates; 57.3% vs 61.8%; P = 0.82) and cervical cancer-specific overall survival (71.7% vs 70.7%; P = 0.86). After adjusting for patient demographics and tumor characteristics, metformin use was not associated with PFS (adjusted hazards ratio, 1.11; 95% CI, 0.70-1.74; P = 0.67) or cervical cancer-specific overall survival (adjusted hazards ratio, 0.91; 95% CI, 0.52-1.60; P = 0.75). Among 478 women who received whole pelvic radiotherapy, metformin use was not associated with PFS (P = 0.93) or cervical cancer-specific overall survival (P = 0.32). CONCLUSIONS: In this study population, metformin use was not associated with survival of women with cervical cancer.

Predictive model of urinary tract infection after surgical treatment for women with endometrial cancer.

PURPOSE: The aim of the study was to identify risk factors associated with postoperative urinary tract infections (UTIs) following hysterectomy-based surgical staging in women with endometrial cancer. METHODS: This is a retrospective study utilizing an institutional database (2008-2016) of stage I-IV endometrial cancer cases that underwent hysterectomy-based surgery. UTIs occurring within a 30-day time period after surgery were examined and correlated to patient clinico-pathological demographics. RESULTS: UTIs were observed in 44 (6.4%, 95% confidence interval 4.6-8.2) out of 687 cases subsequent to the diagnosis of endometrial cancer. UTI cases were significantly associated with obesity, advanced stage, prolonged operative time, hysterectomy type, pelvic lymphadenectomy, non-ß-lactam antibiotics, and intraoperative urinary tract injury (all, p < 0.05). On multivariate analysis, three independent risk factors were identified for UTIs: prolonged operative time [odds ratio (OR) 3.36, 95% CI 1.65-6.87, p = 0.001], modified-radical/radical hysterectomy (OR 5.35, 95% CI 1.56-18.4, p = 0.008), and an absence of perioperative ß-lactam antibiotics use (OR 3.50, 95% CI 1.46-8.38, p = 0.005). In a predictive model of UTI, the presence of multiple risk factors was associated with significantly increased risk of UTI: 4.1% for the group with no risk factors, 7.3-12.5% (OR 1.85-3.37) for single risk factor group, and 30.0-30.8% (OR 10.1-10.5) for two risk factor group. CONCLUSION: Urinary tract infections are common in women following surgical treatment for women with endometrial cancer with risk factors being a prolonged surgical time, radical hysterectomy, and non-guideline perioperative anti-microbial agent use. Consideration of prophylactic anti-microbial agent use in a high-risk group of postoperative urinary tract infection merits further investigation.

Association of Nonalcoholic Fatty Liver Disease and Venous Thromboembolism in Women With Endometrial Cancer.

OBJECTIVE: Recent studies have demonstrated that surgical menopause results in a significantly increased risk of nonalcoholic fatty liver disease (NAFLD) in women with endometrial cancer. In addition, venous thromboembolism (VTE) is known to be one of the major prognostic factors for decreased survival in endometrial cancer. Given the fact that coagulation factors are produced in the liver, the correlation between NAFLD and VTE was examined in endometrial cancer. METHODS: A retrospective study was conducted to examine patients with endometrial cancer who underwent surgical staging including oophorectomy between 2000 and 2013 (n = 714). Cumulative risk of VTE was examined based on the NAFLD status. A Cox proportional hazard regression model was used to determine the independent risk predictors of VTE. RESULTS: Venous thromboembolism and NAFLD were seen in 57 (8.0%) and 181 (25.4%) cases, respectively. Two-year cumulative risks of VTE and NAFLD were 7.9% and 19.3%, respectively. In univariate analysis, VTE was significantly associated with decreased disease-free survival (2-year rate, 43.6% vs 91.4%, P < .001) and overall survival (65.8% vs 96.8%, P < .001), whereas NAFLD was associated with decreased risk of VTE (1.7% vs 10.4%, P < .001). In multivariate analysis controlling for clinicopathological factors, NAFLD remained an independent predictor of decreased risk of VTE (hazard ratio [HR]: 0.24, 95% confidence interval [CI]: 0.07-0.79, P = .02). Thrombocytosis (HR: 2.30, 95% CI: 1.22-4.35, P = .01), cancer antigen 125 ≥ 35 (HR: 3.81, 95% CI: 1.78-8.17, P < .001), and recurrent disease (HR: 4.57, 95% CI: 1.97-10.6, P < .001) remained as independent predictors of increased risk of VTE. CONCLUSION: Our results suggest that NAFLD may be associated with decreased VTE risk in women with endometrial cancer.

Significance of Monocyte Counts at Recurrence on Survival Outcome of Women With Endometrial Cancer.

OBJECTIVE: Tumor-associated macrophages (TAMs) are known to have adverse effects on the survival of women with endometrial cancer. Because monocytes function as progenitors of macrophages, this study examined the association between monocyte count at the first recurrence/progression of endometrial cancer and survival time after recurrence/progression (SAR). METHODS: This is a retrospective study evaluating 141 consecutive cases of recurrent endometrial cancer after surgical staging (n = 114) and progression after nonsurgical management (n = 27). Complete blood cell counts with cell differentiation at the time of the first recurrence/progression were correlated to SAR. RESULTS: Median time of SAR was 7.8 months, and there were 97 (68.8%) patients who died from endometrial cancer with 1-, 2-, and 5-year SAR rates being 51.0%, 32.9%, and 14.2%, respectively. Median monocyte counts at recurrence/progression were 0.5 × 10/L. The strongest correlation to monocyte counts was seen in neutrophil counts (r = 0.57, P < 0.01) followed by platelet counts (r = 0.43, P < 0.01). An elevated monocyte count at recurrence/progression was significantly associated with decreased SAR (hazard ratio per unit, 3.97; 95% confidence interval, 2.00-7.90; P < 0.01). On multivariate analysis controlling for patient demographics, complete blood cell counts, tumor factors, and treatment types for recurrent/progressed disease, higher monocyte counts at recurrence/progression remained an independent predictor for decreased SAR (hazard ratio per unit, 3.12; 95% confidence interval, 1.52-6.67; P < 0.01). CONCLUSIONS: Our study demonstrated that the increased monocyte counts at recurrence/progression may be a useful biomarker for predicting decreased survival outcome of women with endometrial cancer.

Signs and Symptoms of Venous Thromboembolism and Survival Outcome of Endometrial Cancer.

OBJECTIVE: This study aimed to evaluate if the presence of venous thromboembolism (VTE) diagnosed with subjective and objective measurements correlates with the survival outcome in patients with endometrial cancer. METHODS: A retrospective study was conducted on patients with endometrial cancer who developed VTE between cancer diagnosis and follow-up from 1999 to 2013. Disease-specific survival after VTE diagnosis was evaluated according to VTE symptoms and vital signs. RESULTS: Among 827 endometrial cancer cases during the study period, there were 72 (8.7%) patients with VTE identified (pulmonary embolism [PE] with or without deep vein thrombosis [DVT], n = 34; and DVT alone n = 38). In the PE group, decreased disease-specific survival after the diagnosis of VTE was associated with fatigue, systolic blood pressure (BP) less than 120 mm Hg, diastolic BP less than 70 mm Hg, and a heart rate 90 beats per minute or greater (all, P < 0.05) in a univariate analysis. Symptomatic PE was associated with decreased survival as compared to asymptomatic PE (2-year rate; 23.1% vs 77.8%, P < 0.01). In a multivariate analysis controlling for symptoms of VTE, signs, and tumor factors, a diastolic BP less than 70 mm Hg (adjusted-hazard ratio [HR], 10.0; 95% confidence interval, 2.70-37.1; P < 0.01) and HR greater than 90 beats per minute (adjusted-HR, 8.06; 95% confidence interval, 2.36-27.5; P < 0.01) remained as independent prognostic factors for decreased disease-specific survival after PE diagnosis. Patients with PE presenting with low diastolic BP and high heart rate resulted in a dismal survival outcome (diastolic BP < 70 mm Hg/heart rate ≥ 90 beats per minute vs diastolic BP ≥ 70 mm Hg/heart rate < 90 beats per minute; 0% vs 85.7%, P < 0.01). In the group of patients with DVT alone, no signs or symptoms correlated with survival outcome (all, P > 0.05). CONCLUSIONS: Our results suggested that both signs and symptoms of PE are important consideration in the management of patients with endometrial cancer with PE.

Predictive Factor of Conversion to Laparotomy in Minimally Invasive Surgical Staging for Endometrial Cancer.

OBJECTIVE: The aim of the study was to identify risk factors associated with laparotomy conversion during total laparoscopic hysterectomy for endometrial cancer. METHODS: This is a retrospective study examining endometrial cancer cases that underwent hysterectomy-based surgical staging initiated via conventional laparoscopic approach. Factors related to patient, tumor, and surgeon were examined to establish risk of laparotomy conversion using a multivariate logistic regression model. RESULTS: There were 251 cases identified including 30 cases (12.0%) of laparotomy conversion. The most common indication for laparotomy conversion was a large uterus (27.0%), followed by extensive adhesions (24.3%) and surgical complications (18.9%). Outcomes of cases resulting in laparotomy conversion include longer surgical time (333 vs 224 minutes, P < 0.001), larger blood loss (350 vs 100 mL, P < 0.001), longer hospital stay (4 vs 2 days, P < 0.001), and increased risk of hospital readmission (10% vs 1.4%, P = 0.024). In multivariate analysis, morbid obesity (odds ratio [OR], 4.51; P = 0.011), suboptimal pelvic examination or enlarged uterus during preoperative evaluation (OR, 3.55; P = 0.034), para-aortic lymphadenectomy (OR, 10.5; P = 0.001), uterine size 250 g or greater (OR, 3.49; P = 0.026), and extrauterine disease (OR, 4.68; P = 0.012) remained the independent predictors for laparotomy conversion. The following numbers of risk factors were significantly correlated with laparotomy-conversion rate: none, 1.1%; single risk factor, 5.3% (OR, 5.00; P = 0.15); double risk factors, 21.7% (OR, 24.9; P = 0.002); and triple or more risk factors, 50% (OR, 90.0; P < 0.001). Ultrasonographic 3-dimensional volumes of 496 cm in preoperative uterine size correlate with actual uterine weight of 250 g (Y = 61.5 + 0.38X, P < 0.001). CONCLUSIONS: Laparotomy conversion significantly impacts outcomes of patients with endometrial cancer. In this setting, our predictive model for laparotomy conversion will be useful to guide the surgical management of endometrial cancer.

Relative Morbidity and Mortality of Panniculectomy-Combined Surgical Staging in Endometrial Cancer.

OBJECTIVE: To examine intraoperative and postoperative complication rates for surgical staging combined with panniculectomy for endometrial cancer. METHODS: A prospectively collected institutional surgical database was used to identify patients with endometrial cancer who underwent hysterectomy-based surgical staging between December 2008 and August 2014 (n = 551). The cases were grouped into surgical staging with panniculectomy (panniculectomy group, n = 11 [2.0%]), laparotomy without panniculectomy (laparotomy group, n = 208 [37.7%]), and laparoscopy (minimally invasive surgery group, n = 332 [60.3%]). Major complication and surgical wound complication rates within 30 days from surgery were compared. RESULTS: The panniculectomy group had a significantly higher body mass index compared with other approaches (panniculectomy group, laparotomy group, and minimally invasive surgery group: 60.4, 35.7, and 34.1; P < 0.001) and had a high stage I disease rate (90.9%, 61.5%, and 88.3%; P < 0.001). Mean pannus weight was 5733 g (4.4% of body weight). Intraoperative major complication rates were statistically nonsignificant across the groups (0%, 7.2%, and 4.2%; P = 0.23); however, the panniculectomy group had a significantly higher postoperative major complication rate compared with other approaches (36.4%, 16.3%, and 5.1%; P < 0.001). In multivariate analysis controlling for age, ethnicity, body habitus, medical comorbidities, and tumor factors, panniculectomy remained an independent predictor for increased risk of postoperative major complications (adjusted odds ratio, 4.37; P = 0.043). Surgical mortality rates were similar across the groups (0%, 0.5%, and 0%; P = 0.44). Among superobese patients (n = 50), intraoperative and postoperative complication rates were statistically similar across the 3 groups (all, P > 0.05). CONCLUSION: Although panniculectomy-combined surgical staging is associated with an increased risk of postoperative complications, the majority recovered uneventfully, making this approach a feasible treatment option, especially for superobese patients with endometrial cancer.

Significance of monocyte counts on tumor characteristics and survival outcome of women with endometrial cancer.

OBJECTIVE: Tumor-associated macrophages are known to be associated with decreased survival of patients with endometrial cancer. Given the physiological link of circulating monocytes as a progenitor of tumor-associated macrophages, monocyte counts were examined for tumor characteristics and survival in endometrial cancer. METHODS: A retrospective study was conducted to examine consecutive patients with endometrial cancer with all histologic types who underwent hysterectomy-based surgical staging between 2003 and 2013 (n=541). Preoperative monocyte counts were correlated to patient demographics, pathological findings, complete blood count results, and survival outcomes. RESULTS: Median monocyte counts were 0.5×10(9)/L. Monocyte counts significantly correlated with all other complete blood count components, with neutrophil counts having the most significant association (r=0.52, p<0.001). Elevated monocyte counts (defined as >0.7×10(9)/L) when compared to lower counts were significantly associated with an increased risk of >50% myometrial tumor invasion (29.2% versus 22.0%, odds ratio [OR] 1.59, 95% confidence interval [CI] 1.01-2.45, p=0.045), pelvic lymph node metastasis (39.0% versus 18.8%, OR 2.76, 95%CI 1.35-5.62, p=0.007), and advanced-stage (stage I through IV, 18.5%, 24.6%, 32.5%, and 41.5%, p=0.001). In survival analysis, elevated monocyte counts were associated with decreased disease-free survival (5-year rates, 71.0% versus 84.5%, p=0.001) and overall survival (77.2% versus 89.3%, p<0.001). In multivariate analysis, elevated monocyte counts remained an independent prognostic factor for decreased disease-free (hazard ratio [HR] 1.74, 95% CI 1.02-2.96, p=0.041) and overall (HR 2.63, 95% CI 1.37-5.05, p=0.004) survival. CONCLUSIONS: Elevated monocyte counts were associated with aggressive tumor features and poor survival outcomes of patients with endometrial cancer.

Relationships between trait urgency, smoking reinforcement expectancies, and nicotine dependence.

Urgency (i.e., the tendency to act rashly during negative/positive affect) may increase vulnerability to a variety of risky behaviors. This cross-sectional study of nontreatment-seeking smokers examined the relationship between urgency, level of nicotine dependence, and smoking reinforcement expectancies. Both positive and negative urgency were associated with nicotine dependence. Mediational analyses illustrated that smoking reinforcement expectancies significantly accounted for urgency-dependence relations, with negative reinforcement expectancies displaying incremental mediational effects. If replicated and extended, these findings may support the use of treatments that modify beliefs regarding smoking reinforcement outcomes as a means of buffering the risk of nicotine dependence carried by urgency.