Feasibility and safety of planned early discharge following laparotomy in gynecologic oncology with enhanced recovery protocol including opioid-sparing anesthesia.

Objective: This study aims to evaluate the feasibility and safety of planned postoperative day 1 discharge (PPOD1) among patients who undergo laparotomy (XL) in the department of gynecology oncology utilizing a modified enhanced recovery after surgery (ERAS) protocol including opioid-sparing anesthesia (OSA) and defined discharge criteria. Methods: Patients undergoing XL and minimally invasive surgery (MIS) were enrolled in this prospective, observational cohort study after the departmental implementation of a modified ERAS protocol. The primary outcome was quality of life (QoL) using SF36, PROMIS GI, and ICIQ-FLUTS at baseline and 2- and 6-week postoperative visits. Statistical significance was assessed using the two-tailed Student's t-test and non-parametric Mann-Whitney two-sample test. Results: Of the 141 subjects, no significant demographic differences were observed between the XL group and the MIS group. The majority of subjects, 84.7% (61), in the XL group had gynecologic malignancy [vs. MIS group; 21 (29.2%), p < 0.001]. All patients tolerated OSA. The XL group required higher intraoperative opioids [7.1 ± 9.2 morphine milligram equivalents (MME) vs. 3.9 ± 6.9 MME, p = 0.02] and longer surgical time (114.2 ± 41 min vs. 96.8 ± 32.1 min, p = 0.006). No significant difference was noted in the opioid requirements at the immediate postoperative phase and the rest of the postoperative day (POD) 0 or POD 1. In the XL group, 69 patients (73.6%) were successfully discharged home on POD1. There was no increase in the PROMIS score at 2 and 6 weeks compared to the preoperative phase. The readmission rates within 30 days after surgery (XL 4.2% vs. MIS 1.4%, p = 0.62), rates of surgical site infection (XL 0% vs. MIS 2.8%, p = 0.24), and mean number of post-discharge phone calls (0 vs. 0, p = 0.41) were comparable between the two groups. Although QoL scores were significantly lower than baseline in four of the nine QoL domains at 2 weeks post-laparotomy, all except physical health recovered by the 6-week time point. Conclusions: PPOD1 is a safe and feasible strategy for XL performed in the gynecologic oncology department. PPOD1 did not increase opioid requirements, readmission rates compared to MIS, and patient-reported constipation and nausea/vomiting compared to the preoperative phase.

Trends in Incidence and Mortality Rates of Uterine Cancer in Kentucky.

OBJECTIVES: The objective of this analysis was to gauge how the incidence and mortality of uterine cancer in Kentucky have changed from 1995 through 2017. An assessment of the trends in incidence and mortality across different geographic areas and between different races was also performed. METHODS: Age-adjusted annual incidence and mortality rates for uterine cancer were obtained from the Kentucky Cancer Registry. A meta-regression framework was used to assess changes in incidence and mortality rates during the time frame and to determine differences in these rates between rural versus urban counties, Appalachian versus non-Appalachian counties, and Black versus White women. RESULTS: The incidence of uterine cancer has significantly increased throughout the state of Kentucky since 1995. Uterine cancer incidence was 10% and 22% higher in rural and Appalachian counties, respectively, compared with urban and non-Appalachian counties (P < 0.0001) from 1995 through 2017. In contrast, urban and non-Appalachian women had higher or equivalent age-adjusted mortality from uterine cancer, compared with rural and Appalachian women, respectively. The incidence of uterine cancer was significantly higher in White women compared with Black women from 1995 through 2006, but since 2007, there has been no significant difference in uterine cancer incidence based on race. Black women had higher age-adjusted mortality than White women throughout the entire time period examined. CONCLUSIONS: The incidence of uterine cancer is higher in rural and Appalachian Kentucky, without a corresponding geographic trend in mortality. Uterine cancer mortality is significantly higher in Black women.

Vaginal cuff brachytherapy: do we need to treat to more than a two-centimeter active length?

PURPOSE: American Brachytherapy Society (ABS) guidelines recommend using a 3-5 cm active length (AL) when treating vaginal cuff (VC) in adjuvant setting of endometrial cancer (EC). The purpose of this study was to evaluate local control and toxicity, using an AL of 1 or 2 cm and immobilization with a traditional table-mounted (stand) or patient-mounted (suspenders) device. MATERIAL AND METHODS: Between 2005 and 2019, 247 patients with EC were treated with adjuvant high-dose-rate vaginal cuff (HDR-VC) brachytherapy with or without external beam radiation (EBRT). Treatment was prescribed to a 0.5 cm depth, with an AL of 1 or 2 cm, using stand or suspenders. VC boost after EBRT was typically administered with 2 fractions of 5.5 Gy, while VC brachytherapy alone was typically applied with 3 fractions of 7 Gy or 5 fractions of 5.5 Gy. RESULTS: The combination of suspender immobilization and an AL of 2 cm (n = 126, 51%) resulted in 5-year local control of 100%. An AL of 2 cm compared to 1 cm correlated with better local control (99.1% vs. 88.5%, p = 0.0479). Regarding immobilization, suspenders correlated with improved local control compared to stand (100% vs. 86.7%, p = 0.0038). Immobilization technique was significantly correlated with AL (p < 0.0001). Only 5 (2.0%) patients experienced grade ≥ 3 toxicity, all of whom received EBRT. CONCLUSIONS: In the present series, an AL of 2 cm provided excellent local control, while 1 cm was inadequate. Suspender immobilization was a practical alternative to stand immobilization in HDR brachytherapy of the vaginal cuff.

Role of adjuvant chemotherapy in patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with surgery and post-operative radiotherapy.

BACKGROUND: The optimal treatment of patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma remains unknown. OBJECTIVE: To compare overall survival following treatment with a hysterectomy and adjuvant radiotherapy with or without chemotherapy in this group of patients. METHODS: Patients diagnosed between January 2004 and January 2016 with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with hysterectomy and postoperative radiotherapy with or without adjuvant concurrent chemotherapy were identified in the National Cancer Database. Overall survival was assessed with Kaplan-Meier curves. A Cox model was constructed to evaluate survival after controlling for confounding variables. A logistic regression model was used to reveal predictors of chemotherapy use. RESULTS: A total of 2173 patients were included. The receipt of chemotherapy was associated with an increased 5-year overall survival from 67.6% to 75.6% (p=0.0313). This association trended toward statistical significance on multivariate analysis (adjusted HR (aHR) 0.80; 95% CI 0.63 to 1.01; p=0.0653). Other factors associated with improved survival were undergoing a lymphadenectomy, absence of lymphovascular space invasion, younger age, smaller tumor size, non-black race, and absence of comorbidities. Patients who underwent brachytherapy, had lymphovascular space invasion, were younger, were diagnosed in the more recent years, and were treated in higher volume centers were more likely to receive adjuvant chemotherapy. CONCLUSION: Adjuvant chemotherapy and radiation therapy were associated with an increase in survival in patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma compared with those treated with adjuvant radiotherapy alone.

The impact of brachytherapy boost and radiotherapy treatment duration on survival in patients with vaginal cancer treated with definitive chemoradiation.

PURPOSE: Vaginal cancer is a rare tumor that is optimally treated with a combination of chemotherapy (CHT) and radiation therapy. Because of the rarity of this cancer, the benefit of a brachytherapy boost (BT) and the relevance of radiotherapy time to treatment completion (TTC) are unclear. METHODS: Patients diagnosed between 2004 and 2015 with non-metastatic vaginal cancer treated with definitive CHT and external beam radiotherapy with or without BT but with no surgery were identified in the National Cancer Database. Overall survival (OS) was assessed with Kaplan-Meier curves, and differences between groups were compared with the log-rank test. A Cox model was constructed to evaluate survival after controlling for confounders. A Cox model using a penalized spline function was constructed to evaluate how the length of radiation therapy correlated with OS among patients receiving BT. RESULTS: A total of 1094 patients who met the inclusion criteria were identified. The utilization of BT was associated with improved 5-year OS (62.9% vs. 49.3%, p = 0.0126) on propensity score-weighted analyses. TTC of 63 days or less was associated with improved 5-year OS (67.8% vs. 54.5%, p = 0.0031) in patients who underwent BT. Other factors associated with improved OS in patients who received CHT, external beam radiotherapy, and BT were younger age, absent comorbidity score, and negative lymph nodes. CONCLUSIONS: A brachytherapy boost and shorter TTC were associated with a survival benefit in a cohort of patients with non-metastatic vaginal cancer treated with definitive chemoradiotherapy.

Cervical cancer incidence and mortality rates in Kentucky.

OBJECTIVES: The goal of this study was to assess how the incidence and mortality of cervical cancer in Kentucky has changed from 1995 through 2017. Additionally, trends in incidence and mortality across different geographic areas and between different races were evaluated. METHODS: Age-adjusted annual incidence and mortality rates for cervical cancer were collected from the Kentucky Cancer Registry (KCR). A quadratic fit model was used to evaluate changes in the incidence and mortality over time and to compare differences in cervical cancer incidence and mortality by: 1) rural versus urban counties, 2) Appalachian versus non-Appalachian counties, and 3) black versus white women. RESULTS: Overall, the incidence of cervical cancer has significantly decreased throughout Kentucky since 1995. When comparing different geographic regions, the incidence was 14% and 23% higher in rural and Appalachian counties, respectively, compared to urban and non-Appalachian counties (p < 0.0001) throughout the study period. The incidence of cervical cancer was significantly higher in black women compared to white women from 1995 through 2007, but since 2008 there has been no significant difference in cervical cancer incidence based on race. Similar to incidence rates, mortality from cervical cancer was 29% higher in Appalachia (p = 0.0004) throughout the studied time period. Black women had higher age-adjusted mortality than white women until 2012, but since that time there has not been a significant difference in cervical cancer mortality based on race. CONCLUSIONS: Women residing in rural and Appalachian Kentucky have higher cervical cancer incidence and mortality rates.

Expression of the BAD pathway is a marker of triple-negative status and poor outcome.

Triple-negative breast cancer (TNBC) has few therapeutic targets, making nonspecific chemotherapy the main treatment. Therapies enhancing cancer cell sensitivity to cytotoxic agents could significantly improve patient outcomes. A BCL2-associated agonist of cell death (BAD) pathway gene expression signature (BPGES) was derived using principal component analysis (PCA) and evaluated for associations with the TNBC phenotype and clinical outcomes. Immunohistochemistry was used to determine the relative expression levels of phospho-BAD isoforms in tumour samples. Cell survival assays evaluated the effects of BAD pathway inhibition on chemo-sensitivity. BPGES score was associated with TNBC status and overall survival (OS) in breast cancer samples of the Moffitt Total Cancer Care dataset and The Cancer Genome Atlas (TCGA). TNBC tumours were enriched for the expression of phospho-BAD isoforms. Further, the BPGES was associated with TNBC status in breast cancer cell lines of the Cancer Cell Line Encyclopedia (CCLE). Targeted inhibition of kinases known to phosphorylate BAD protein resulted in increased sensitivity to platinum agents in TNBC cell lines compared to non-TNBC cell lines. The BAD pathway is associated with triple-negative status and OS. TNBC tumours were enriched for the expression of phosphorylated BAD protein compared to non-TNBC tumours. These findings suggest that the BAD pathway it is an important determinant of TNBC clinical outcomes.

Arsenite and Cadmium Activate MAPK/ERK via Membrane Estrogen Receptors and G-Protein Coupled Estrogen Receptor Signaling in Human Lung Adenocarcinoma Cells.

Epidemiological evidence indicates that cadmium and arsenic exposure increase lung cancer risk. Cadmium and arsenic are environmental contaminants that act as endocrine disruptors (EDs) by activating estrogen receptors (ERs) in breast and other cancer cell lines but their activity as EDs in lung cancer is untested. Here, we examined the effect of cadmium chloride (CdCl2) and sodium arsenite (NaAsO2) on the proliferation of human lung adenocarcinoma cell lines. Results demonstrated that both CdCl2 and NaAsO2 stimulated cell proliferation at environmentally relevant nM concentrations in a similar manner to 17ß-estradiol (E2) in H1793, H2073, and H1944 cells but not in H1792 or H1299 cells. Further studies in H1793 cells showed that 100 nM CdCl2 and NaAsO2 rapidly stimulated mitogen-activated protein kinase (MAPK, extracellular-signal-regulated kinases) phosphorylation with a peak detected at 15 min. Inhibitor studies suggest that rapid MAPK phosphorylation by NaAsO2, CdCl2, and E2 involves ER, Src, epidermal growth factor receptor, and G-protein coupled ER (GPER) in a pertussis toxin-sensitive pathway. CdCl2 and E2 activation of MAPK may also involve ERß. This study supports the involvement of membrane ER and GPER signaling in mediating cellular responses to environmentally relevant nM concentrations of CdCl2 and NaAsO2 in lung adenocarcinoma cells.