Preoperative quality of life and surgical outcomes in gynecologic oncology patients: a new predictor of operative risk?

OBJECTIVE: Quality of life (QoL) for women with gynecologic malignancies is predictive of chemotherapy related toxicity and overall survival but has not been studied in relation to surgical outcomes and hospital readmissions. Our goal was to evaluate the association between baseline, pre-operative QoL measures and 30-day post-operative morbidity and health resource utilization by gynecologic oncology patients. METHODS: We analyzed prospectively collected survey data from an institution-wide cohort study. Patients were enrolled from 8/2012 to 6/2013 and medical record data was abstracted (demographics, comorbid conditions, and operative outcomes). Responses from several validated health-related QoL instruments were collected. Bivariate tests and multivariable linear and logistic regression models were used to evaluate factors associated with QoL scores. RESULTS: Of 182 women with suspected gynecologic malignancies, 152 (84%) were surveyed pre-operatively and 148 (81%) underwent surgery. Uterine (94; 63.5%), ovarian (26; 17.5%), cervical (15; 10%), vulvar/vaginal (8; 5.4%), and other (5; 3.4%) cancers were represented. There were 37 (25%) cases of postoperative morbidity (PM), 18 (12%) unplanned ER visits, 9(6%) unplanned clinic visits, and 17 (11.5%) hospital readmissions (HR) within 30days of surgery. On adjusted analysis, lower functional well-being scores resulted in increased odds of PM (OR 1.07, 95%CI 1.01-.1.21) and HR (OR 1.11, 95%CI 1.03-1.19). A subjective global assessment score was also strongly associated with HR (OR 1.89, 95%CI 1.14, 3.16). CONCLUSION: Lower pre-operative QoL scores are significantly associated with post-operative morbidity and hospital readmission in gynecologic cancer patients. This relationship may be a novel indicator of operative risk.

Adverse Urinary System Outcomes among Older Women with Endometrial Cancer.

PURPOSE OF THE STUDY: Endometrial cancer and its treatment may cause damage to the urinary system, but few large-scale studies have examined the incidence of urinary-related outcomes among endometrial cancer survivors. We investigated the risk of several urinary disease diagnoses among older women with endometrial cancer compared to women without a cancer history. METHODS: Women ages 66 years and older with an endometrial cancer diagnosis during 2004-2017 (N=44,386) and women without a cancer history (N=221,219) matched 5:1 on age, race/ethnicity, and state were identified in the Surveillance, Epidemiology, and End Results-Medicare linked data. ICD-9 and -10 diagnosis codes were used to identify urinary outcomes in the Medicare claims data. Cumulative incidences (IP) of urinary outcomes were estimated among women with and without endometrial cancer. Multivariable Cox proportional hazards regression models were used to estimate hazards ratios (HR) for urinary outcomes comparing women with and without endometrial cancer. HRs were also used to identify characteristics associated with urinary outcomes among endometrial cancer survivors. RESULTS: Relative to women without cancer, endometrial cancer survivors had an increased risk of urinary system diagnoses, including renal failure (5-year IP: 25% vs 14%; HR=1.50; 95% CI: 1.47-1.53), chronic kidney disease (5-year IP: 20% vs 14%; HR=1.25; 95% CI: 1.22-1.28), calculus of the urinary tract (5-year IP: 7% vs 4%; HR=1.55; 95% CI: 1.50-1.61), lower urinary tract infection (5-year IP: 55% vs 33%; HR=1.75; 95% CI: 1.72, 1.78), and bladder diseases (5-year IP: 10% vs 6%; HR=1.57; 95% CI: 1.52, 1.62). These associations persisted in analyses limited to 1+ and 5+ years after endometrial cancer diagnosis. Non-Hispanic Black or Hispanic race/ethnicity, higher comorbidity index, higher stage or grade cancer, non-endometrioid histology, and treatment with chemotherapy and/or radiation were often predictors of urinary outcomes among women with endometrial cancer. CONCLUSIONS: Our results suggest that, among older women, the risk of urinary outcomes is elevated after endometrial cancer. Monitoring for urinary diseases may be a critical part of long-term survivorship care for older women with an endometrial cancer history.

Hepatocyte growth factor stimulates trophoblast invasion: a potential mechanism for abnormal placentation in preeclampsia.

Hepatocyte growth factor (HGF) is a cytokine that is produced in the placental villous core and acts in a paracrine manner on trophoblasts that express the HGF receptor Met. Because HGF stimulates the invasion of many epithelial cell types, villous core HGF could regulate placental trophoblast invasion. As preeclampsia is characterized by inadequate trophoblast invasion, we investigated the hypothesis that decreased placental HGF production is a mechanism for inadequate trophoblast invasion in this disease. Placental villous explant HGF production over 24 h was 25% lower in patients with preeclampsia (n = 5; 7.29 +/- 0.8 ng/mL) than in normal patients (n = 5; 9.76 +/- 0.5 ng/mL; P < 0.05). The human first trimester trophoblast cell line (ED27) used in subsequent invasion studies was found to express c-met messenger ribonucleic acid by RT-PCR and Met protein by Western analysis, and underwent phosphorylation of tyrosine residues on Met with HGF exposure. A Boyden chamber invasion assay using collagen type I showed that HGF caused a specific dose-response increase in trophoblast invasion first seen at 10 ng/mL (2.2-fold increase; P < 0.05). The stimulation of trophoblast invasion by HGF may in part be due to the 2-fold induction of 92-kDa collagenase as determined by zymogram analysis of the trophoblast-conditioned medium. These studies suggest that HGF has an important role in placental trophoblast invasion through the activation of Met and the subsequent induction of 92-kDa collagenase in these cells. In addition, decreased placental production of HGF in preeclampsia provides a potential mechanism for the lack of trophoblast invasion that is seen in this pregnancy disorder.

Hepatocyte growth factor (HGF) induces invasion of endometrial carcinoma cell lines in vitro.

OBJECTIVES: The overall goal of this study was to investigate the role of the hepatocyte growth factor (HGF)/Met pathway in the pathophysiology of invasive endometrial carcinoma. Our objectives were (1) to examine expression of HGF and Met in surgical endometrial carcinoma specimens and endometrial carcinoma cell lines, and (2) to determine if HGF would stimulate invasion of endometrial carcinoma cell lines in vitro. METHODS: Using RT-PCR and Western immunoblotting, endometrial carcinoma specimens and the endometrial carcinoma cell lines KLE, HEC-1A, HEC-1B, and RL-95 were examined for expression of HGF and Met. A Boyden chamber invasion assay using collagen type I coated 8-microm porous membranes was then used to determine if HGF would stimulate cell invasion. Last, we assessed the capacity of endometrial stromal cells, isolated from normal human endometrium, to produce HGF as determined by an enzyme-linked immunosorbent assay and to stimulate invasion of the KLE cell line. RESULTS: All of the endometrial carcinoma tissue samples were found to express Met mRNA, and two of four samples expressed HGF mRNA. However, the endometrial carcinoma cell lines expressed only Met and not HGF mRNA. Both the endometrial carcinoma tissue specimens and the endometrial carcinoma cell lines expressed the 140-kDa Met protein. HGF induced the invasion of the KLE and HEC-1A cells through the collagen-coated membranes in a dose-dependent fashion. The optimal concentration of HGF was between 10 and 100 ng/ml. HGF (10 ng/ml) stimulated KLE invasion 1.8-fold (P < 0.05) and HEC-1A invasion 6.5-fold (P < 0.05). During exposure to endometrial stromal cell conditioned medium containing HGF as determined by ELISA, invasion of the KLE cell line was stimulated 2.5-fold (P < 0.05). CONCLUSION: These results demonstrate that HGF stimulates the invasion of endometrial carcinoma cells in vitro. Since endometrial adenocarcinoma specimens express Met, these findings suggest that the HGF/Met pathway may play a role in the invasive progression of endometrial carcinoma.