Identifying the palliative care needs of patients and families in gynecologic surgical oncology: A scoping review.

Introduction: Patients undergoing oncology-related gynecologic surgical procedures experience substantial symptom burden and distress. Support from specialist palliative care teams may benefit these patients and their families; however, an evidence-informed approach to the integration of palliative care and gynecologic surgical oncology is needed. To inform such an approach, a scoping review synthesizing current evidence on the palliative care needs of patients and families in gynecologic surgical oncology was conducted.Methods: Reviewers performed a structured search of online databases CINAHL, Scopus, PsycINFO, MEDLINE, and PubMed in addition to the grey literature to identify relevant studies published between 2011 and June 11th, 2021. The original search identified 993 articles, which were dually screened for study inclusion, resulting in a final sample of articles from which data were systematically extracted and synthesized.Results: This review of 59 publications predominantly consisted of European studies (n = 26, 44.1%), described quantitative study methods (n = 47, 79.6%), followed an observational study design (n = 49, 83.1%), and focused on psychological impact of treatment as a major topic of study (n = 21, 35.6%). The dataset also described sexual function of women post treatment (n = 15, 25.4%), quality of life (n = 10, 16.9%), therapeutic decision making (n = 9, 15.2%), pain assessment (n = 2, n = 3.6%), and medication for symptom management (n = 2, 3.6%). Explicit discussion of specialist palliative care involvement was rare.Conclusion: The needs of patients and families in gynecologic surgical oncology are well-suited to palliative care collaboration; however, the body of literature on palliative care services provided to this unique population is underdeveloped.

Tubal ligation frequency in Oklahoma women with cervical cancer.

OBJECTIVE: Infrequent Pap screening is an important risk factor for cervical cancer. We studied the association between contraceptive methods, screening frequency, and cancer. METHODS: Women (n=2004) enrolled in the cross-sectional Study to Understand Cervical Cancer Endpoints and Determinants (SUCCEED) underwent colposcopy to evaluate an abnormal Pap test. Questionnaire data were compared between those with cervical intraepithelial neoplasia (CIN) 3/adenocarcinoma in situ (AIS) and those with invasive cancer to identify factors associated with cancer. Logistic regression was used to calculate age-stratified measures of association between contraceptive method and Pap frequency as well as tubal ligation (TL) and cancer risk. RESULTS: In all age groups, women with TL were more likely to have had no Pap screening in the previous 5 years compared to women using other contraception: 26-35 years (OR 4.6, 95% CI 2.4-8.6; p<0.001), 36-45 years (OR 3.8, 95% CI 2.1-7.0; p<0.001), and 46-55 years (OR 2.2, 95% CI 1.0-4.9; p=0.050). Subjects with cancer (n=163) were more likely to have had a TL (41% vs. 21%, p<0.001) than those with CIN 3/AIS (n=370). Age-stratified analyses showed increased odds of tubal ligation in women with cancer versus those with CIN 3/AIS between 25 and 45 years, with a significant increase in women 26 to 35 years old (OR 3.3, 95% CI 1.4-8.1; p=0.009). Adjusting for Pap frequency changed the effect only slightly, suggesting that increased risk was not fully mediated by lack of screening. CONCLUSION: Contraceptive type is associated with Pap screening. Women with TLs obtain less frequent Pap testing and may be at an increased risk for cervical cancer.

An updated clinicopathologic study of early-stage uterine papillary serous carcinoma (UPSC).

OBJECTIVES: Stage I-II uterine papillary serous carcinoma (UPSC) patients have a significant risk for extrapelvic recurrence. However, clinicopathologic risk factors for recurrence are not well understood. This study was undertaken to define the prognostic factors for recurrence and survival in patients with early-stage UPSC. METHODS: A retrospective, multi-institution analysis of surgically staged I-II UPSC patients was performed. Patients were treated by various adjuvant modalities. Age, race, sub-stage, percentage UPSC histology, lymphvascular space invasion (LVSI), tumor size and adjuvant treatment modality were evaluated for their effect on recurrence and survival outcomes. RESULTS: We identified 206 patients. Forty patients (19.4%) had 5-49% UPSC, 55 (26.7%) had 50-99% and 111 patients (53.9%) had 100% UPSC in their respective uterine specimens. Twenty one percent of patients experienced a primary recurrence. On univariate analysis, age, increasing %UPSC, LVSI, and tumor size were not significantly associated with recurrence or progression-free survival (PFS). However, substage (p=0.005) and treatment with platinum/taxane-based chemotherapy (p=0.001) were associated with recurrence/PFS. On multivariate analysis, only chemotherapy (p=0.01) was a significant factor affecting PFS, whereas age (p=0.05), substage (p=0.05), and chemotherapy (p=0.02) were associated with overall survival. CONCLUSIONS: Traditional risk factors for recurrence and survival in patients with early-stage endometrial cancer may not be relevant in patients with UPSC. Patients with any percentage UPSC in their uterine specimens are at a significant risk for recurrence and poor survival outcomes. Given that current clinicopathologic data does not accurately identify women most likely to benefit from adjuvant therapy, alternative prognostic markers based on novel techniques should be explored.

Docosahexaenoic acid inhibits superoxide dismutase 1 gene transcription in human cancer cells: the involvement of peroxisome proliferator-activated receptor alpha and hypoxia-inducible factor-2alpha signaling.

Docosahexaenoic acid (DHA; n-3, 22:6) is known to have anticancer activity, but its mechanisms of action remain to be further elucidated. We recently demonstrated that DHA down-regulates superoxide dismutase (SOD) 1 gene expression, thereby weakening cellular antioxidant forces and enhancing cytotoxicity in various human cancer cells. The objective of this study was to investigate the mechanism of the inhibitory effect of DHA on SOD-1 gene expression in human cancer cells. A reporter gene assay indicated that DHA suppresses SOD-1 gene transcription in a time- and concentration-dependent manner in human cancer cells. Pretreatment with vitamin E did not block the inhibitory effect of DHA, indicating that this suppression does not depend on lipid peroxidation. The suppressive effect of DHA on SOD-1 gene transcription could be mimicked by the peroxisome proliferator-activator receptor (PPAR) alpha ligand clofibrate but not the PPARgamma ligand troglitazone, suggesting the involvement of PPARalpha signaling. Deletion analysis of the key DNA binding elements in the SOD-1 gene promoter identified the distal hypoxia response element (HRE), but not the peroxisome proliferator response element or nuclear factor-kappaB element, as essential for the suppressive effects of DHA. Coimmunoprecipitation confirmed that PPARalpha, but not PPARgamma, forms a complex with hypoxia-inducible factor (HIF)-2alpha in cancer cells. Chromatin immunoprecipitation analysis indicated that both DHA and clofibrate reduce HIF-2alpha binding to the HRE. Thus, we have identified the distal HRE in the SOD-1 gene promoter that mediates the suppression on the transcription of this gene by DHA, and we have demonstrated the involvement of PPARalpha and HIF-2alpha signaling in this event.

PPARalpha signaling mediates the synergistic cytotoxicity of clioquinol and docosahexaenoic acid in human cancer cells.

This study investigated the involvement of PPARgamma and PPARalpha signaling in the synergistic anticancer activity of clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) and docosahexaenoic acid (DHA) in human cancer cells. The synergistic cytotoxicity of DHA and clioquinol was demonstrated in nine human cancer cell lines representing different tissues of origin. A2780, a well-established ovarian cancer model system, was chosen for further characterization because of its sensitivity to DHA and clioquinol. Both PPARalpha and PPARgamma were expressed in A2780 cells when analyzed with western blotting and reporter gene technique. Treatment of the cells with clofibrate (a PPARalpha agonist) and clioquinol for three days mimicked the synergy of DHA and clioquinol, whereas this synergy could not be seen with the use of troglitazone (a PPARgamma agonist) and clioquinol, suggesting that PPARalpha signaling is involved in the synergistic action. When used alone, the IC50 of clofibrate was 513 microM in A2780 cells. However, the addition of 5 microM clioquinol to clofibrate-treated cells led to a dramatic reduction of its IC50 value (148 microM). The combination effects index (CI) analysis confirmed the synergy of clioquinol and clofibrate on inhibiting cancer cell viability. Using inhibitors to block PPARalpha signaling diminished the synergistic cytotoxicity of clioquinol and DHA. These results provide pharmacological evidence that the synergistic anticancer action of clioquinol and DHA is mediated by PPARalpha signaling in human cancer cells.