Methods: Ascites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control). In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2(+) Tregs and TNFR2(-) Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC.
Results: High levels of immunosuppressive (sTNFR2, IL-10, and TGF-β) and pro-inflammatory cytokines (IL-6 and TNF) were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4(+)CD25(hi)FoxP3(+) Tregs, resulting in an increased TNFR2(+) Treg/effector T cell ratio. Furthermore, TNFR2(+) Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2(+) Treg frequency was inversely correlated with interferon-gamma (IFN-γ) production by effector T cells, and was uniquely able to suppress TNFR2(+) T effectors. Blockade of IL-6, but not TNF, within ascites decreased TNFR2(+) Treg frequency. Results indicating malignant ascites promotes TNFR2 expression, and increased suppressive Treg activity using PBMC were confirmed using purified Treg subsets.
Conclusion: IL-6 present in malignant ovarian cancer ascites promotes increased TNFR2 expression and frequency of highly suppressive Tregs.
METHODS: A total of 82 archived paraffin embedded HM tissues with subtypes classified based on H&E staining - 39 (47.5%) CHM, 41 (50.0%) PHM and two (2.43%) unclassified molar pregnancy were retrieved. All tissue samples were subjected for p57kip2 IHC analysis and HM subtypes were then reclassified.
RESULTS: A total of 66 cases (80.5%) were re-classified as CHM, 14 cases (17.1%) as PHM and two cases (2.4%) were decidual and cystic tissues. Analysis using p57kip2 immunostaining showed a diagnostic discrepancy of 33.0% from routine H&E staining and helps to improve the characterisation of the HM subtypes specifically at early gestations which have less distinctive morphologies.
CONCLUSIONS: IHC using p57kip2 monoclonal antibody should be considered as a routine ancillary test to H&E in improving the diagnosis of HM subtypes particularly in developing countries with limited resources.
METHODS: A cross-sectional study was conducted of 116 married women with gynaecological cancer who attended the gynaeoncology and oncology clinics at Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Sociodemographic and clinical data were collected. Sexual dysfunction was measured using the Malay Version Female Sexual Function Index (MVFSFI). Univariate and multivariate logistic regression analyses were used to determine the risk factors of female sexual dysfunction.
RESULTS: The prevalence of sexual dysfunction among gynaecological cancer survivors was 60% (70 out of 116). Sexual dissatisfaction was the most prevalent domain of sexual dysfunction at 68.1%. Sexual dysfunction was significantly associated with low education levels (Primary level, AOR = 4.92, 95% CI: 1.12-21.63; secondary level, AOR = 4.06, 95% CI: 1.14-14.44). Non-Malays were significantly more likely to have sexual dysfunction compared with Malays (AOR = 3.57, 95% CI: 1.16-11.06). In terms of treatment, combinations of surgery and radiotherapy (AOR = 4.66, 95% CI: 1.01-21.47) as well as surgery and chemoradiation (AOR = 5.77, 95% CI: 1.20-27.85) were considered.
CONCLUSIONS: Gynaecological cancer survivors with lower education levels, non-Malay ethnicity, and receiving treatment combinations of surgery and radiotherapy or surgery and chemoradiation have a higher risk of sexual dysfunction. A holistic approach in managing the various sociocultural and clinical issues is required to prevent sexual dysfunction among these patients.
METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.