OBJECTIVE:To evaluate the prognostic impact of primary surgery on patients with HPV-independent, advanced or metastatic endocervical adenocarcinoma (EAC) who typically exhibit poor survival outcomes and resistance to conventional therapies such as chemoradiotherapy. METHODS:A bi-institutional retrospective study was conducted at Samsung Medical Center and Taiwan National University Hospital. Between 2001 and 2023, 92 patients with HPV-independent advanced or metastatic EAC were included. Patients were divided into two groups: 54 (58.7%) underwent primary surgery and 38 (41.3%) received non-surgical treatments, including definitive radiotherapy or palliative chemotherapy. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) between groups. Multivariate analysis was performed to identify independent prognostic factors. RESULTS:The surgery group demonstrated significantly improved outcomes, with a median PFS of 19.2 months, compared with 10.0 months in the non-surgery group (P < 0.001). Median OS was not reached in the surgery group, whereas it was 24.1 months in the non-surgery group (P = 0.002). Multivariate analysis showed that non-surgical treatment was an independent predictor of poor PFS (hazard ratio [HR] 2.25; 95% confidence interval [CI] 1.18-4.29; P = 0.013) and OS (HR 3.25; 95% CI 1.37-7.73; P = 0.008). Additionally, the recurrence rate was significantly lower in the surgery group (55.6%) than in the non-surgery group (84.2%; P = 0.006). CONCLUSION:Primary surgery significantly improves survival outcomes in patients with HPV-independent advanced or metastatic EAC. These findings suggest that surgery should be considered as part of a multimodal treatment strategy for this aggressive subtype, highlighting the need for individualized therapeutic approaches beyond standard chemoradiotherapy protocols.

OBJECTIVE:In this study, we evaluated the role of prolonged progestin treatment on atypical endometrial hyperplasia (AEH) patients who did not achieve complete regression (CR) after at least 3 months of progestin treatment. Possible prognostic factors predicting disease regression and recurrence were also assessed. METHODS:We retrospectively identified patients who had histologically confirmed persistent disease after at least 3 months of progestin treatment at two tertiary centers in Korea and Taiwan. Clinicopathologic factors and clinical outcomes were obtained from medical records. Logistic regression was used to analyze the relationship between covariates and the probability of CR and relapse. RESULTS:Fifty-two patients were included. Thirty-seven of 52 patients (71.2%) achieved CR after prolonged progestin treatment. Median time from starting progestin treatment to CR was 12.0 months. Daily administration of medroxyprogesterone acetate ≥200 mg or megestrol acetate ≥80 mg was associated with higher probability of regression. Nineteen of 37 patients (51.4%) experienced recurrence, with median time from CR to relapse of 15.0 months. Body mass index ≥27 was associated with higher relapse probability. Twelve of 16 patients with disease progression to endometrial carcinoma underwent surgery. The 12 cases had stage I tumors and lived without disease. CONCLUSION:Extension of progestin treatment course is feasible for AEH patients without an initial response to progestin. Higher daily progestin dosage was associated with higher probability of CR, and obesity was associated with higher risk of relapse. The patients without an initial response to progestins and whose AEH progressed to endometrial carcinoma had good prognoses.

The therapeutic effect of para-aortic lymphadenectomy in patients with clinically pelvic node-positive but para-aortic node-negative endometrial cancer remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared with pelvic lymphadenectomy alone in these patients. We retrospectively reviewed patients with clinically FIGO stage IIIC1 high-grade endometrial cancer at two tertiary centers. Patients were stratified according to type of lymphadenectomy and subgroup analyses were performed. Kaplan–Meier analysis and a Cox proportional-hazards model were used to evaluate survival outcomes. A total of 56 patients were identified. Of these patients, 18 underwent pelvic lymphadenectomy alone, and 38 underwent combined pelvic and para-aortic lymphadenectomy. After staging surgery, 34 (60.7%) patients had pathologically confirmed lymph node metastases. Within a median follow-up of 57.5 months, there were no significant differences in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In subgroup analyses, the node- and lymphovascular space invasion (LVSI)-positive patients characterized by grade 3 endometrioid histologic type (p = 0.010) or negative peritoneal washing cytology (p = 0.035) had an RFS benefit from combined pelvic and para-aortic lymphadenectomy.

Background Expression of immune checkpoints in the tumor microenvironment is one mechanism underlying paclitaxel (PTX) chemoresistance. This study aimed to investigate whether the addition of checkpoint blockade to PTX can improve the therapeutic efficacy against apparently disseminated intraperitoneal tumors. Methods We analyzed the in vivo expression of various immune checkpoints in CD3 + CD8 + cytotoxic T cells from tumor-bearing mice treated with or without PTX and validated the tumor-killing activities of selected checkpoint-expressing T-cell subpopulations ex vivo. The regulation of selected checkpoints was investigated in vitro. The therapeutic effects of inhibition of a targeted checkpoint pathway with antibodies added to PTX therapy were examined. Results CD3 + CD8 + T cells expressed with herpes virus entry mediator (HVEM), programmed cell death 1 (PD-1), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3) in tumor-bearing hosts treated with PTX had effective tumoricidal activities. In addition to PTX and cytokines, B and T lymphocyte attenuator (BTLA) or homologous to lymphotoxin, exhibits inducible expression and competes with herpes simplex virus (HSV) glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT) interacting with HVEM can regulate the expression of PD-1 on CD3 + CD8 + T cells. Interleukin (IL)-15 increased the percentage of HVEM high granzyme B (GZMB) + cells among CD3 + CD8 + T cells, which was suppressed by the BTLA/HVEM signal. LIGHT induced the percentage of HVEM + GZMB + cells but not HVEM high GZMB + cells among CD3 + CD8 + T cells. Expression of IL-15, BTLA, or LIGHT was detected in CD19 + B cells and regulated by damage-associated molecular patterns/Toll-like receptor interactions. In the tumor-bearing hosts treated with PTX, certain proportions of BTLA + B or PD-1 + T lymphocytes were still noted. When dual inhibition of BTLA and PD-1 was added to PTX, the antitumor effects on intraperitoneally disseminated tumors can be significantly improved. Conclusions Dual blockade of BTLA on B cells and PD-1 on cytotoxic T cells may have clinical potential for enhancing the efficacy of PTX in the treatment of tumors with intraperitoneal spread, including epithelial ovarian carcinomas.

Background/Purpose: Efforts were made to explore the influence of diagnostic timing for cancer-associated thromboembolic events on survival of ovarian cancer patients. Methods: We reviewed the medical records of 75 ovarian cancer patients with thromboembolism and evaluated the prognostic factors affecting disease-free survival and overall survival. Results: These 75 patients were classified into two categories by the diagnostic timing of the thromboembolism, during (33 cases) and after (42 cases) initial diagnosis of ovarian cancer groups. The diagnostic timing of thromboembolism was not related to disease-free survival or overall survival of the studied population. Advanced disease stage, clear cell histology, interval debulking surgery, no recurrence/persistence of ovarian cancer, and patients treated with anticoagulant(s) treatment >3 months were associated with the disease-free survival. Advanced disease stage, clear cell histology, body mass index (BMI) >= 24 kg/m(2) at the diagnosis of ovarian cancer, and no recurrence/persistence of ovarian cancer influenced the overall survival. In the subgroup analysis, compared to the after initial ovarian cancer diagnosis group, patients with stage I/II disease, BMI <24 kg/m(2) at the diagnosis of ovarian cancer, or primary debulking surgery in the during cancer diagnosis group had longer disease-free survival, and overall survival benefit was observed in cases with stage I/II disease, or primary debulking surgery. Conclusion: The diagnostic timing of thromboembolism was not related to disease-free or overall survival of ovarian cancer patients, but associated with that of specific patient subgroups. Copyright (c) 2023, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background/purpose Vaginal delivery, compared with Cesarean delivery, remains a less chosen mode of delivery for twin pregnancy. We studied the maternal and perinatal outcomes of twin pregnancy with different modes of delivery. Methods A retrospective study with data collected from a regional hospital, including vital twin pregnancies delivered at gestational age of 32 weeks and above. Medical charts were reviewed for prenatal conditions and postpartum outcomes. Results Ninety-eight pairs of twins were included and 44.9% were delivered via vaginal delivery. Women in the vaginal delivery group were significantly younger (32.5 ±4.3 years versus 34.8 ±4.6 years, p < 0.01), multiparous (34.1% versus 18.5%) and with more twins in vertex-vertex presentation (70.5% versus 33.3%) compared with women in the Cesarean delivery group. There were no differences between maternal postpartum complications and neonatal outcomes in both groups. The outcomes showed longer inter-twin delivery time interval (5.7 ± 5.6 versus 1.5 ± 0.9 min, p < 0.01), less estimated blood loss (198.7 ± 144.1 versus 763.2 ± 332.3 mL, p < 0.01), and shorter maternal hospital stay (3.0 ± 0.5 versus 5.7 ± 0.5 days, p< 0.01) in the vaginal delivery group. Twenty newborns had Apgar score below seven at birth. Logistic regression analysis revealed that low Apgar score was independently related to younger maternal age, maternal obstetric diseases and fetal non-vertex presentation. Gestational weeks and mode of delivery were not related to low Apgar score. Conclusion With careful case selection, vaginal delivery could be safely performed in twin pregnancies with less estimated blood loss and better recovery than Cesarean delivery.

PURPOSE:The therapeutic effect of para-aortic lymphadenectomy in early-stage high-grade endometrial cancer remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared to pelvic lymphadenectomy alone in patients with pathologically diagnosed FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers. METHODS:We retrospectively reviewed the medical records of 281 patients with histologically confirmed FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers who underwent pelvic lymphadenectomy alone or combined pelvic and para-aortic lymphadenectomy in staging surgery at two tertiary centers in Korea and Taiwan. Prognostic factors to predict outcomes in these cases were also analyzed. RESULTS:Among 281 patients, 144 underwent pelvic lymphadenectomy alone and 137 underwent combined pelvic and para-aortic lymphadenectomy. Within a median follow-up of 45 months, there was no significant difference in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In multivariable analysis, age at diagnosis ≥60 years (HR = 2.20, 95% CI 1.25-3.87, p = 0.006) and positive lymph-vascular space invasion (LVSI) (HR = 2.79, 95% CI 1.60-4.85, p < 0.001) were associated with worse RFS, and only non-endometrioid histology was associated with worse OS (HR = 3.18, 95% CI 1.42-7.12, p = 0.005). In further subgroup analysis, beneficial effects of combined pelvic and para-aortic lymphadenectomy on RFS and OS were not observed. CONCLUSIONS:In this study, combined pelvic and para-aortic lymphadenectomy could not improve survival compared to pelvic lymphadenectomy alone in patients with FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers. Therefore, para-aortic lymphadenectomy may be omitted for these cases.