The Role of Lymphovascular Space Invasion and Cytology in the Prognosis of Endometrial Cancer.

BACKGROUND: Lymphovascular space invasion (LVSI) and cytology are both independent and strong prognostic factors in endometrial cancer. This study aims to highlight the impact of LVSI and cytology positivity on prognosis, in addition to molecular classification. METHODS: A retrospective review was conducted on the records of 223 patients with endometrial cancer diagnosed between January 2011 and January 2021. The inclusion criteria stipulated that the patients were diagnosed with endometrial cancer by endometrial biopsy and were operated in the clinic. The exclusion criteria included sarcoma in the postoperative pathology report results or synchronous tumor. Staging was performed according to the Fédération internationale de gynécologie et d'obstétrique (FIGO) 2009 criteria. Cytology (using 50 cc saline) was obtained upon entry into the peritoneal cavity. In 20 patients, saline was not used due to the presence of ascites in the abdomen. The Kaplan-Meier method was employed to evaluate overall survival and progression-free survival. Survival rates were compared in terms of cytology and LVSI. RESULTS: After analyzing the postoperative pathology results, it was found that the mean tumor size was 4.03 ± 2.3 cm. The most common histological type was endometrioid carcinoma, with stage IA being the most common stage. Out of 223 patients with endometrial cancer, the overall survival rate was 82.4%, and the progression-free survival rate was 88.3%. For patients negative for LVSI, the progression-free survival rate was 93%, while for LVSI-positive patients, it was 77.3% (p < 0.001). Additionally, the progression-free survival rate for patients negative for cytology was 90.4%, whereas for cytology-positive patients, it was 77.1% (p < 0.05). CONCLUSIONS: In our study, we observed that LVSI positivity and cytology positivity also reduced the overall survival rate. We aimed to highlight that, in addition to molecular classification, cytology positivity and LVSI positivity are still highly significant and independent factors in prognosis.

The cytotoxic effects of indoleamine 2, 3-dioxygenase inhibitors on triple negative breast cancer cells upon tumor necrosis factor α stimulation.

Context: Overexpressed indoleamine 2,3-dioxygenase (IDO) has been observed in many types of cancer and plays an essential role in the tumor microenvironment through immune cells function. Aims: In our study, the therapeutic potentials of two different IDO inhibitors (Epacadostat [EPA] and 1-methyl-L-tryptophan [L-1MT]) in triple-negative breast cancer (TNBC) cells were assessed with and without tumor necrosis factor-α (TNF-α) stimulation. Materials and Methods: The anticancer activity of EPA and L-1MT alone and in combination with TNF-α was analyzed by WST-1, annexin V, cell cycle analysis, and acridine orange/ethidium bromide staining. In addition, the relationship between IDO1 and programmed death-ligand 1 (PD-L1) expressions in TNBC cells upon treatment with IDO inhibitors was evaluated by reverse transcription-polymerase chain reaction analysis. Statistical Analysis Used: SPSS 22.0 was conducted for statistical analysis. The one-way analysis of variance with Tukey's multiple comparison test was performed for multiple groups. Independent (unpaired) t -test was used for the comparison of two groups. Results: EPA and L-1MT alone significantly suppressed the TNBC cell viability through the induction of apoptotic cell death and G0/G1 arrest (P < 0.05). TNF-α alone induced the overexpression of IDO1 and PD-L1 in TNBC cells compared with MCF-10A control cells. However, IDO inhibitors significantly inhibited overexpressed IDO1 mRNA levels. Furthermore, EPA alone and co-treated with TNF-α suppressed the mRNA level of PD-L1 in TNBC cells. Therefore, TNF-α stimulation enhanced the therapeutic effects of IDO inhibitors on TNBC. Conclusions: Our findings showed that the efficacy of IDO inhibitors was mediated by pro-inflammatory cytokine. However, different molecular signaling pathways are associated with pro-inflammatory cytokines production, and the expression of IDO1 and PD-L1 calls for further investigations.

Relationship between molecular markers and lymphadenectomy and lymphovascular space invasion in endometrial cancer.

PURPOSE: Relationship between pathologic parameters, surgical parameters, or lymph node status with oncologic outcomes is not fully elucidated in endometrial cancer (EC). We want to investigate the molecular classification of uterine cancer in the Turkish population and its relationship between lymphadenectomy and lymph node metastasis. METHODS: In this study, 100 patients' clinical and pathologic data diagnosed with EC were analyzed. Pathologic and molecular parameters were investigated and compared them with clinical parameters. RESULTS: According to the molecular analysis, 16 patients (16%) had p53 mutation, 3 patients (3%) were classified as POLE mutant group, 38 (38%) patients in the MSI group, and the remaining 43 patients (43%) into the no specific mutation profile (NSMP) group. Lymph node metastasis rate was significantly higher in copy number high (CNH) group compared to the others. In the CNH group, 29 of 437 (6.6%) dissected lymph nodes had metastasis. The median OS was the highest in the POLE group (72 months) and lowest in the CNH group (36 months). CONCLUSION: Endometrial cancer patients showed significantly different overall and disease-free survival according to the molecular subtypes and it was consistent with the literature, Lymph node metastasis risk was the highest in CNH group. MSI status is important for the lymph node metastasis risk but not all abnormalities, especially PMS2 and MLH1 expression changes showed the highest risk.

The Anticancer Potential of Chlorine Dioxide in Small-Cell Lung Cancer Cells.

Background Chlorine dioxide (ClO2) is an effective disinfectant consisting of oxygen, chloride, and potassium. Because of its high oxidative capacity, ClO2 exerts antimicrobial, antiviral, and antifungal effects. However, its anticancer effects remain to be elucidated. Methodology The anticancer activity of CIO2 was assessed on DMS114 small-cell lung cancer (SCLC) cells and human umbilical vein endothelial cells (HUVEC) as control by WST-1, Annexin V, cell cycle analysis, and acridine orange staining. We for the first time investigated the possible therapeutic effects of long-term stabilized ClO2 solution (LTSCD). Results Our preliminary findings showed that LTSCD significantly inhibited the proliferation of SCLC cells (p < 0.01) with less toxicity in HUVEC cells. Additionally, LTSCD induced apoptotic cell death in SCLC cells through nuclear blebbing and vacuolar formation. However, LTSCD treatment did not induce cell cycle arrest in both cell lines. Conclusions LTSCD can be a therapeutic potential for the treatment of SCLC. However, further investigations are required to assess the LTSCD-induced cell death in SCLC both in vitro and in vivo.

Prognostic value of systemic inflammation response index in patients with persistent human papilloma virus infection.

OBJECTIVES: Persistent human papilloma virus (HPV) infection is a risk factor for the progression of cervical neoplasia into invasive carcinoma. Many inflammatory markers obtaining from hemogram parameters as platelets, monocytes, lymphocytes, and neutrophils or their ratios are still under investigation in recent decades, especially in the oncology era. Indeed, there have not been enough data about the relationship between these parameters and cervical cancer in the literature. Our primary aim was to investigate the possible relationship between the persistent HPV, which is one of the significant risk factors of cervical cancer, and these inflammatory markers. Further, we can add an easy follow-up parameter in women with persistent HPV infection. MATERIAL AND METHODS: The study included patients between 30-65 years old, tested positive for HPV, and afterward had an HPV control test between January 2015 and June 2020. RESULTS: The study included 114 HPV DNA-positive patients. The mean age was 43 (standard deviation 8.7), and 41 of them (36%) had persistent HPV, but the remaining 73 (64%) did not. The baseline neutrophil/lymphocyte ratio (NLR) value was 2.1, platelet/lymphocyte ratio (PLR) was 133, monocyte/lymphocyte ratio (MLR) was 0.28, and systemic inflammation response index (SIRI) was 0.9. All the parameters were significantly higher in the persistent HPV group compared to the non-persistent group. Patients who had 0.65 and under this had a significantly lower risk of persistent HPV. CONCLUSIONS: Persistent HPV disease can be predicted with an elevated SIRI, NLR, and other hematologic parameters. So, we can closely follow up with these patients with different algorithms to prevent cervical cancer.

Clinical implication of preoperative psoas muscle area in endometrial cancer patients.

OBJECTIVE: Obesity is a significant risk factor for endometrial cancer. In contrast, sarcopenia describes a loss of the body's muscle mass that is closely related to unfavorable clinical outcomes. Even endometrial cancer patients have high rates of obesity, and they should have a significantly higher risk for undiagnosed sarcopenia or fragile muscle quality. METHODS: This is a retrospective study that included an endometrial cancer database collected from a tertiary gynecologic cancer center. We investigated the relationship between preoperative psoas muscle area by magnetic resonance imaging, surgical outcomes and pathological features. RESULTS: The study included 116 patients, the mean height was 160 cm (Standart deviation 7), weight was 72 kg (Standart deviation 18), and the median duration of hospitalization was 4 days (Interquartile range 2-9) in the whole study group. Sarcopenia was diagnosed in 25 (21.6%) patients, according to the magnetic resonance imaging findings. Three (6.5%) obese patients had sarcopenia, but it was 31.4% in nonobese patients (p=0.026). The median duration of hospitalization was five days (3-9 days) in the sarcopenia group, and it was four days (2-7 days) in the non-sarcopenia group. CONCLUSION: Sarcopenic patients did not have increased surgical complication rates following uterine cancer surgery. We should be aware of hospitalization duration in those patients, and sarcopenic counterparts necessitate longer follow-up after the surgery.

Hematologic parameters as a predictor of myometrial and cervical invasion in endometrial cancer.

BACKGROUND: Despite significant improvements in molecular biology for uterine cancer, we did not have specific peripheral blood biomarkers for clinical usage such as prognostic or predictive outcomes of disease in the last decade. METHODS: A retrospective endometrial cancer database was collected from a tertiary gynecologic cancer center. The cohort included only endometrioid type uterine cancer. Subsequently, we investigated the relationship between preoperative hematologic parameters and pathologic findings. RESULTS: In this study, 191 non-metastatic endometrial cancer (median age was 61 years, ranging from 41 to 86 years) were analyzed. Lymphocyte-to-monocyte ratio (LMR) was significantly different between the FIGO stage I and II (4.48 vs. 3.88, P=0.004). Platelet-to-lymphocyte (PLR) was significantly higher in FIGO stage III than stage I, and LMR was significantly decreased by each FIGO stage. LMR values significantly decreased with a depth of myometrial invasion. PLR and eosinophil-to-lymphocyte ratio (ELR) values were significantly higher in patients with cervical invasion compared to those without invasion, 287 vs. 144, P=0.005, 10.3 vs. 6, P=0.022, respectively. CONCLUSIONS: This study revealed that low-LMR levels and high-PLR with ELR levels correlated with myometrial and cervical invasion, respectively. These findings can explain why hematologic parameters have an impact on oncologic outcomes.

Performing gynecologic cancer surgery during the COVID-19 pandemic in Turkey: A multicenter retrospective observational study.

OBJECTIVE: To report the perioperative outcomes of 200 patients with gynecologic cancer who underwent surgery during the Novel Coronavirus Disease (COVID-19) pandemic and the safety of surgical approach. METHODS: Data of patients operated between March 10 and May 20, 2020, were collected retrospectively. Data were statistically analyzed using IBM Statistical Package for the Social Sciences (SPSS) Statistics for Windows v. SP21.0. RESULTS: Data of 200 patients were included. Their mean age was 56 years. Of the patients, 54% (n=108), 27.5% (n=55), 12.5% (n=25), and 2% (n=4) were diagnosed as having endometrial, ovarian, cervical, and vulvar cancer, respectively. Of them, 98% underwent non-emergent surgery. A minimally invasive surgical approach was used in 18%. Stage 1 cancer was found in 68% of patients. Surgeons reported COVID-related changes in 10% of the cases. The rate of postoperative complications was 12%. Only two patients had cough and suspected pneumonic lesions on thoracic computed tomography postoperatively, but neither was positive for COVID-19 on polymerase chain reaction testing. CONCLUSION: Based on the present findings, it is thought that gynecologic cancer surgery should continue during the COVID-19 pandemic while adhering to the measures. Postponement or non-surgical management should only be considered in patients with documented infection. Gynecologic cancer surgery should continue during the COVID-19 pandemic while adhering to measures. Only 1% of patients developed COVID-19-related symptoms during the postoperative follow-up period.