PREDICTIVE POWER OF OXIDATIVE STRESS BIOMARKERS IN RECURRENCE AND SURVIVAL IN ADVANCED CERVICAL CANCER.

The aim of our study was to measure the levels of 8-hydroxy-2-deoxyguanosine, malondialdehyde, and antioxidant enzymes in patients with locally advanced cervical cancer prior to treatment to determine how these evaluated biomarkers are associated with cervical cancer recurrence and to estimate their potential in further research and clinical use. MATERIALS AND METHODS: The study included 45 female patients with newly diagnosed advanced cervical cancer who underwent concomitant chemoradiotherapy. The blood and urine samples were collected prior to treatment, between December 2013 and April 2016, and subsequent laboratory analysis was performed. After the medium follow-up of 29 months, the patients were divided into 3 groups according to the time of disease recurrence. A statistical analysis was performed in order to evaluate the relationship between the previously measured biomarkers and recurrence. RESULTS: Taken individually, the parameters of oxidative stress did not reveal significant differences between the three groups in our study. Nevertheless, the catalase and glutathione S-transferase activities were the best predictors of the recurrence. Based on the activities of these two oxidative enzymes, it was possible to separate the group of patients without recurrence after follow-up from the other two groups of patients with recurrent disease. CONCLUSIONS: The parameters of oxidative stress have a certain predictive value on the outcome of patients with advanced cervical cancer after concomitant chemo-radiotherapy.

Association of Peritoneal Cytology with Other Prognostic Factors in Endometrial Cancer.

Purpose: It is still debatable whether surgical staging of endometrial cancer (EC) should include sampling of peritoneal cytology (PC) and for what purpose this should be done. The aim of our study was to determine the significance of peritoneal cytology in EC and its association with other histological and clinical parameters. Methods: This is a retrospective study that comprises of results from 357 patients with EC that were operated in our center in the previous nine years. Patients were divided into two groups: the first group with a positive and the second group with a negative PC. Results: Malignant cells were found in the peritoneal cytology of 23 patients (6.4%), while 334 patients (93.6%) had negative PC. There was no significant difference in patients' age between the two groups (p = 0.20). Peritoneal cytology was more prevalent in the non-endometrioid than the endometrioid subtype of EC (p = 0.00). There was a significant statistical difference (p = 0.00) in malignant PC in stages where cancer is confined to the uterus (International Federation of Gynecologists and Obstetricians (FIGO) stages I and II) compared with those where cancer has metastasized outside the uterus (stages III and IV). Most of the patients with malignant PC (69.6%) had high-grade disease (G3). Conclusion: Malignant peritoneal cytology is associated with other negative prognostic factors in endometrial cancer (histological grade, FIGO stage, and non-endometrioid histological subtypes). Based on these findings, we encourage sampling of peritoneal washing in all EC patients and consider it mandatory in patients with non-endometrioid subtype, high-grade histology, and in advanced FIGO stage.

HISTOPATHOLOGIC PARAMETERS OF POSITIVE LYMPH NODE PREDICTABILITY IN ENDOMETRIAL CANCER.

Endometrial cancer is the most common malignancy of the female reproductive tract. Lymph node metastases are an important prognostic factor in endometrial cancer. Several prognostic factors have been shown to correlate with lymph node metastasis, including depth of myometrial invasion, cervical infiltration, histologic grade of the tumor, tumor diameter, histology type, lymphovascular invasion, and positive peritoneal cytology. The aim of the study was to identify the histopathologic parameters that would indicate with greater certainty the possibility of metastases into lymph nodes, which would serve as a basis to assess whether patients should undergo lymphadenectomy or not. This retrospective study included patients with endometrial cancer having undergone surgery at the Oncology Institute of Vojvodina during the 2012-2018 period. The study included 120 patients having undergone hysterectomy with bilateral adnexectomy and pelvic lymphadenectomy. Among patients who had lymph node metastases, there were statistically significantly more patients (p<0.01) with endometrial cancer histologic type 2, depth of myometrial invasion greater than 50%, cervical stroma infiltration, lymphovascular invasion, and positive peritoneal cytology. In conclusion, histopathologic parameters such as type 2 endometrial cancer, myometrial invasion depth greater than 50%, cervical stroma infiltration, lymphovascular invasion and positive peritoneal cytology increased the likelihood of lymph node metastases. Tumor size (>2 cm), as well as histologic grade did not correlate with a higher incidence of lymph node metastases. In this study, both parametrial infiltration and the number of lymph nodes removed were found to have clinical relevance but not statistical significance.

Oxidative stress and its role in cancer.

Reactive oxygen species (ROS) can damage lipids, nucleic acids, and proteins, thereby altering their functions. When a balance between production of ROS and antioxidative defense is disturbed, state of oxidative stress occurs. Oxidative stress leads to many diseases. There are few biomarkers that are used for better understanding how oxidative stress is involved in cancer pathophysiology. This review focuses on 8-hidroxy-2-deoxyguanosine (8-OHdG) and antioxidative enzymes as biomarkers for measurement of oxidative stress in different types of cancer. This review also deals with the product of lipid peroxidation, malondialdehyde (MDA), and across a variety of cancers. To address this aim, analysis of studies of breast, prostate, lung, colon, cervical, ovarian, brain, bladder, renal, thyroid cancer, and chronic lymphocytic leukemia has been conducted. In general, levels of antioxidative enzymes are mostly lower in cancer patients, while 8-OHdG and MDA are higher. Further research is needed, with focus on correlation levels of these biomarkers and advancement of the disease. Moreover, all studies explored the idea of those biomarkers as a useful tool in determining the levels of oxidative stress. Some of the studies proposed their potential in defining the stage of tumor progression.

Histopathological correlation of cervical biopsy and tissue after excision in patients with precancerous lesions of the cervix.

INTRODUCTION: Cervical intraepithelial neoplasia (CIN) are precancerous lesion of cervix, with incidence of 1.6 per 1000 for CIN 1 lesion and 1.2 per 1000 for CIN 3 lesion in USA. According to IARC incidence is higher in less developed and developing countries. Taking into account the fact that the sensitivity, specificity and accuracy of Papanicolaou swab and colposcopy vary, the final diagnosis is made by colposcopically guided biopsy and by excisions of the cervix. AIM OF THE STUDY: Comparing the histopathological findings of cervical biopsy and definitive histopathological findings after cervical excision in precancerous lesions of the cervix in relation to the degree of lesion, age and institution, where the biopsy was performed. MATERIALS AND METHODS: The study was retrospective and was conducted on a group of patients who underwent some excision techniques on the cervix after obtaining a histological finding of the cervical biopsy. RESULTS: In a total sample of 168 patients, a correlation of histopathological analysis of biopsy material and excision techniques was observed in 62.5% (105/168). This correlation was statistically significant (χ2 = 5.333, df 1; p = 0.0209). The greater correlation of histopathological material of biopsies and final histopathological material after excisions were obtained in Oncology Institute of Vojvodina (OIV) without statistical significance. CONCLUSION: A statistically significant accuracy of biopsy was noted in examined group of patients.

Neoadjuvant chemotherapy in locally advanced cervical cancer in pregnancy-Review of the literature.

Cervical cancer is the third most common malignancy in pregnancy. Pregnancy does not have a detrimental effect on the survival of patients with cervical carcinoma. Management of cervical carcinoma in pregnancy depends on the stage of the disease, tumor size, nodal status, pathohistological characteristics of the tumor, the gestation of pregnancy, age and parity of patient and her motivation to preserve the pregnancy. In pregnant patients with the locally advanced cervical carcinoma (LACC) and strong desire to continue the pregnancy, the neoadjuvant chemotherapy (NACT) could be the option to preserve pregnancy while having cancer under the control. The goal of NACT in treatment of LACC in pregnancy is: 1. To treat, stabilize and prevent further dissemination of the disease until the term 2. To decrease the volume and extent of the tumor, making it more operable or radiosensitive after delivery 3. To effect on lymph node metastasis and distant micrometastasis during pregnancy Chemotherapy should not be applied during the organogenesis, before 10th, preferably 14th week of gestation. Administration of chemotherapy after the first trimester is not related tothe increased number of congenital malformations. If applied in the second or third trimester, chemotherapy is connected withfetal growth restriction, low birth weight, and preterm labor. Since data on safety and efficacy of NACT in LACC in pregnancy are still limited and based on a low level of evidence from 37 cases known so far, this treatment modality should remain experimental and reserved to highly motivated patients wishing to preserve the pregnancy.