Prevalence of Carcinogenic Genotypes of HPV-Infected Women in a Ten-Year Period (2014-2023) in Vojvodina, Serbia.

Background and Objectives: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. Materials and Methods: This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. Results: An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. Conclusions: This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries.

Metabolic dysregulation in obese women and the carcinogenesis of gynecological tumors: A review.

Obesity is a significant health issue associated with increased cancer risks, including gynecological malignancies. The worldwide rise in obesity rates is significantly impacting both cancer development and treatment outcomes. Adipose tissue plays a crucial role in metabolism, secreting various substances that can influence cancer formation. In obese individuals, dysfunctional adipose tissue can contribute to cancer development through inflammation, insulin resistance, hormonal changes, and abnormal cholesterol metabolism. Studies have shown a strong correlation between obesity and gynecological cancers, particularly endometrial and breast cancers. Obesity not only increases the risk of developing these cancers but is also associated with poorer outcomes. Additionally, obesity affects the perioperative management of gynecological cancers, requiring specialized care due to increased complications and resistance to therapy. Treatment strategies for managing metabolic dysregulation in patients with gynecological cancers include weight management, statin therapy, and insulin-sensitizing medications. Emerging studies suggest that interventions like intermittent fasting and caloric restriction may enhance the effectiveness of cancer treatments. Furthermore, targeting cholesterol metabolism, such as with statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, shows potential in cancer therapy. In conclusion, addressing metabolic issues, particularly obesity, is crucial in preventing and treating gynecological malignancies. Personalized approaches focusing on weight management and metabolic reprogramming may improve outcomes in these patients.

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.

Preliminary outcomes of five-year survival for ovarian malignancies in profiled Serbian Oncology Centre.

OBJECTIVE: The present study purposed to determine characteristics of ovarian carcinoma and to analyze predictors of survival in patients with ovarian carcinoma. METHOD: A retrospective cohort study was conducted including the patients with diagnosed ovarian carcinoma treated at the Clinic for Operative Oncology, Oncology Institute of Vojvodina in the period from January 2012 to December 2016. Seventy-two women with ovarian carcinoma were included in the analysis. The data about the histological type of tumor, disease stage, treatment, lymphatic infiltration, and surgical procedure were collected retrospectively, using the database of the institution where the research was conducted (BirPis 21 SRC Infonet DOO ‒ Information System Oncology Institute of Vojvodina). Descriptive statistics and multivariate analysis using Cox proportional hazards model were performed. RESULTS: The univariate Cox regression analysis identified histology, tumor grade, FIGO (International Federation of Gynecology and Obstetrics) stage, NACT (Neoadjuvant Chemotherapy), number of therapy cycles, type of surgery, and chemotherapy response as independent predictors of mortality. Finally, the type of tumor and chemotherapy response had an increased hazard ratio for mortality in the multivariate Cox regression model. Herewith, the percentage of high-grade, advanced-stage ovarian cancer patients with complete response to chemotherapy, absence of recurrent disease, and lymphovascular space invasion were significant predictors of survival in patients with ovarian carcinoma. CONCLUSIONS: Herein, emerging data regarding precision medicine and molecular-based personalized treatments are promising and will likely modify the way the authors provide multiple lines of treatments in the near future.

Programmed cell death-1 and its ligands: Current knowledge and possibilities in immunotherapy.

Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies.

E6/E7 mRNA Expression of the Most Prevalent High-Risk HPV Genotypes in Cervical Samples from Serbian Women.

Cervical cancer caused by persistent infection with HR HPV genotypes is the second leading cause of death in women aged 15 to 44 in Serbia. The expression of the E6 and E7 HPV oncogenes is considered as a promising biomarker in diagnosing high-grade squamous intraepithelial lesions (HSIL). This study aimed to evaluate HPV mRNA and DNA tests, compare the results according to the severity of the lesions, and assess the predictive potential for the diagnosis of HSIL. Cervical specimens were obtained at the Department of Gynecology, Community Health Centre Novi Sad, Serbia, and the Oncology Institute of Vojvodina, Serbia, during 2017-2021. The 365 samples were collected using the ThinPrep Pap test. The cytology slides were evaluated according to the Bethesda 2014 System. Using a real-time PCR test, HPV DNA was detected and genotyped, while the RT-PCR proved the presence of E6 and E7 mRNA. The most common genotypes in Serbian women are HPV 16, 31, 33, and 51. Oncogenic activity was demonstrated in 67% of HPV-positive women. A comparison of the HPV DNA and mRNA tests to assess the progression of cervical intraepithelial lesions indicated that higher specificity (89.1%) and positive predictive value (69.8-78.7%) were expressed by the E6/E7 mRNA test, while higher sensitivity was recorded when using the HPV DNA test (67.6-88%). The results determine the higher probability of detecting HPV infection by 7% provided by the mRNA test. The detected E6/E7 mRNA HR HPVs have a predictive potential in assessing the diagnosis of HSIL. The oncogenic activity of HPV 16 and age were the risk factors with the strongest predictive values for the development of HSIL.

Preliminary outcomes of five-year survival for ovarian malignancies in profiled Serbian Oncology Centre

Abstract Objective: The present study purposed to determine characteristics of ovarian carcinoma and to analyze predictors of survival in patients with ovarian carcinoma. Method: A retrospective cohort study was conducted including the patients with diagnosed ovarian carcinoma treated at the Clinic for Operative Oncology, Oncology Institute of Vojvodina in the period from January 2012 to December 2016. Seventy-two women with ovarian carcinoma were included in the analysis. The data about the histological type of tumor, disease stage, treatment, lymphatic infiltration, and surgical procedure were collected retrospectively, using the database of the institution where the research was conducted (BirPis 21 SRC Infonet DOO - Information System Oncology Institute of Vojvodina). Descriptive statistics and multivariate analysis using Cox proportional hazards model were performed. Results: The univariate Cox regression analysis identified histology, tumor grade, FIGO (International Federation of Gynecology and Obstetrics) stage, NACT (Neoadjuvant Chemotherapy), number of therapy cycles, type of surgery, and chemotherapy response as independent predictors of mortality. Finally, the type of tumor and chemotherapy response had an increased hazard ratio for mortality in the multivariate Cox regression model. Herewith, the percentage of high-grade, advanced-stage ovarian cancer patients with complete response to chemotherapy, absence of recurrent disease, and lymphovascular space invasion were significant predictors of survival in patients with ovarian carcinoma. Conclusions: Herein, emerging data regarding precision medicine and molecular-based personalized treatments are promising and will likely modify the way the authors provide multiple lines of treatments in the near future.

Programmed cell death-1 and its ligands: Current knowledge and possibilities in immunotherapy

Abstract Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies.

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.

Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome.

BACKGROUND: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome. METHODS: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome. FINDINGS: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters. INTERPRETATION: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.

Germline mutations in cancer susceptibility genes in high grade serous ovarian cancer in Serbia.

Clinical criteria for genetic testing of genes other than BRCA1/2 in epithelial ovarian cancer (EOC) still do not exist. We assessed the frequency and predictors of deleterious mutations in 19 cancer predisposition genes in high-grade serous ovarian cancer (HGSOC) in Serbia. Next-generation sequencing was used to identify germline mutations in the whole coding regions of a gene panel. Patients' characteristics and sequencing data were summarized with descriptive statistics and compared using chi-square test. Among 131 HGSOC patients, 23 had BRCA1 (17.6%) while 5 had BRCA2 (3.8%) mutation. In addition, 9 (6.9%) pathogenic mutations were detected in other genes including BRIP1 (n = 2;1.5%), CHEK2 (n = 2;1.5%), NBN (n = 3;2.3%) and RAD51C (n = 2;1.5%). Factors that predicted for BRCA1/2 mutations were: breast and ovarian cancers in the same patient (p = 0.031), young age of EOC (p = 0.029), menstrual status (p = 0.004) and family history of cancer (p < 0.0001). However, these factors did not predict for mutations in other cancer susceptibility genes. Applying established referral criteria for genetic testing in Serbia will help identify BRCA1/2 mutation carriers but will not help identify mutations in other cancer susceptibility genes. Until better predictors emerge we should be performing wider genetic testing of EOC in order to identify all mutation carriers.

Lipid Peroxidation, Antioxidative Defense and Level of 8-hydroxy-2-deoxyguanosine in Cervical Cancer Patients.

BACKGROUND: Oxidative stress has been associated with cervical cancer. Our aim was to examine lipid peroxidation and the extent of oxidative stress in women diagnosed with different stages of cervical cancer in order to evaluate its potential role in the evolution of cancer. METHODS: We measured the concentration of thiobarbituric acid reactive substances, activities of antioxidative enzymes and 8-hydroxy-2-deoxyguanosine in 153 subjects. Enzymatic activity as well as TBARS concentration were measured spectrophotometrically, while 8-OHdG was determined by gas chromatography-mass spectrometry. PPatients were categorized: group II H-SIL; group III FIGO Ia-Ib and group IV FIGO IIa-IV. RESULTS: Our results showed highly significant increase in the level of lipid peroxidation in group IV when com pared to the control group, group II and group III (p<0.001). Activity of superoxide dismutase was also significantly higher in group IV when compared to control group (p<0.01), group II (p<0.01) and group III (p<0.05). Activity of catalase was also significantly higher in group IV when compared to control group (p<0.005), group II (p<0.005) and group III (p<0.05). Activity of glutathione-S-transferase was also significantly higher in group IV when compared to control group (p<0.05), group II (p<0.05) and group III (p<0.05). Activities of glutathione peroxidase and glutathione reductase showed no significant differences among the groups. Level of 8-OHdG was significantly higher in group IV than in the other groups (p<0.01). CONCLUSIONS: It can be concluded that oxidative stress is possibly involved in the pathogenesis of cervical cancer, demonstrated by increased lipid peroxidation and an altered antioxidant defense system and higher levels of 8-OHdG.

Thoracic Epidural Versus Intravenous Patient-Controlled Analgesia after Open Colorectal Cancer Surgery.

The aim of the study was to compare thoracic epidural analgesia (TEA) and intravenous patient-controlled analgesia (IV-PCA) after open colorectal cancer surgery. This prospective study included sixty patients scheduled for elective open colorectal surgery and randomized to either postoperative IV-PCA with morphine (n=30) or TEA with a mixture of levobupivacaine, fentanyl and adrenaline (n=30). Th e primary outcome was return of bowel function. The secondary outcome was quality of postoperative analgesia at rest, on coughing and during mobilization. Intermediate outcomes included patient satisfaction, time out of bed, rate of side effects and postoperative complications, and time of discharge. Recovery of postoperative ileus occurred sooner (p<0.001) and resumption of dietary intake was achieved earlier (p<0.001) in TEA group. Intensity of pain during the first 3 postoperative days was significantly lower at rest, on coughing and during mobilization (p<0.001), and mobilization was much more effi cient (p<0.005) in TEA than in IV-PCA group. Satisfaction scores were better in TEA group (p<0.001). Nausea, sedation and postoperative delirium occurred less frequently in TEA group (p<0.05, p<0.001 and p<0.05, respectively). TEA demonstrated significantly better effectiveness than IV-PCA after open colorectal cancer surgery and had a positive impact on bowel function, dietary intake, patient satisfaction and early mobilization. The results of this study demonstrated the importance of implementation of TEA as a preferred method for postoperative pain control after major open colorectal surgery.

Tissue expression of VEGF in cervical intraepithelial neoplasia and cervical cancer.

PURPOSE: To examine the expression of vascular endothelial growth factor (VEGF) in the cervical tissue of individuals divided into the control group (normal cervix), group A (HSIL lesions), and group B (cervical cancer, FIGO stage I-IIA). Analyzed was also the expression of VEGF between groups and subgroups in group A and B. The expression of VEGF was also compared with histopathological parameters in group B. METHODS: Examined was the histopathological material taken from 109 operated patients. The patients were divided into 3 groups based on the definitive histopathological findings: control group (30 patients), group A (33 patients), and group B (46 patients). Immunohistochemistry was performed to examine the expression of VEGF. RESULTS: The expression of VEGF was negative in the control group, while in 11 patients (33.33%) from group A and 28 patients (60.87%) from group B it was significantly different (p<0.05) compared to the control group. There was neither statistically significant difference in the expression of VEGF in group A regarding the type of intraepithelial lesion, nor in group B regarding the FIGO disease stage (p>0.05). In patients with poor histopathological prognostic parameters such as tumor diameter ≥ 2 cm (24/46), depth of stromal invasion ≥ 10 mm (32/46), positive lymph nodes (17/46), and with infiltration of the uterine body (11/46) a statistically significant difference was confirmed regarding the expression of VEGF. CONCLUSION: The increased VEGF expression in groups A and B compared with the control group indicated the importance of VEGF as a proangiogenic factor in neoangiogenesis in precancerous and cancerous changes in the cervix. The frequent expression of VEGF in the subgroup of patients with poor histopathological prognostic factors (group B) indicated the importance of the activity of proangiogenic factors in the process of cervical cancer neoangiogenesis. Further investigations should be aimed at these markers as prognostic factors in the high risk group of patients with cervical cancer who should receive adjuvant therapy after radical operation and consider using antiangiogenic drugs as part of adjuvant treatment.

Cyclooxygenase-2 expression in cervical cancer.

BACKGROUND/AIM: Cyclooxygenase (COX) or prostaglandin H2 synthase is the first enzyme that catalyzes the first two steps in the biosynthesis of prostaglandins from arachidonic acid. The aim of the study was to determine the expression level of COX-2 in patients with cervical cancer and compare it with that in the control group with no cervical pathology. METHODS: The study included 76 patients divided into two groups: the control group--30 patients without histopathological changes and the group A--46 patients with cervical cancer, FIGO stage IB-IIA. Histopathological and immunohistochemical analyses were performed in these two groups of patients. RESULTS: In the control group, the expression of COX-2 was not confirmed compared to the group A of 26 (56.52%) patients. The expression of COX-2 showed a statistically significant difference in the presence oflymphocytic stromal infiltration (p = 0.0053). The expression of COX-2 was more pronounced in the stromal tissue without lymphocytic infiltration (80% vs. 20%). CONCLUSION: A higher expression of COX-2 in cervical carcinoma without stromal lymphocytic infiltration suggests a possible paradoxical effect of COX-2 in immunosuppression. Frequent COX-2 expression in the subgroup with poor prognostic histological parameters in the group A indicates the importance of COX-2 expression in the carcinogenesis of cervical cancer.