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.

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.

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.

Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists.

BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.

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.

Polymorphic expression of glutathione transferases A1, M1, P1 and T1 in epithelial ovarian cancer: a Serbian case-control study.

PURPOSE: Since several studies have proposed that epithelial ovarian cancer should not be considered as a single disease entity and that it results from an accumulation of genetic changes, we aimed to assess the polymorphic expression of major cytosolic glutathione S-transferases (GSTM1, T1, A1 and P1) with respect to ovarian cancer susceptibility and aggressiveness. METHODS: This case-control study was conducted on 93 newly diagnosed epithelial ovarian cancer patients and 178 healthy matched controls. The multiplex polymerase chain reaction (PCR) was used to detect homozygous deletions of GSTM1 and GSTT1 genes. Analysis of the single nucleotide polymorphism (SNP) GSTA1 C69T was performed using PCR-restriction fragment length polymorphism (RFLP), while for SNP GSTP1 Ile105Val real-time PCR was used. RESULTS: No significant association to ovarian cancer risk was found for individual GSTM1, GSTA1 and GSTP1 genotypes (p>0.05). However, the carriers of GSTT1-active genotype were at 2-fold higher risk of ovarian cancer development (95%CI: 1.00-4.01, p=0.049), which was even more elevated in the subgroup of patients with positive family history of cancer. Moreover, the frequency of all three GST genotypes that might be associated to ovarian cancer risk (GSTT1-active, GSTA1-active and GSTP1-referent) was significantly higher in patients than in the control group (p=0.042). Even more, patients who were carriers of combination of these three genotypes represented over 64% of the total number of patients within any of the International Federation of Gynecology and Obstetrics (FIGO) stages of ovarian cancer. CONCLUSIONS: This study provides supportive evidence that GSTs might affect both susceptibility and progression of ovarian cancer.