Search

Byline: Joze Valentincic, D. Kuser, S. Smrkolj, Oki Blatnik, Mihael Junkar To achieve high removal rate and low electrode wear when roughing by the sinking electrical discharge machining process (EDM), appropriate average surface power density is required in the gap between the workpiece and the electrode. Since machining surface varies with the depth of machining, the rough machining parameters have to be selected on-line to obtain appropriate average surface power density in the gap. In this paper, a system for on-line selection of the machining parameters according to the given machining surface is presented. The selection of the machining parameters is based on the acquisition of only one process attribute, i.e. the percentage of short-circuit discharges, which is significant improvement comparing to known systems.

Background: High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS)., Patients and Methods: Forty-seven patients with primary HGSC and ascites were included. Flow-cytometric analysis was performed to detect percentages of CD3 + T cells (CD4 + , CD8 + , Tregs, and NKT cells), B cells, NK cells (CD56 bright CD16 - and CD56 dim CD16 + subsets), macrophages and dendritic cells (DCs). Furthermore, CD103 expression was analyzed on T cells and their subsets, while PD-1 and PD-L1 expression on all ICs. Cut-off of low and high percentages of ICs was determined by the median of variables, and correlation with PFS and OS was calculated., Results: CD3 + cells were the predominant ICs (median 51%), while the presence of other ICs was much lower (median ≤10%). CD103 + expression was mostly present on CD8 + , and not CD4 + cells. PD-1 was mainly expressed on CD3 + T cells (median 20%), lower expression was observed on other ICs (median ≤10%). PD-L1 expression was not detected. High percentages of CD103 + CD3 + T cells, PD-1 + Tregs, CD56 bright CD16 - NK cells, and DCs correlated with prolonged PFS and OS, while high percentages of CD8 + cells, macrophages, and PD-1 + CD56 bright CD16 - NK cells, along with low percentages of CD4 + cells, correlated with better OS only. DCs were the only independent prognostic marker among all ICs., Conclusions: Our results highlight the potential of ascites tumor-immune microenvironment to provide additional prognostic information for HGSC patients. However, a larger patient cohort and longer follow-up are needed to confirm our findings., (© 2023 Simona Miceska et al., published by Sciendo.)

A population of small stem cells with diameters of up to 5 μm resembling very small embryonic-like stem cells (VSELs) were sorted from human embryonic stem cell (hESC) cultures using magnetic-activated cell sorting (MACS) based on the expression of a stem-cell-related marker prominin-1 (CD133). These VSEL-like stem cells had nuclei that almost filled the whole cell volume and expressed stem-cell-related markers (CD133, SSEA-4) and markers of germinal lineage (DDX4/VASA, PRDM14). They were comparable to similar populations of small stem cells sorted from cell cultures of normal ovaries and were the predominant cells in ascites of recurrent ovarian cancer. The sorted populations of CD133+ VSEL-like stem cells were quiescent in vitro, except for ascites, and were highly activated after exposure to valproic acid and follicle-stimulating hormone (FSH), indicating a new tool to study these cells in vitro. These VSEL-like stem cells spontaneously formed clusters resembling tumour-like structures or grew into larger, oocyte-like cells and were differentiated in vitro into adipogenic, osteogenic and neural lineages after sorting. We propose the population of VSEL-like stem cells from hESC cultures as potential original embryonic stem cells, which are present in the human embryo, persist in adult human ovaries from the embryonic period of life and are involved in cancer manifestation.

Background: The mechanism of aggressive character of ovarian cancer and unsuccessful treatment of women with this deadly disease has been recently explained by the theory of cancer stem cells (CSCs). It has been reported that ovarian carcinogenesis and progression of disease is associated with epithelial-mesenchymal transition (EMT). EMT, a physiological cell process during embryonic development and later in life during regeneration, could, when induced in pathological condition, generate CSCs-like cells. Until now EMT in the ovarian tissue has been mainly studied in cell cultures in vitro. The aim of this study was to focus on in situ morphological changes in the ovarian surface epithelium of tumor tissue in women with epithelial ovarian cancer after we applied the antibodies for markers of EMT vimentin and pluripotency-related markers NANOG, SOX2 and SSEA-4., Methods: We analyzed ovarian tissue sections of 20 women with high grade serous ovarian carcinoma. After eosin and hematoxylin staining, used in standard practice, immunohistochemistry was performed for vimentin and markers of pluripotency: NANOG, SSEA-4 and SOX2. We focused on the ovarian surface epithelium in order to observe morphological changes in tumor tissue., Results: Among epithelial cells of the ovarian surface epithelium in women with serous ovarian carcinoma we observed a population of small NANOG-positive cells with diameters of up to 5 μm and nuclei, which filled almost the entire cell volumes. These small NANOG-positive cells were in some cases concentrated in the regions with morphologically changed epithelial cells. In these regions, a population of bigger round cells with diameters of 10-15 μm with large nuclei, and positively stained for vimentin, NANOG and other markers of pluripotnecy, were released from the surface epithelium. These cells are proposed as CSCs, and possibly originate from small stem cells among epithelial cells. They formed typical cell clusters, invaded the tissue by changing their round shape into a mesenchymal-like phenotype, and contributed to the manifestation of ovarian cancer., Conclusions: Our findings show morphological changes in the ovarian surface epithelium in tumor slides of high grade serous ovarian carcinoma and provide a new population of putative CSCs.

Background: The incidence of cervical cancer (CC) in Slovenia in 2011 was 13.2 per 100,000 women. The treatment of early stages of invasive cervical carcinoma involves several surgical techniques. In this article the authors would like to present a new combination of two methods which help to preserve fertility and to improve pregnancy outcome. The first procedure, radical vaginal trachelectomy (RVT), begins with laparoscopic pelvic lymphadenectomy. All suspicious lymph nodes are sent to frozen section. If those lymph nodes are negative, the procedure continues vaginally. Almost the entire cervix is removed with parametria and vaginal cuff. Permanent cerclage stitch is applied and covered with vagina on what is left of uterus. Second procedure, laparoscopic abdominal cerclage (LAC), begins with pneumoperitoneum. Mersilene tape is introduced in the abdominal cavity and placed through the visceral peritoneum at the isthmic part of the uterus with a Berci's needle. It is knotted and remains permanently., Materials and Methods: For the first procedure all the patients with confirmed cervical carcinoma (FIGO Stage IA₁, IA₂, and IB₁) and with the desire for fertility were recruited. For the second procedure, all the patients after RVT and after miscarriage after 14th week of gestation were recruited., Results: RVT was performed in 15 patients and laparoscopic abdominal cerclage in three of them (21.5%). All three patients achieved pregnancies and after 36th weeks of gestation delivered by cesarean section (100%)., Conclusions: RVT alone is an indication for LAC. Considering its success, LAC should be performed before any miscarriage.

Background: In previous studies it has been found that in cell cultures of human adult ovaries there is a population of small stem cells with diameters of 2-4 μm, which are present mainly in the ovarian surface epithelium and are comparable to very small embryonic-like stem cells (VSELs) from bone marrow. These cells are not observed by histopathologists in the ovarian tissue due to their small size and unknown clinical significance. Because these cells express a degree of pluripotency, they might be involved in the manifestation of ovarian cancer. Therefore we studied the ovarian tissue sections in women with borderline ovarian cancer and serous ovarian carcinoma to perhaps identify the small putative stem cells in situ., Methods: In 27 women with borderline ovarian cancer and 20 women with high-grade serous ovarian carcinoma the ovarian tissue sections were stained, per standard practice, with eosin and hematoxylin staining and on NANOG, SSEA-4 and SOX2 markers, related to pluripotency, using immunohistochemistry. We focused on the presence and localization of small putative stem cells with diameters of up to 5 μm and with the nuclei spread over nearly the full cell volume., Results: In ovarian sections of both borderline ovarian cancer and serous ovarian carcinoma patients we were able to identify the presence of small round cells complying with the above criteria. Some of these small cells were NANOG-positive, were located among epithelial cells in the ovarian surface epithelium and as a single cell or groups of cells/clusters in typical "chambers", were found only in the presence of ovarian cancer and not in healthy ovaries and are comparable to those in fetal ovaries. We envision that these small cells could be related to NANOG-positive tumor-like structures and oocyte-like cells in similar "chambers" found in sections of cancerous ovaries, which could support their stemness and pluripotency. Further immunohistochemistry revealed a similar population of SSEA-4 and SOX2-positive cells., Conclusions: We may conclude that putative small stem cells expressing markers, related to pluripotency, are present in the ovarian tissue sections of women with borderline ovarian cancer and high-grade serous ovarian carcinoma thus indicating their potential involvement in ovarian cancer.

Ovarian cancer is among the most common gynecologic cancers and unfortunately the most common cause of death from gynecologic malignancies. Due to few early symptoms and insufficient screening programs, an early diagnosis of ovarian cancer is very difficult and new biomarkers related to early ovarian carcinogenesis are needed. In the last years a growing scientific knowledge about cancer stem cells and their markers opened a new perspective on screening and early diagnosis of ovarian cancer. The transcription factor NANOG is not only a pluripotency and cancer stem cell-related marker, but also promotes cancer stem cell-like characteristics of tumor, tumor growth, dissemination, immune evasion, and resistance to conventional therapy. The recent data showed that small stem cells resembling very small embryonic-like stem cells are present in the ovarian surface epithelium of adult human ovaries. These cells expressed several genes related to primordial germ cells, germinal lineage, and pluripotency, including NANOG, therefore their involvement in the manifestation of ovarian cancer are not excluded. As majority of cancer cells within a tumor are non tumorigenic, the therapies targeting these cells cause tumor regression, but the survived cancer stem cells regenerate the tumor, so tumor relapse or reoccur. The eradication of cancer actually requires the elimination of cancer stem cells, therefore new strategies in treatment that specifically target cancer stem cells are urgently needed. Although the therapeutic efficacy of targeting NANOG as a cancer treatment method is still in experimental phase, the gene therapy with small interfering RNA or short hairpin RNA have already shown some promising therapeutic potential. The authors can conclude that NANOG represents a promising diagnostic marker and agent for target therapy of ovarian cancer.

Background: The objective of this analysis was to present the clinical outcome of patients with microinvasive adenocarcinoma (AC) of the uterine cervix treated at the Department of Obstetrics and Gynecology between 1999 and 2010., Materials and Methods: The authors analysed 125 patients with microinvasive AC. The analysis involved the following parameters: women's age at surgery, type of surgery, number of positive lymph nodes, and patient's survival. Additionally, a questionnaire regarding history and symptoms before diagnosis and postoperative follow-up was developed and analysed specifically for this study., Results: The mean women's age at surgery was 40.58 +/- 9.58 years. In 70 women (56%), the performed treatment was conization, 34 women (27.2%) underwent simple hysterectomy, and 24 (19.2%) women had radical hysterectomy. In 14 (11.2%) women, the margins of the cone were not disease-free, in nine of them the authors later performed radical hysterectomy. From 14 women who became pregnant after treatment, 13 (16.9%) of them gave birth. One of the 125 patients diagnosed with microinvasive AC died and the cause of death was rectal carcinoma., Conclusion: The authors may conclude that conservative management of patients with microinvasive AC is safe when exact evaluation of tumor extension and surgical margins of the cone are considered, and results in very low risk of recurrence, lymph node disease, and death caused by cancer.

We present a unique case of a large urinary bladder stone protruding through the external urethral meatus in a 77-year-old woman, which was causing acute urinary retention, complicated by bilateral hydronephrosis, and was removed under topical anesthesia in the emergency department. Epidemiology, etiology, clinical presentation and management of urinary bladder stones are briefly discussed., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Background: Müllerian papilloma is a rare benign tumor of the female genital tract. It mostly affects girls less than five years old. After the treatment long-term follow-up is needed as there is a chance of recurrence, but even then the prognosis is excellent., Case: A 19-year-old girl with Proteus syndrome presented with vaginal bleeding. The histological examination revealed Müllerian papilloma of the uterine cervix and large bilateral ovarian cystadenomas. The patient was treated with a radical operation, because there were signs of more aggressive behavior in the tumor. The patient is alive and free of disease five years after the operation., Conclusion: The medical care of patients affected by rare disorders depends heavily on experiences gained from cases published in the medical literature. Since there is not much experience with tumors in Proteus syndrome we believe that this case can aid in shedding light on this subject.

Objective: The objective of this analysis was to present the clinical outcome of the patients with FIGO stage IA2 squamous cell cervical cancer treated at the Department of Obstetrics and Gynecology between 1973 and 2009, and to clarify the discrepancies in clinical guidelines regarding the radicality of treatment applied in patients with stage IA2 squamous cell cervical cancer., Methods: In our study we enrolled 89 women, diagnosed with FIGO stage IA2 squamous cell microinvasive carcinoma (MIC) in the period 1973-2009. The analysis involved the following parameters women's age at operation, type of operation, cell type, mitotic activity, invasive growth pattern, host defense reaction, lymph-vascular space invasion and patient's survival. Additionally, using the Rainer's scoring system, the prognostic score for each MIC was calculated., Results: The mean women's age at operation was 41.48 ± 10.67 years. The mean depth of invasion was 3.09 ± 1.13 mm, and the mean area of carcinoma 4.05 ± 2.40 mm(2). In 66 (74.2%) women the suggested treatment was conization, according to the Rainer's scoring system and individualization of treatment based on decision of the tumor board. Three of the 89 patients diagnosed with MIC stage IA2 died; only in one patient the cause of death was cervical carcinoma. At the end of the observed period the survival rate was 98.0%., Conclusion: We may conclude that conservative management of stage IA2 MIC is safe when exact evaluation of tumor extension and surgical margins of the cone are considered, and results in very low risk of recurrence, lymph node disease, and death caused by cancer. We believe that our experience will contribute to the achievement of the international consensus concerning the treatment of IA2 MIC., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Primary embryonal rhabdomyosarcoma (RMS) arising from the uterine cervix is a rare and extremely malignant entity. Young women aged 12-26 years are mostly affected. Before the introduction of effective adjuvant chemotherapy, the prognosis of these lesions was poor., Case: A 16-year-old girl presented with vaginal bleeding. The histological examination revealed embryonal RMS of the uterine cervix. The patient was treated with a combination of surgery, chemotherapy and radiotherapy. The patient was alive and free of disease five years after the operation., Conclusion: A combined modality approach to treating RMS using surgery, multidrug chemotherapy, and radiotherapy has significantly improved survival. The medical community should keep in mind that embryonal RMS of the uterine cervix, despite its malignancy and rarity, can be cured if timely and adequate treatment is given.

Objective: The immunohistochemical (IHC) expression of topoisomerase II alpha and collagen IV was studied in cervical cancer. The results of IHC expression for both markers were compared to the clinical and histological factors predicting the course of disease., Methods: In 114 patients with cervical cancer, treated at the Department of Gynecology and Obstetrics, University Medical Centre Ljubljana between 1995 and 1999, the tumor tissue was analyzed using standard IHC staining (IHS) procedures for topoisomerase II alpha and collagen IV. The obtained results were compared to those obtained by clinical, pathomorphological and morphometric prognostic factors, and the impact of the analyzed factors on the outcome of disease was assessed., Results: A high percentage of IHC expression of topoisomerase II alpha was present in 55.3%, and to collagen IV in 28.1% of cervical cancer patients. In the multivariate analysis the IHS intensity to collagen IV was significantly associated with lymphovascular invasion (OR = 5.906; 95% CI 2.18-15.96). Kaplan-Meier analysis showed a statistically significantly better survival in initial cervical cancer stages (p = 0.001), in tumors with a higher degree of differentiation (p = 0.049), more shallow depth of invasion (p = 0.004), smaller horizontal tumor spread (p = 0.001), in cases with no lymph node metastases (p = 0.001) and no lymphovascular space invasion (p = 0.001), in younger age groups (p = 0.001) and in women with regular menstrual cycles (p = 0.001)., Conclusion: IHC expression of topoisomerase II alpha and collagen IV was significantly correlated with defense reaction. A negative and weak IHC to collagen IV was a statistically significant independent predictive variable for lymphovascular invasion, related to metastatic spread in the lymph nodes. The two analyzed IHC markers indicate the existence of factors at the molecular level that might complement the assessment of cervical cancer prognosis, resulting in the appropriate choice of type and extent of treatment.

Background: Pelvic retroperitoneal liposarcomas are rare tumors of mesenchymal origin. We present a case of a giant pelvic well-differentiated liposarcoma of the retroperitoneum in a woman, presenting with a large abdominal mass., Case: A 62-year-old woman presented with a rapid abdominal enlargement. Pelvic examination revealed a huge mass occupying the whole pelvis and part of the right abdomen. At surgery, the pelvic organs were displaced to the right side by a retroperitoneal mass that marginally involved the part of the posterior abdominal wall, left parietal peritoneum of the diaphragm, left colic flexure and the left adnexa. The huge mass, uterus, and both adnexa were removed; hemicolectomy and latero-lateral anastomosis were carried out. No adjuvant irradiation was given. The patient is alive and free of disease five years after the operation., Conclusion: The gynecologist should consider retroperitoneal liposarcoma in the differential diagnosis of large pelvic or abdominal masses.

Objective: An organized cervical cancer (CC) screening program was introduced in Slovenia in 2003. With the purpose of clinical audit we analyzed the clinicopathological characteristics of CC patients for the period between 2003 and 2005., Study Design: The retrospectively collected data of 450 CC patients were presented at three Advisory Boards of Gynecologic Oncology in Slovenia. They were stratified for stage, tumor characteristics and treatment methods according to gynecologic examination attendance in the last 5 years preceding the diagnosis of CC (attenders vs. nonattenders)., Results: In the period of observation, 242 women (53.8%) visited their gynecologists in the 5-year period prior to diagnosis of CC. Squamous cell carcinoma was present in 378 women (84.0%), adenocarcinoma in 45 (10.0%), adenosquamous carcinoma in 24 (5.3%) and other types in 3 women (0.7%). Attenders were significantly more frequently diagnosed with squamous cell carcinoma than nonattenders (chi-square=5.13; P<0.05). Attenders were significantly more frequently diagnosed in stage IA than in stage IB (chi-square=22.35; P<0.01). Similarly, in attenders stage I was significantly more frequent than stage II (chi-square=18.81; P<0.01). Pathologic smears of women with CC in the last 5-year period were most frequently evaluated as Pap II in the years 2003 and 2004 (in 39.1 and 26.4% of women, respectively) and as Pap III (in 27.9% of women) in 2005. Surgery was performed in 282 women (62.7%), radiotherapy in 158 (35.1%), symptomatic therapy in 9 (2.0%) and chemotherapy alone in 1 (0.2%) woman. In attenders, surgery alone was the most frequent treatment method (chi-square=91.18; P<0.01)., Conclusion: Only in attenders a significant redistribution of CC stages in favor of early stages is observed, and in these women more conservative and less extensive treatment methods could be applied.

Purpose of Investigation: From 2003 to 2006 the data on Slovenian cervical cancer patients who regularly attended a gynecologist were gathered. Data were analyzed in order to improve the efficiency of the cervical cancer screening program., Methods: Data on all patients newly diagnosed with cervical cancer were collected at three central clinics in Slovenia. The results are a presentation and comparison of detailed information on some characteristics of cervical cancer patients of the group that regularly visited a gynecologist and of the other group who did not. Data were processed by descriptive epidemiological methods. Mantel-Haenzel chi2 and Fisher's p tests were used to evaluate statistical significance., Results: On average, 55% of patients with cervical cancer underwent a gynecological examination five years before the diagnosis. The patients who regularly attended their gynecologist were, in all age groups, statistically significantly younger, the stage of cervical cancer at diagnosis was statistically significantly lower (p = 0.01) and were, in statistically significantly higher percentage, treated surgically (p < 0.01). From 2003 to 2006, each patient had on average five examinations at her gynecologist within the period of five years to six months before the diagnosis of cervical cancer. The average number of collected smear samples was 3.2., Conclusion: From the results of our analysis, it may be concluded that improvements are needed in Slovenia in the field of screening for and early detection of cervical cancer.

Purpose of Investigation: The data gathered in 2003 on the patients with cervical cancer who regularly attended their gynecologist were analyzed with the purpose of clinical audit., Methods: The data on newly detected patients with cervical cancer in 2003 who regularly attended their gynecologist were gathered simultaneously at three Advisory Boards for Gynecology in Slovenia., Results: Of 149 patients in whom, according to our data, invasive cervical cancer had been diagnosed, 92 (61.7%) patients were examined by a gynecologist in the previous five years. In the majority of these patients, cervical cancer was diagnosed in early, localized disease stage. In the periods of 13-24 and of seven to 12 months before the diagnosis of cervical cancer, almost half the patients had Pap II, and three to six months before diagnosis, 67.6% of patients had Pap II., Conclusion: These results encourage us to proceed with clinical audits to analyze individual cervical cancer cases, including another independent reevaluation of cervical smears in the five-year period before diagnosis. A suitable calendar of refresher training courses on colposcopy, which should be obligatory for all performing this examination method, also needs to be set up.

Objective: In Slovenia the opportunistic cervical cancer (CC) screening programme has been performed within the regular gynaecological practice since 1960. The incidence rate 28.8/10(5) decreased to 16.1/10(5) in 1982, and increased to 23/10(5) in 1996. To explain the increased CC incidence the patients' screening histories, occurrence of symptoms, and details of preventive measures were studied on the basis of medical records and questionnaire. Errors of cytological screening were analysed by reviewing previous smears., Material: The answers obtained from 324 women, treated for CC in the period 1995-2000, were analysed in relation to age, stage and histology. The mean women's age was 46.76 +/- 13.07 (S.D.) years (range 23-85 years). After therapy, 271 patients were followed-up by the end of January 2004, (mean follow-up time 80.3 +/- 20 S.D. months, range 29.7-110.3 months). Statistical analysis was performed using Chi-square test., Results: In 208 (80%) cases, CC was detected in stage 1, in 43 (17%) in stages 2A to 3B. Squamous-cell carcinoma (192, 74.1%) was followed by adenocarcinoma (61, 23.5%) and (5, 1.9%) other malignancies. The screening interval ranged from 6 months to 4 years. Statistically significant differences existed between clinical and screening variables. CC was diagnosed in higher stages in women who were ignorant of the Pap test. Re-screened smears (n = 126) showed 27.8% of false negative results., Conclusions: The reasons for high incidence of CC are poor performance of cytological screening, failures in gynecological examinations and diagnostic procedures, and the patients' negligence of attending regular screening.