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Background: In the last two decades, tyrosine kinase inhibitors (TKIs) and advances in molecular diagnostics have revolutionized management and long-term clinical outcomes in chronic myeloid leukemia (CML). Real-world data from different countries allow for the identification of country-specific issues in the clinical management and development of specific plans for improvement. Here, we aimed to analyze the trend in overall survival in Bulgarian CML patients since 2000. Methods: We retrieved publicly available Bulgarian CML data from several sources such as the Bulgarian National Cancer Registry, Bulgarian National Statistical Institute, and National Health Insurance Fund since 2000. We used the retrieved data of a total of 1513 Bulgarian CML patients to describe the trends in overall survival (OS), conditional overall survival, life expectancy, and life years lost over five time periods. We also described the trends in healthcare expenditures for TKIs and CML patients’ coverage with TKIs since 2014. Results: In both uni- and multivariate models, we found a constant increase in OS over the three 5-year periods until 2014. The period 2015–2019 was not associated with an additional increase in OS. Identical dynamics in the improvement in life expectancy (LE) and in life years lost (LYLs) was observed. Additionally, conditional 5-year survival did not improve during 2015–2019 in comparison to 2010–2014. Population-level data did not show consistent changes in the documented number of deaths due to CML since 2013. The period after 2013 is marked by a constant increase in the annual expenditures for TKIs, reaching to about 2.0 EUR/capita. The number of patients who received at least one TKI also increased during that period. Conclusions: After the initial significant improvement in the clinical outcomes for Bulgarian CML patients until 2014, subsequent periods did not bring further benefit in spite of the improved coverage with second- and third-line TKIs. Multiple factors may contribute to these suboptimal outcomes. Therefore, one can propose several additional measures at the country level, which could lead to additional improvement in the OS of Bulgarian CML patients.

There are no specific recommendations for evaluating the Ki-67 index in heterogeneous breast carcinomas. This study aimed to evaluate the applicability of currently accepted recommendations for Ki-67 evaluation in breast cancer in the context of intratumor heterogeneity. Twelve cases of heterogeneous breast carcinomas obtained from 110 patients were retrospectively studied. Ki-67 staining was performed according to protocols provided by the reagent manufacturer. Results for Ki-67 of the separate components in each tumor were obtained, described, and analyzed statistically using a paired t-test. Values of p < 0.05 were considered as statistically significant. SPSS software was used for statistical analysis. Results from the comparison of the Ki-67 index evaluation in each heterogeneous component of the studied tumors demonstrated no statistically significant difference of mean values t = 0.4802, p = 0.6405. The anticipation of an average Ki-67 score in the evaluated cases would have changed the molecular subtype from Luminal B to Luminal A (due to the Ki-67 index below 14%) in two of the cases. Heterogeneous tumors had a different Ki-67 index in their separate components. Our observations suggest that Ki-67 in heterogeneous breast carcinoma is evaluated and reported separately for the distinguishable tumor components.

The internal iliac artery (IIA) is the main arterial vessel of the pelvis. It supplies the pelvic viscera, pelvic walls, perineum, and gluteal region. In cases of severe obstetrical or gynecologic hemorrhage, IIA ligation can be a lifesaving procedure. Regrettably, IIA ligation has not gained widespread popularity, primarily due to limited surgical training and concerns regarding possible complications, including buttock claudication, impotence, and urinary bladder and rectum necroses. Nowadays, selective arterial embolization or temporary balloon occlusion are increasingly utilized alternatives, which can be applied preoperatively or intraoperatively for threatening severe genital or pelvic bleeding. However, IIA ligation retains its relevance, as the previously described procedures are not always available and have limitations. This article provides a step-by-step guide to the IIA ligation procedure and its possible complications. It also includes a detailed description of the anatomy of the IIA and pelvic arterial anastomoses. This review highlights the importance of a thorough understanding of pelvic anatomy as a prerequisite for safe IIA ligation and posits that training in this procedure should be an integral part of obstetrics and gynecology curricula.

Hydatidosis is a zoonosis caused by the larval form of a cestode of the species Echinococcus granulosus, the canine tapeworm. It can affect any organ of the human body except nails, hair, and cornea. It most often involves the liver, lungs, muscles, and bones. Involvement of organs in the small pelvis is extremely rare, mainly secondary to dissemination of hydatidosis from another organ, and the ovaries are most often involved, followed by the uterus. We present a 41-year-old Caucasian woman with complaints of mild pain, heaviness in the small pelvis, and a fibroid detected by ultrasound examination. She had reported for 2 previous operations for echinococcus cysts, and we found cystic formations in the liver and pelvis by computed tomography. It was decided that it is a recurrence of echinococcosis with a new cyst both in ovary and uterus. A hysterectomy with adnexectomy was performed, and one year later there is no evidence of recurrence of echinococcosis. In the presence of a formation in the small pelvis, one should always think about echinococcosis, especially if there is evidence of previous manifestations of the disease. Diagnosing this disease is extremely important for proper treatment. As rare as uterine involvement is, this possibility should not be overlooked.

Angiomyomatous hamartoma (AMH) of the lymph node is an extremely rare, benign vascular disease of unknown etiology. It is characterized by partial or complete replacement of the lymph node parenchyma by irregularly distributed, thick-walled blood vessels, smooth muscle bundles and adipose tissue in a fibrotic stroma. Angiomyomatous hamartoma occurs mainly in inguinal and femoral nodal regions, but there are a few reports of some other locations – submandibular, cervical, popliteal and paraaortic lymph nodes. We present a case of a 37-old female patient with AMH in the pelvic and paraaortic lymph nodes who presented with weight loss – 7 kg in 7 months. The differential diagnosis of AMH includes lymphangiomyomatosis, which, unlike AMH, involves primarily thoracic and intra-abdominal lymph nodes: nodal leiomyomatosis with less pronounced vascular proliferation and angiomyolipoma of the lymph node. The latter is composed of the same tissues as in AMH, but the smooth muscle component shows increased cellularity, polymorphism and increased mitotic activity, as well as a typical immune profile with coexpression of melanocyte markers and estrogen, which were negative in our case. The world literature references show that this is the first reported case in which the disease manifested itself with weight loss and affected paraaortic lymph nodes in a female patient.

Detailed knowledge of the human anatomy is an integral part of every surgical procedure. The majority of surgery related complications are due to a failure to possess appropriate knowledge of human anatomy. However, surgeons pay less attention of the anatomy of the anterior abdominal wall. It is composed of nine abdominal layers, which are composed of fascias, muscles, nerves, and vessels. Many superficial and deep vessels and their anastomoses supply the anterior abdominal wall. Moreover, anatomical variations of these vessels are often presented. Intraoperative and postoperative complications associated with entry and closure of the anterior abdominal wall could compromise the best surgical procedure. Therefore, sound knowledge of the vascular anatomy of the anterior abdominal wall is fundamental and a prerequisite to having a favourable quality of patient care. The purpose of the present article is to describe and delineate the vascular anatomy and variations of the anterior abdominal wall and its application in abdominal surgery. Consequently, the most types of abdominal incisions and laparoscopic accesses will be discussed. Furthermore, the possibility of vessels injury related to different types of incisions and accesses will be outlined in detail. Morphological characteristics and distribution pattern of the vascular system of the anterior abdominal wall is illustrated by using figures either from open surgery, different types of imaging modalities or embalmed cadaveric dissections. Oblique skin incisions in the upper or lower abdomen such as McBurney, Chevron and Kocher are not the topic of the present article.

Background and Objectives: Neoplasms of the vagina are rare and account for 1–2% of all tumors of the female reproductive system. Primary neoplasms of the vagina are most often carcinomas originating from squamous or glandular epithelium. Of the primary glandular tumors, clear cell, endometrioid, and serous adenocarcinomas are the most common types, while mucinous and mesonephric types are very rare. Mucinous adenocarcinoma is histologically subclassified into endocervical and intestinal types. We add to the existing literature another case of an extremely rare gynecological neoplasm—primary vaginal mucinous adenocarcinoma (PVMAC) intestinal type associated with vaginal villous adenoma with high-grade dysplasia. We discuss the clinical, radiological and morphological features of this rare entity. Materials and Methods: We report a case of a 59-year-old woman with PVMAC intestinal type associated with vaginal villous adenoma with high-grade dysplasia. The patient was evaluated with a gynecological exam, and biopsy, curettage and tumor excision were performed. The positron emission tomography-computed tomography (PET/CT) scan, at the level of the pelvis, supported the primary location of the disease. Histological and immunohistochemical methods were applied. Results: The gynecological examination of the vagina revealed an exophytic polypoid mass with a diameter of 3 cm, located on the posterior wall, in the area of introitus vaginae. The PET/CT scan revealed a hypermetabolic malignant formation involving the vagina and anal canal, without evidence of pelvic and inguinal lymphadenopathy, and also, it excluded disease at sites other than the vagina. The histological and immunohistochemical investigations, as well as the clinical and radiological data, lent support to the diagnosis “primary vaginal mucinous adenocarcinoma intestinal type”. Conclusions: PVMAC intestinal type is a rare gynecological pathology, which presents a serious challenge for oncogynecologists, radiologists and pathologists.

Gestational trophoblastic disease (GTD) covers a range of proliferative disorders from non-neoplastic hydatid moles to malignant neoplastic conditions such as choriocarcinoma. The incidence of these diseases is low and often challenging to diagnose. Placental site trophoblastic tumour (PSTT) is the rarest form of GTD, accounting for up to 3% of all cases. We present a case of a 35-year-old patient diagnosed with PSTT mimicking an intramural pregnancy. Placental site trophoblastic tumour occurred after pregnancy, which ended as a blighted ovum. -hCG was not very high, and the patient had no complaints. The diagnosis was made after resection of formation which was accepted for intramural pregnancy. To our knowledge, this is the first such case described in the literature. A hysterectomy performed later confirmed the absence of a residual tumour after conservative intervention. The lack of distant metastases, confirmed by positron emission tomography-computed tomography scan, allowed for only hysterectomy with bilateral salpingo-oophorectomy to be performed. The patient was classified as low risk according to the World Health Organization (WHO) scoring system. Placental site trophoblastic tumour is a rare malignant tumour (despite its WHO coding) from the group of GTDs. It is not presented with a classic clinical picture, and its clinical diagnosis is challenging. However, clinicians should consider it in the case of unclear events after any type of pregnancy.

Radical hysterectomy is a central surgical procedure in gynecological oncology. A nerve-sparing approach is essential to minimize complications from iatrogenic injury to the pelvic nerves, resulting in postoperative urinary, anorectal, and sexual dysfunction. The hypogastric plexus (HP), a complex network of sympathetic and parasympathetic nerves, plays a critical role in pelvic autonomic innervation. This article offers a comprehensive overview of the surgical anatomy of the HP and provides a step-by-step description of HP dissection, with a particular emphasis on preserving the bladder nerve branches of the inferior HP. A thorough understanding and mastery of the anatomical and surgical nuances of HP dissection are crucial for optimizing outcomes in nerve-sparing gynecologic-oncological procedures.

Introduction: Cervical cancer is the fourth most common malignancy in women and the fourth leading cause of death among women. The main histological types of cervical cancer are squamous cell carcinoma—75% of all cases; adenocarcinoma—10–25%; and all other rare variants including adenosquamous carcinoma and neuroendocrine carcinoma. Squamotransitional cervical cancer is an extremely rare and poorly studied subtype of squamous cell carcinoma. Case report: We present a case of a 64-year-old female patient with early-stage squamotransitional carcinoma. A metastasis was observed in the left ovary and the left fallopian tube and a benign Brenner tumor in the right ovary. Discussion: Although it is believed that this cervical cancer subtype shares the same risk factors and prognosis as squamous cell carcinoma, it is more likely to metastasize and recur. It is not unusual for spread to exist within nearby structures like the cervix and adnexa. It is impossible to tell which is the predominant focus from the immunoprofile of the lesions. Practically speaking, the best course of action in these situations is to rule out the presence of a primary tumor in the urinary tract before clarifying the condition of the cervix, uterus, and adnexal tissues. The presence of a Brenner tumor raises the possibility of a connection between the tumor’s differentiation from a cell population and potential urothelial differentiation. Conclusion: Squamotransitional cervical cancer is a rare tumor with a poorly studied clinical behavior. Despite a shortage of information in the literature, it should be regarded as a more aggressive variety of squamous cell carcinoma and, as such, should be treated and followed up more aggressively. This case is the first described with involvement of the cervix, endometrium, and adnexal structures and a concomitant Brenner tumor.

Currently, unlike in the past, the endometrial cavity is not considered to be sterile. The endometrium is supposed to be dominated by Lactobacilli, but also their deficiency can be found in the reproductive tract of asymptomatic healthy women. Sometimes the endometrial microbiome is dominated by various pathological microorganisms, and this can lead to various conditions as chronic endometritis, chorioamnionitis and preterm birth. Their presence causes uterine inflammation and infection, release of pro-inflammatory molecules, uterine contractions, disruption of cervical barrier, premature rupture of membranes. Uterine dysbiosis is associated with recurrent implantation failure and recurrent miscarriages. As the microbiome is important for maintaining immunological homeostasis at the level of gastrointestinal tract Lactobacilli may play a similar function at the level of uterus. The lactobacillus-dominated uterine microbiome is of great importance for maintaining a hostile uterine microenvironment, embryo implantation, early pregnancy development and normal pregnancy outcome.

Sarcomas of the uterine corpus are rare malignant neoplasms, which are further classified into mesenchymal tumors, and mixed (epithelial plus mesenchymal) tumors. The main issues concerning these neoplasms are the small number of clinical trials, insufficient data from evidence-based medicine, insignificant interest from the pharmaceutical industry, all of which close a vicious circle. The low frequency of these malignancies implies insufficient experience in the diagnosis, hence incomplete surgical and complex treatment. Additionally, the rarity of these sarcomas makes it very difficult to develop clinical practice guidelines. Preoperative diagnosis, neoadjuvant and adjuvant chemoradiation, target and hormone therapies still raise many controversies. Disagreements about the role and type of surgical treatment are also often observed in medical literature. There are still insufficient data about the role of pelvic lymph node dissection and fertility-sparing surgery. Pathologists’ experience is of paramount importance for an accurate diagnosis. Additionally, genetics examinations become part of diagnosis in some sarcomas of the uterine corpus. Some gene mutations observed in uterine sarcomas are associated with different outcomes. Therefore, a development of molecular classification of uterine sarcomas should be considered in the future. In this review, we focus on the epidemiology, pathogenesis, pathology, diagnosis and treatment of the following sarcomas of the uterine corpus: leiomyosarcoma, low- and high-grade endometrial stromal sarcomas, undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are excluded as they represent an epithelial tumor rather than a true sarcoma.

Introduction: Ovarian cancer is the leading cause of death among all gynecological malignancies. Most patients present with an advanced stage of the disease. The routes of spread in ovarian cancer include peritoneal dissemination, direct invasion, and lymphatic or hematogenous spread, with peritoneal and lymphatic spread being the most common among them. The flow direction of the peritoneal fluid makes the right subphrenic space a target site for peritoneal metastases, and the most frequently affected anatomical area in advanced cases is the right upper quadrant. Complete cytoreduction with no macroscopically visible disease is the most important prognostic factor. Methods: We reviewed published clinical anatomy reports associated with surgery of the liver in cases of advanced ovarian cancer. Results: The disease could disseminate anatomical areas, where complex surgery is required—Morrison’s pouch, the liver surface, or porta hepatis. The aim of the present article is to emphasize and delineate the gross anatomy of the liver and its surgical application for oncogynecologists. Moreover, the association between the gross and microscopic anatomy of the liver is discussed. Additionally, the vascular supply and variations of the liver are clearly described. Conclusions: Oncogynecologists performing liver mobilization, diaphragmatic stripping, and porta hepatis dissection must have a thorough knowledge of liver anatomy, including morphology, variations, functional status, potential diagnostic imaging mistakes, and anatomical limits of dissection.

Psammocarcinoma is a rare subtype of serous epithelian neoplasms arising from the ovaries and the peritoneum. It is characterized by massive psammoma body formation, low-grade cytological features, and invasiveness. We present a case of a 59-year-old female diagnosed with relapse of ovarian psammocarcinoma. She was operated 4 years previously and did not undergo chemotherapy. We performed a systematic search on this topic using the PubMed and ScienceDirect databases. In the literature 33 cases of ovarian psammocarcinoma are reported. We discuss the clinicopathological features of these patients. Ovarian psammocarcinoma is a rare and not well described disease. Due to the small number of cases found in the literature, no conclusions can be drawn about the tumour characteristics.

Background: Ovarian carcinoma (OC) is usually diagnosed at an advanced stage, necessitating a multimodal approach that includes surgery and systemic therapy. The incidence of OC is approximately five times higher in women over 65 years of age. Cardiovascular comorbidities and type 2 diabetes mellitus, both prevalent at this age, can influence therapeutic strategy and have an adverse effect on survival. Objectives: Our study aimed to determine the impact of cardiovascular diseases and diabetes mellitus on survival in advanced ovarian cancer. Materials and methods: From 2004 to 2012, we retrospectively studied 104 patients with advanced epithelial ovarian cancer (FIGO stage II–IV) who underwent surgical treatment at the Gynecology Clinic, St. Anna University Hospital, Varna, Bulgaria. Patients were followed for an average of 90 (52–129) months. We divided the study population into two groups: those with concurrent cardiovascular diseases and type 2 diabetes mellitus (CVD) and those without these comorbidities (No-CVD group). Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared between groups using Kaplan–Meier survival analysis. Cardiovascular comorbidities and diabetes mellitus were evaluated for their prognostic value for survival using multivariate Cox proportional regression analysis adjusted for age, stage of OC, grade and histological type of the tumor, ascites presence, residual tumor size (RT), performance status, and type of hysterectomy. Results: The Kaplan–Meier analysis showed reduced OS and DSS in the CVD group compared to the No-CVD group. The median OS was 24.5 months (95% CI 18.38 months) and 38 months (95% CI 26, not reached), respectively (Log-rank p = 0.045). The median DSS was 25.5 months (95% CI 19.39 months) and 48 months (95% CI 28, not reached), respectively (Log-rank p = 0.033). The Cox regression multivariate analysis established a lower (by 68%) overall survival rate for the CVD patient group than the No-CVD group, approaching statistical significance (HR 1.68, 95% CI 0.99, 2.86, p = 0.055). Cardiovascular diseases and diabetes were associated with a 79% reduction in DSS (HR 1.79, 95% CI 1.02, 3.13, p = 0.041) and a twofold increase in the risk of disease progression (HR 2.05, 95% CI 1.25, 3.37, p = 0.005). Conclusions: According to our study, cardiovascular comorbidities and diabetes may adversely affect OC survival. Optimal control of cardiovascular diseases, diabetes mellitus, and their risk factors may be beneficial for patients with advanced OC. Further research involving a larger patient population is necessary to establish these comorbidities as independent prognostic factors.

Pseudomyxoma peritonei (PMP) is a rare and uncommon condition, characterized by the presence of mucinous ascites in the abdominal cavity. The most common cause of PMP is mucinous adenocarcinoma of the appendix, followed by neoplasms of the ovary, endocervix, fallopian tube, alimentary organs, urachus, urinary bladder, lung, mucinous cyst of the spleen, and breast. Herein, we report a case of a 64-year-old postmenopausal woman (gravida 2, para 2) who presented at the department of gynecology with a short history of nausea and abdominal distention. Abdominal and vaginal ultrasonography showed a large amount of free fluid in the pelvis with hyperechoic echogenicity and right pelvic tumor with mixed echogenicity. Computed tomography demonstrated the presence of a heterogeneous, hypodense mass, without contrast enhancement, located on the right side of the pelvis, near the right ovary. Laparotomy was performed. Revision of the abdominal cavity revealed a large amount of yellow gelatinous mucinous ascites – approximately 1.5 l. A tumor (6 x 7 cm in diameter), arising from the appendix and located in the pouch of Douglas near the right ovary, was observed. Histopathology examination revealed poorly differentiated mucinous appendiceal adenocarcinoma, comprising up to 50% signet ring cells. Gastrointestinal tumors such as appendiceal neoplasms combined with PMP may mimic ovarian carcinomas. Computed tomography, abdominal/vaginal ultrasonography and tumor marker levels (carcino-embryonic antigen, carbohydrate antigen 19.9, carbohydrate antigen Ca-125) may establish the diagnosis. A differential diagnosis with appendiceal tumors should be considered for patients with right pelvic masses.

Background: Prenatal inguinoscrotal hernia is a rare condition and currently there are only several reports in the literature. Materials: We present a case of inguinoscrotal hernia in a 37-weeks’ gestation fetus, diagnosed at routine prenatal ultrasound. Surgical anomaly correction was done two months after Cesarian section in 39 weeks’ gestation. Results: We discussed the differential diagnosis of scrotal tumor formations that may occur prenatally. We performed a systematic literature review to provide useful information for the diagnosis and the management of this rare prenatal pathology. Discussion: Inguinoscrotal hernia occurs in both single or multifetal pregnancies with no side predilection; it does not mandate a change in the mode or time of delivery with recommendations for correction shortly after birth. Currently, there are no long-term follow-up data about fertility issues in fetuses with inguinoscrotal hernia in their adolescence.

The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial component of the Skp1-Cullin1-F-box (SCF) complex, which is a ubiquitin ligase. This complex aids in the degradation of many oncoproteins, such as cyclin E, c-JUN, c-MYC, NOTCH, and MCL1, via the ubiquitin-proteasome system (UPS). The FBXW7 gene is commonly mutated or deleted in numerous types of cancer, including gynecologic cancers (GCs). Such FBXW7 mutations are linked to a poor prognosis due to increased treatment resistance. Hence, detection of the FBXW7 mutation may possibly be an appropriate diagnostic and prognostic biomarker that plays a central role in determining suitable individualized management. Recent studies also suggest that, under specific circumstances, FBXW7 may act as an oncogene. There is mounting evidence indicating that the aberrant expression of FBXW7 is involved in the development of GCs. The aim of this review is to give an update on the role of FBXW7 as a potential biomarker and also as a therapeutic target for novel treatments, particularly in the management of GCs.

Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets. Methods: We developed and validated a two-gene prognostic score (2-PS) using three independent publicly available gene expression datasets. The 2-PS was built using the Robust Likelihood-Based Survival Modeling with Microarray Data method. Results: We narrowed down the model building to the analysis of 179 genes, which have been shown previously to be of importance to MPM development. Our statistical approach showed that a model including two genes (GOLT1B and MAD2L1) was the best predictor for overall survival (OS) (p < 0.0001). The binary score based on the median of the continuous score stratified the patients into low and high score groups and also showed statistical significance in uni- and multivariate models. The 2-PS was validated using two independent transcriptomic datasets. Furthermore, gene set enrichment analysis using training and validation datasets showed that high score patients had distinct gene expression profiles. Our 2-PS also showed a correlation with the estimated infiltration by some immune cell fractions such as CD8+ T cells and M1/2 macrophages. Finally, 2-PS correlated with sensitivity or resistance to some commonly used chemotherapeutic drugs. Conclusion: This is the first study to demonstrate good performance of only two-gene expression-based prognostic scores in MPM. Our initial approach for features selection allowed for an increased likelihood for the predictive value of the developed score, which we were also able to demonstrate.

Background and Objectives: The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in the antitumor immune response (IR). By interacting both with each other and with tumor cells, different immune mechanisms are activated or inhibited, which can suppress or promote the development and progression of cervical cancer (CC). Our aim was to investigate some of the main components of the cellular immune response in TME—tumor-infiltrating cytotoxic T cells (Tc, CD8+) and tumor-associated macrophages (TAMs, CD68+)—in patients with CC. Materials and Methods: We analyzed 72 paraffin-embedded tumor tissues of patients diagnosed and treated at Medical University Pleven, Bulgaria. Patients were classified according to the 2018 FIGO (International Federation of Gynaecology and Obstetrics) classification. From each patient, we selected one histological slide with hematoxylin eosin staining. In a microscopic evaluation, CD8+ T lymphocytes and CD68+-positive macrophages were counted in the tumor and stroma of five randomly selected fields at ×40 magnification (HPF). We analyzed the relationship between intratumoral and stromal CD8 and CD68 expression and FIGO stage and N status. Results: There was no significant association between the expression levels of intratumoral and stromal CD68+ cells in the different FIGO stages and according to the lymph nodes’ involvement. For CD8+ cells, the association of stromal infiltration was also not found, but T intratumor infiltration was associated with a higher FIGO stage, despite the fact that the results did not reach significance (p = 0.063, Fisher test). Intratumoral CD8+ cells were significantly associated with positive N status, (p = 0.035). Discussion: The separation of tumor-infiltrating cytotoxic T cells and tumor-associated macrophages into intratumoral and stromal is inconsequential. In our study, the level of infiltration of CD68+ cells in tumors and stromata was not significantly associated with tumor progression or lymph node involvement. The results were different for CD8+ cells, in which levels of infiltration were associated with lymph nodes’ statuses. Conclusions: The separate evaluation of CD68+ immune cells in the TME as intratumoral and stromal is not beneficial for defining prognoses, since the presence of these cells is not associated with the patient’s stage. In our study, the presence of CD8+ cells was significantly associated with lymph node metastases. The prognostic value of the obtained results can be enriched with an additional study of the lymphocyte phenotype, including B and other subtypes of T lymphocytes, NK cells, as well as molecules involved in the immune response, such as HLA subtypes.

Preservation of reproductive function in young patients with uncompleted or unrealized reproductive plans in some malignant tumours of the female reproductive system has been a subject of study for many years, especially with the advances in assisted reproductive technologies. The main neoplasms that affect women in childbearing age are cervical cancer and ovarian tumours. In the current survey the novelties in the literature will be presented regarding the fertility preservation surgery in cervical cancer with size of tumour between 2 and 4 cm, granulosa cell ovarian tumours, and epithelial borderline ovarian tumours

Vulvar leukoplakia is not a histological diagnosis and involves several diseases. Most commonly, these are vulvar lichen sclerosus and squamous cell hyperplasia of the vulva. These two conditions have similar aetiology, clinical presentation and treatment but different histopathological changes. They both lead to significant impairment of quality of life, risk of malignancy, as well as recurrence after treatment. Treatment of these conditions includes topical corticosteroids as a first-line therapy, but they have their side effects and not all patients are receptive to this therapy. This requires the use of alternative therapeutic options such as topical calcineurin inhibitors, topical and systemic retinoids, other steroid creams, various destructive techniques and, as a last resort, surgical removal of affected tissues. Surgical treatment should be avoided, despite the malignant potential, because of recurrence risk in both diseases New therapeutic approaches are coming into effect in gynaecological practice due to potential risks of the above-mentioned methods. Platelet-rich plasma therapy, ablative and non-ablative laser treatment, and new topical medicines, are some of the new options applied to improve the efficacy of treatment avoiding the side effects of conventional medications. A number of them are still in their initial phase of application and time will tell their effectiveness.

Chronic vulvar pain or discomfort for which no obvious aetiology can be found, i.e. vulvodynia, can affect up to 16% of women, and it may be found in girls and women across all age groups and ethnicities. Most patients describe it as burning, stinging, irritation, or rawness. The symptoms may spread to the whole vulva (generalised vulvodynia) or only to part of it, such as the clitoris (clitorodynia) or the vestibule of the vagina (vestibulodynia). This condition is often underreported and underrecognised by health care providers. Vulvodynia is a significant burden to society, the health care system, the affected women, and their intimate partners. It has a negative impact on quality of life. Vulvodynia is a diagnosis of exclusion with unknown aetiology. The gynaecologist plays a key role in excluding other causes of vulvar pain, and collaborating with other health care providers to manage the patient’s pain. Although many therapeutic options are available, such as vulvar care measures, psychological approaches, local treatment, oral medications, surgical procedures, electrical nerve stimulation, and laser therapy, there is no single treatment effective for all patients. That is why individualised management is needed. An individualised, holistic, and often multidisciplinary approach is needed to effectively manage the patient’s pain and pain-related distress.

Introduction. Exaggerated placental site reaction is a rare benign non-neoplastic lesion and presents with infiltration of the endometrium and myometrium by intermediate trophoblastic cells at the implantation site. This reaction may occur following healthy or ectopic pregnancy, aborts, or molar pregnancy. The diagnosis is only histopathological. Case report. We present a 44-year-old woman with prolonged menstrual bleeding, high levels of beta-hCG and ultrasound finding mimicking submucosal fibroid. Hysterectomy was performed because of the formation in the uterine cavity. The diagnosis made was exaggerated placental site reaction. Conclusions. Exaggerated placental site reaction is a benign condition, but this lesion has to be differentiated from placental site nodule, placental site trophoblastic tumor and choriocarcinoma because the latter require aggressive treatment.

Introduction: Cervical cancer is the fourth most prevalent malignancy and the fourth leading cause of cancer-related death in women around the world. Histologically, squamous cell carcinoma (SCC) is the most common form of cervical cancer. SCC has several subtypes, and one of the rarest is papillary squamotransitional cell carcinoma (PSCC). In general, PSCC is believed to have a similar course and prognosis to typical SCC, with a high risk of late metastasis and recurrence. Case report: We discuss the case of a 45-year-old patient diagnosed with PSCC who was admitted to our department in December 2021. The clinical manifestations were pelvic discomfort and lymphadenopathy throughout the body. On admission, all laboratory values, with the exception of C-Reactive Protein (CRP) at 22.35 mg/L and hemoglobin (HGB) at 87.0 g/L, were normal. The clinical and ultrasound examination revealed a painful formation with indistinct borders in the right portion of the small pelvis. Following dilation and curettage, a Tru-Cut biopsy of the inguinal lymph nodes was performed. The investigation histologically indicated PSCC. MRI of the small pelvis showed an endophytic tumor in the cervix with dimensions of 35/26 mm and provided data for bilateral parametrial infiltration; a hetero-intensive tumor originating from the right ovary and involving small intestinal loops measuring 90/58 mm; and generalized lymphadenopathy and peritoneal metastases in the pouch of Douglass. The FIGO classification for the tumor was IVB. The patient was subsequently referred for chemotherapy by the tumor board’s decision. Discussion: Despite the generally good prognosis of SCC, PSCC is a rare and aggressive subtype. It is usually diagnosed at an advanced stage and has a poor prognosis. Conclusions: PSCC is a rare subtype of SCC, and its diagnosis and treatment are challenging.

Introduction: Cancer of the uterine cervix (CUC) is still one of the most frequent oncological diagnoses in women. The specific interactions between the tumor cells of CUC and the cells and tissues in the tumor microenvironment can affect cancer cells’ invasive and metastatic potential and can modulate tumor’s progression and death. CD47 is a trans-membranous immunoglobulin, expressed in many cells. It protects the cells from being destroyed by the circulating macrophages. Aim: We aimed to evaluate the prognostic role of CD47 expressed in the tumor tissues of patients with CUC for tumor progression and to find the most sensitive immunohistochemical score for defining the cut-off significantly associated with tumor biology and progression. Materials and methods: Paraffin-embedded tumor tissues from 86 patients with CUC were included in the study. Clinico-morphological data for patients, such as age and stage at diagnosis according to FIGO and TNM classification, were obtained from the hospital electronic medical records. Immunohistochemical staining was performed with rabbit recombinant monoclonal CD47 antibody (Clone SP279). The final result was interpreted based on three reporting models in immunohistochemistry: H-score, Allred score and combined score. Results: The expression of CD47 was higher in tumors limited in the cervix compared with those invading other structures, and it did not depend on the nodal status. The results of immunohistochemical staining were similar regardless of which immunohistochemical method was used. The most significant correlation with TNM stage was observed with the H-score (p = 0.00018). The association with the Allred and combined score was less significant, with p values of 0.0013 and 0.0002, respectively. Conclusion: The expression of CD47 in the cancer cells is prognostic for tumor invasion in the surrounding structures, independent of lymph node engagement. The H-score is the most sensitive immunohistochemical score to describe tumor stage. To the best of our knowledge, this is the first study evaluating the significance of CD47 expression in CUC.

Background and Objectives: Cancer patients are at increased short- and long-term risk of cardiac toxicity and mortality. It is well-known that cardiac morbidity and mortality follows a seasonal pattern. Here we address the question of whether heart disease-related fatalities among cancer patients also follow a seasonal pattern. Materials and Methods: We performed a retrospective analysis of seasonality of deaths due to heart diseases (n = 503,243) in patients with newly diagnosed cancer reported during the period from 1975 to 2016 in the US’s largest cancer registry—the Surveillance, Epidemiology, and End Results (SEER) database. Seasonality was assessed through a classical cosinor model assuming a single annual peak. Results: We identified a significant seasonal peak in the first half of November. A peak with identical features was for all subgroups of patients defined based on demographic characteristics. This was also the case when analysis was performed on subgroups defined by the type of malignancy. Only patients with acute leukemias, pancreatic cancer and nervous system malignancies did not have a seasonal pattern in heart disease-related fatalities. Conclusion: the rate of heart disease-related fatalities after cancer diagnosis follows a seasonal pattern similar to that observed for the general population, albeit with an earlier peak in November. This suggests that close monitoring of the cardiovascular system in cancer survivors must be particularly active from late autumn and during the entire winter period.

Lymphoepithelioma-like breast carcinoma (LELC) is a rare type of malignant breast tumor that is not included in the current edition of the World Health Organization (WHO) classification of breast tumors. Currently, there are no clearly defined therapeutic strategies, and the general information on breast LELC is based on sporadic clinical cases described in the medical literature. We present a clinical case that describes a 49-year-old woman with a tumor formation in the right breast, histologically verified as LELC, together with a non-palpable, synchronous high-grade invasive ductal carcinoma and ductal carcinoma in situ Grade 2 (DCIS G2) in a different quadrant of the same breast. To our knowledge, this is the first case described in the literature that combines a LELC with a synchronous carcinoma in the same breast.

Vulvar cancer (VC) is a rare disease, of which the squamous vulvar carcinomas (SVCs) are the most common histological subtype. SVC is often associated with human papillomavirus (HPV) infection. HPV- positive SVCs are multifocal, typically have non-keratinizing morphology, presence of koilocytes and tend to arise in younger women (

Background: The median sacral artery (lat. arteria sacralis mediana) [MSA] is a small vessel that arises from the dorsal aspect of the aorta just above its bifurcation. It passes through the presacral space and descends in the midline, anterior to the fourth and fifth lumbar vertebrae, sacrum and coccyx, and posterior to the common iliac vein or iliocaval junction. Case report: Herein we describe two cases of MSA running in front of the left common iliac vein. To the best of our knowledge, MSA passing anterior to the left common iliac vein has previously been reported only once.The risk of damaging the artery, when located anterior to the left common iliac vein is increased in gynecological procedures in the presacral region – sacrocolpopexy or sacrohysteropexy, presacral neurectomy, retroperitoneal presacral tumors resection, selective lymphadenectomy, and sentinel lymph node biopsy. Conclusions: Damaging the MSA can result in massive hemorrhage, especially when it is retracted into the sacral foramina.The MSA is regularly found during dissections in the presacral region, not only in gynecological procedures, but also during anterior lumbar spine, urologic and orthopedic surgeries.

The surgical treatment of gynecological malignancies is, except for tumors diagnosed at the earliest stages and patients’ desire for fertility preservation, not limited to only the affected organ. In cases of metastatic iliac lymph nodes, gynecological tumors or recurrences located near the pelvic sidewall, oncogynecologists should dissect tissues in that region. Moreover, surgery of deep infiltrating endometriosis, e.g., within the sacral plexus, or oncological procedures, such as a laterally extended endoplevic resection or a laterally extended parametrectomy, often require a dissection of the pelvic sidewall. Dissection should be meticulous, and detailed knowledge of anatomy is mandatory. There are many controversies among authors regarding the terminology in the pelvic sidewall. In particular, several imprecise or confusing definitions exist in regard to the region located medially to the psoas major muscle. Therefore, after discussing the anatomy of the pelvic sidewall and the commonly used terminology, we define a new term and boundaries of a potential avascular space, the medial psoas space. Contrary to the variety of earlier definitions, the proposed boundaries relate to a truly avascular space and could help surgeons to avoid complications resulting from misleading anatomical descriptions. Additionally, describing the clear boundaries of and possible anatomical variations in the medial psoas space may urge oncogynecologists to consider different approaches during surgery. The purpose of the present study is to describe the anatomy of the pelvic sidewall and the applications of the medial psoas space in gynecologic oncology.

Endometrioid endometrial adenocarcinoma (EEC) is the most common malignancy of the female genital tract. According to the 2009 FIGO staging system, the depth of myometrial invasion (MI), and tumor spread to adjacent organs or tissues are the staging criteria for endometrial carcinoma (EC). Therefore, assessment of the depth of MI is of great importance. There is a spectrum of morphological patterns of MI. Still, their number and features vary according to the scientific literature, with a certain overlap that creates difficulties and controversies in the precise assessment of MI depth. The purpose of this review is to present and discuss the most important and recent information about patterns of MI, focusing on the more aggressive and the elongated and fragmented glands (MELF) pattern in particular. Assessment of MI depth and correct staging of EC is possible only after the precise recognition of each MI pattern.

Pelvic lymphadenectomy is a common surgical procedure in gynecologic oncology. Pelvic lymph node dissection is performed for all types of gynecological malignancies to evaluate the extent of a disease and facilitate further treatment planning. Most studies examine the lymphatic spread, the prognostic, and therapeutic significance of the lymph nodes. However, there are very few studies describing the possible surgical approaches and the anatomical variations. Moreover, a correlation between anatomical variations and lymphadenectomy in the pelvic region has never been discussed in medical literature. The present article aims to expand the limited knowledge of the anatomical variations in the pelvis. Anatomical variations of the ureters, pelvic vessels, and nerves and their significance to pelvic lymphadenectomy are summarized, explained, and illustrated. Surgeons should be familiar with pelvic anatomy and its variations to safely perform a pelvic lymphadenectomy. Learning the proper lymphadenectomy technique relating to anatomical landmarks and variations may decrease morbidity and mortality. Furthermore, accurate description and analysis of the majority of pelvic anatomical variations may impact not only gynecological surgery, but also spinal surgery, urology, and orthopedics.

Introduction. Ovarian carcinosarcoma (OCS), also known as malignant mixed Müllerian tumour (MMMT), is one of the rarest histological subtypes of ovarian cancer. It is an aggressive tumour with a dismal prognosis—the median survival of patients is less than two years. The rarity of the disease generates many controversies about histogenesis, prognostic factors and treatment of OCS. Histologically, OCS is composed of an epithelial and sarcomatous component. Case report. In the present case, a patient with bilateral ovarian cysts and bulky paraaortic lymph nodes is reported. Retroperitoneal paraaortic lymph node metastases were the only extrapelvic dissemination of OCS. The patient underwent comprehensive surgical staging procedures, including total abdominal hysterectomy and bilateral salpingo-oophorectomy, supracolic omentectomy and selective para-aortic lymphadenectomy. Histologically the ovarian carcinosarcoma was composed of an epithelial component (high-grade serous adenocarcinoma) and three sarcomatous components (homologous—endometrial stromal cell sarcoma, and heterologous—chondrosarcoma, rhabdomyosarcoma). Immunohistochemistry staining was performed. A postoperative complication (adhesion between the abdominal aorta and terminal ileum causing obstructive ileus) that has never been reported in the medical literature occurred. Conclusion. Carcinosarcomas are carcinomas with epithelial–mesenchymal transition and heterologous differentiation. Retroperitoneal pelvic and paraaortic lymph nodes should be carefully inspected in patients with ovarian tumours. Adhesions between the small bowels and abdominal aorta are possible complications after lymph node dissection in the paraaortic region.

Uterus didelphys is a rare form of congenital anomaly of the Müllerian ducts. The clinical significance of this anomaly of the female reproductive tract is associated with various reproductive issues: increased risk of preterm birth before 37 weeks’ gestation, abnormal fetal presentation, delivery by caesarean section, intrauterine fetal growth restriction, low birth weight less than 2500 g, and perinatal mortality. We present three cases of uterus didelphys and full-term pregnancy, which resulted in favorable birth outcomes of live-born, full-term infants. In two of the cases, delivery was performed via Caesarean section: due to lack of labor activity in one of the cases and lack of response to oxytocin stimulation in the second case. The weight of two of the new-born infants was lower than expected for the gestational age.

Introduction: Potter’s syndrome, also known as Potter’s sequence, is an uncommon and fatal disorder. Potter’s sequence in a multiple pregnancy is uncommon, and its frequency remains unknown. Worldwide in a diamniotic twin pregnancy, there are only a few cases described. Case report: We present an unusual case discordance for Potter’s syndrome in a dichorionic diamniotic twin pregnancy. Twin A had the typical physical and histological Potter’s findings. Twin B had normal respiratory function and normal physical examination findings. There are many controversies about this condition in diamniotic twin pregnancy. One case report concluded that that the presence of a normal co-twin in diamniotic pregnancy prevented the cutaneous features seen in Potter’s syndrome and ameliorated the pulmonary complications, whereas two other case studies reported that the affected twin had extrarenal features typical of the syndrome. Conclusion: We performed an autopsy and calculated lung weight/body weight ratio to diagnose pulmonary hypoplasia. Histopathologic examination of lungs and kidneys was performed. We concluded that the appearance of extrarenal features in the affected twin depends on the amniocity.

Background and objectives: Adenosquamous cancer of the uterine cervix is a rare type of cervical cancer with both malignant squamous and glandular components. A very rare subtype is mucoepidermoid carcinoma (MEC), which was first described as a salivary gland tumor. It has been described as having the appearance of a squamous cell carcinoma without glandular formation and contains intracellular mucin. The postoperative evolution of this tumor and the potentially poorer prognosis may indicate an intensification of the follow-up. The objective of our study was to analyze the frequency of mucoepidermoid carcinoma in hospitalized women with cervical cancer, clinical characteristics and prognosis. Material and Methods: A retrospective study of all cases of mucoepidermoid carcinoma of the cervix at Department of Gynecologic Oncology, University Hospital—Pleven, Pleven Bulgaria between 1 January 2007 and 31 December 2016 was performed. All patients were followed-up till December 2019. We analyzed certain clinical characteristics of the patients; calculated the frequency of mucoepidermoid carcinoma of the cervix from all patients with stage I cervical cancer; and looked at the overall survival rate, correlation between overall survival, lymph node status and the size of the tumor. Results: The frequency of MEC was 1.12% of all patients with stage I cervical cancer in this study. The median age of the patients with MEC was 46.7 years (range 38−62). Four patients (57.1%) were staged as FIGO IB1, and three patients (42.8%) were FIGO IB2. The size of the primary tumor was 4 cm in 3 patients (42.8%). Metastatic lymph nodes were found in two patients (28.57%), and nonmetastatic lymph nodes were found in five patients (71.43%). There were two (28.57%) disease-related deaths during the study period. The five-year observed survival in the MEC group was 85.7% and in the other subtypes of adenosquamous cancer group was 78.3%. Conclusions: MEC of the uterine cervix is a rare entity diagnosis. As a mucin-producing tumor, it is frequently regarded as a subtype with worse clinical behavior and patients’ outcomes. Nevertheless, our data did not confirm this prognosis. New molecular markers and better stratification are needed for better selection of patients with CC, which may benefit more from additional treatment and new target therapies.

Introduction: Chylous ascites is a rare form of ascites characterized by milk-like peritoneal fluid, rich in triglycerides. Clinical signs and symptoms include abdominal distention, pain, nausea, and vomiting. In gynecology, the most common cause for its occurrence is lymph dissection leading to impairment of major lymphatic vessels. There are only a few reported cases of chylous ascites arising after operations for benign diseases. Case report: We report a case of a 46-year-old female patient, who underwent laparoscopy for a myomatous node with chylous ascites occurring on post-surgery Day 2. The ascites was conservatively managed. The exact cause of the chyloperitonitis could not be determined. Conclusion: Although extremely rarely, chylous ascites may also occur in operative interventions for benign diseases in gynecological surgery.