Relationship between the gut microbiome and endometriosis and its role in pathogenesis, diagnosis, and treatment: a systematic review.

Endometriosis is a chronic inflammatory disease affecting approximately 10% of women. It is defined as endometrial tissue outside of the uterus and produces a variety of symptoms including pelvic pain, dysmenorrhea, dyspareunia, and intermenstrual bleeding. Although several theories have been postulated regarding the pathogenesis of endometriosis, no theory has provided a complete explanation, therefore limiting our progress in diagnostic tools and management of endometriosis. Recently, much attention has been paid to the importance and role of the gut microbiome in endometriosis. As defined by Joshua Lederberg - microbiome is a set of the genome of microorganisms inhabiting a human body, including commensal, symbiotic and pathogenic microorganisms. The aim of this systematic review was to conduct a search in the Embase, Medline, and PubMed databases for literature from July 2013 to July 2023 regarding the relationship between the gut microbiome and endometriosis. 147 records were screened, of which 26 met the eligibility criteria, and 16 were included in this review. Our review concludes that patients with endometriosis show an altered gut microbiome, and that this has the potential to provide insight for pathogenesis, markers for diagnosis, as well as therapeutic options for treatment of endometriosis. Future research is necessary to confirm this and further investigate the relationship between the gut microbiome and endometriosis.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in Poland: analysis of patient series and practical guidelines for breast surgeons.

Introduction: Although breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is infrequent, with less than 1000 noted cases worldwide, patients consenting for breast implant surgery should be aware of its risk. We describe the first Polish multicenter case-series data on BIA-ALCL patients and present diagnostic and treatment recommendation for breast surgeons. Material and methods: In cooperation with the Polish Society of Surgical Oncology and Polish Lymphoma Research Group, we collected BIA-ALCL cases in Poland. Results: We retrospectively reviewed clinical data of seven BIA-ALCL patients, diagnosed between July 2013 and November 2019. The median time from implant placement to the first BIA-ALCL symptoms was 65 months (range: 33-96 months). All the patients were exposed to textured implants at presentation. Capsulectomy with implant removal was performed in all the patients with immediate reimplantation in 2 cases. In a median follow-up of 19 months (range 5-81 months), there was no recurrence and all the patients stayed alive. Between 2013 and 2019, the incidence of BIA-ALCL in Polish female population age 30 and above ranged from 0 to 0.021/100 000/year. Conclusions: BIA-ALCL is scarce in the Polish population. In a short-term follow-up, patients' prognosis remains excellent. Due to the withdrawal of roughly textured implants from the market and the exclusion of likely the most potent etiologic factor, it might be expected that the incidence of BIA-ALCL will become even rarer.

Oviductal Oxygen Homeostasis in Patients with Uterine Myoma: Correlation between Hypoxia and Telocytes.

Oxygen balance is crucial for angiogenesis, immunity, and tissue repair. The human oviduct is essential for reproductive function, and any imbalance in homeostasis leads to fertility disturbances and might be a reason for ectopic pregnancy development. Uterine myoma is a widespread benign tumour, which is often accompanied by infertility. Telocytes have been discussed in the contexts of motility, fibrosis development, and angiogenesis. We observed the oviducts from patients with and without uterine myoma, comparing the expression of HIF-1, HO, VEGF and its receptor, NOS, oestrogen, and progesterone receptors by immunolabeling. The myometrial and oviductal telocytes were also compared in both groups. Biochemical analyses were conducted for FSH, LH, AMH, sFlt, oestrogen, and progesterone in blood samples. Patients with uterine myoma have different expressions of sex steroid receptors and an increased number of telocytes. The decreasing VEFG expression was compensated by the rise in the HIF-1 and NOS expression. Blood biochemical analyses revealed a higher progesterone level and lower AMH in patients with uterine myoma. No differences in sFlt, FSH, and LF were observed. Uterine myoma impacts oviduct oxygen homeostasis and might cause fertility disturbances (uterine and oviductal infertility factors).

Breast cancer chemotherapy induces vascular dysfunction and hypertension through a NOX4-dependent mechanism.

Cardiovascular disease is the major cause of morbidity and mortality in breast cancer survivors. Chemotherapy contributes to this risk. We aimed to define the mechanisms of long-term vascular dysfunction caused by neoadjuvant chemotherapy (NACT) and identify novel therapeutic targets. We studied arteries from postmenopausal women who had undergone breast cancer treatment using docetaxel, doxorubicin, and cyclophosphamide (NACT) and from women with no history of such treatment matched for key clinical parameters. We explored mechanisms in WT and Nox4-/- mice and in human microvascular endothelial cells. Endothelium-dependent, NO-mediated vasodilatation was severely impaired in patients after NACT, while endothelium-independent responses remained normal. This was mimicked by a 24-hour exposure of arteries to NACT agents ex vivo. When applied individually, only docetaxel impaired endothelial function in human vessels. Mechanistic studies showed that NACT increased inhibitory eNOS phosphorylation of threonine 495 in a Rho-associated protein kinase-dependent (ROCK-dependent) manner and augmented vascular superoxide and hydrogen peroxide production and NADPH oxidase activity. Docetaxel increased expression of the NADPH oxidase NOX4 in endothelial and smooth muscle cells and NOX2 in the endothelium. A NOX4 increase in human arteries may be mediated epigenetically by diminished DNA methylation of the NOX4 promoter. Docetaxel induced endothelial dysfunction and hypertension in mice, and these were prevented in Nox4-/- mice and by pharmacological inhibition of Nox4 or Rock. Commonly used chemotherapeutic agents and, in particular, docetaxel alter vascular function by promoting the inhibitory phosphorylation of eNOS and enhancing ROS production by NADPH oxidases.

The effectiveness of contrast-enhanced spectral mammography and magnetic resonance imaging in dense breasts.

PURPOSE: Breast cancer is the most common cause of death from neoplastic disease in women. Among all breast anatomy types, glandular type is the most problematic concerning evaluation. While digital mammography still remains the basic diagnostic tool, one must be aware of its limitations in dense breasts. Although magnetic resonance imaging (MRI) has greatly improved sensitivity, its specificity is low. Moreover, there are contraindications for MRI for some patients, so a substitute has been searched for. This study was performed to check if contrast-enhanced spectral mammography (CESM) can be a viable option for patients with dense breasts. MATERIAL AND METHODS: The study involved 121 patients with abnormalities detected on base-line diagnostic imaging (ultrasound or mammography). The patients had subsequent examinations, both CESM and MRI performed within a maximum 2-month time interval. The sensitivity and specificity of both methods in the whole group as well as in specific breast structure types were measured and compared. RESULTS: Contrast enhancement was visible in all 121 cases on MRI, while on CESM lack of enhancement was noted in 13 cases. All of those 13 lesions turned out to be benign. There were 40 (33%) benign and 81 (69%) malignant tumours. The analysed group included 53 (44%) glandular type breast patients, 39 (32%) mixed type, and 29 (23%) fatty type. Although MRI proved to be slightly more effective in dense breasts, both methods showed similar results in the whole study group. CONCLUSION: CESM can be used with confidence in patients with glandular breast type when MRI is not available or there are reported contraindications to MRI.

Dendritic Cells Are Associated with Prognosis and Survival in Breast Cancer.

Dendritic cells (DCs) constitute a part of the tumour microenvironment, but we are still far from understanding their complex role in immune response to the tumour. This study aimed to investigate the density of DCs expressing CD1a, CD83, CD123, DC-LAMP3 (CD208) and DC-SIGN (CD209) in breast cancer. The correlations between DC density and molecular subtype of breast cancer, its hormone receptor status, spatial location and their associations with clinical and pathological prognostic factors were evaluated. We have shown that intratumoural CD1a+ cells were significantly associated with progression-free survival. For LAMP3+ and CD123+ DCs, higher cell densities were associated with non-luminal as compared to luminal cancer phenotype. In contrast, dense CD83+ DC infiltrate was observed in luminal tumours. The number of CD1a+ DCs in both locations was the highest in luminal B/HER2+ cancers. The highest positive cell count of LAMP3+ cells was observed in the triple-negative subtype in both locations. We found higher numbers of LAMP3+ DCs both intratumourally and at the invasive margin, as well as CD123+ DCs intratumourally in tumours with negative expression of oestrogen or progesterone receptors. Our study demonstrates associations between DC subpopulations and histological and clinical characteristics, as well as molecular subtypes in breast carcinoma.

Diabetic Mastopathy. Review of Diagnostic Methods and Therapeutic Options.

Diabetic mastopathy is a rare breast condition that may occur in insulin-treated men and women of any age. The etiology is still unclear; however, the autoimmunological background of the disease is highly suspected. The changes in diabetic mastopathy may mimic breast cancer; therefore, its diagnostic process is demanding, and treatment options are not clear and limited. Lesions in DM are usually multiple; therefore, surgical removal is not fully effective. A well-done anamnesis with core-needle biopsy is essential and definitive in most cases. In this review, we summarize up-to-date knowledge of diagnostic methods and therapeutic options for diabetic mastopathy treatment and present three cases of diabetic mastopathy-type lesions in ultrasound and radiological examinations.

Polish Society of Gynecology and Obstetrics statement on safety measures and performance of ultrasound examinations in obstetrics and gynecology during the SARS-CoV-2 pandemic.

We present recommendations on performance and safety measures of ultrasound examinations in obstetrics and gynecology during the SARS COV-2 pandemic. The statement was prepared based on the current knowledge on the coronavirus by the Ultrasound Section of the Polish Society of Obstetrics and Gynecology. It has to be noted that the presented guidance is based on limited evidence and is primarily based on experiences published by authors from areas most affected by the virus thus far, such as China, Singapore, Hong Kong, and Italy. We realize that the pandemic situation is very dynamic. New data is published every day. Despite the imposed limitations related to the necessity of social distancing, it is crucial to remember that providing optimal care in safe conditions should remain the primary goal of healthcare providers. We plan to update the current guidelines as the situation develops.

A Prospective Pilot Study on Use of Liquid Crystal Thermography to Detect Early Breast Cancer.

Background: Breast cancer is the most common cancer in women. While mammography is the standard for early detection in women older than 50 years of age, there is no standard for younger women. The aim of this prospective pilot study was to assess liquid crystal contact thermography, using the Braster device, as a means for the early detection of breast cancer. The device is intended to be used as a complementary tool to standard of care (sonography, mammography, etc). Patients and Methods: A total of 274 consecutive women presenting at Polish breast centers for prophylactic breast examination were enrolled to receive thermography; 19 were excluded for errors in thermographic image acquisition. The women were divided according to age (n = 135, <50 years; n = 120, ≥50 years). A control population was included (n = 40, <50 years; n = 23, ≥50 years). The primary endpoint, stratified by age group, was the C-statistic for discrimination between breast cancer and noncancer. Results: In women with abnormal breast ultrasound (n = 95, <50 years; n = 87, ≥50 years), the C-statistic was 0.85 and 0.75, respectively (P = .20), for discrimination between breast cancer and noncancer. Sensitivity did not differ (P = .79) between the younger (82%) and older women (78%), while specificity was lower in the older women (60% vs 87%, P = .025). The false-positive rate was similar in women with normal and abnormal breast ultrasound. Positive thermographic result in women with Breast Imaging Reporting and Data System (BIRADS) 4A on ultrasound increased the probability of breast cancer by over 2-fold. Conversely, a negative thermographic result decreased the probability of cancer more than 3-fold. Breast size and structure did not affect the thermography performance. No adverse events were observed. Conclusions: Thermography performed well in women <50 years of age, while its specificity in women ≥50 years was inadequate. These promising findings suggest that the Braster device deserves further investigation as a supporting tool for the early detection of breast cancer in women younger than 50 years of age.

Intraductal papilloma of the breast - management.

In light of the growing availability of ultrasound testing and invasive diagnostic methods of the breast in everyday gyneco- logic practice, lesions of uncertain malignant potential, classified histologically as B3, have become a significant health issue. Intraductal papillomas (IPs) are the most common pathology in that group of lesions. Despite their benign histologic appearance, IPs may accompany malignant growths and the diagnosis made on the basis of biopsy material carries the risk of breast cancer (BC) underestimation. The article presents a review of the available literature on the management of patients diagnosed with intraductal papilloma at a standard core needle biopsy or vacuum-assisted core needle biopsy. The management is not uniform and depends not only on the verification technique or the accompanying pathological growths, but also on the result of clinical-pathological correlations. As it turns out, open surgical biopsy should not necessarily be recommended to every affected woman, and a growing number of sources have recently suggested that a control program would be sufficient in many cases. Thus, it is vital for gynecologists to be able to differentiate between those women who may be included in the annual ultrasound control program and those who require further surgical management.

Current facts constituting an understanding of the nature of adenomyosis.

Adenomyosis seems to be the most widespread coexistent pathology included under the umbrella of common benign disorders of the human uterus. The incidence of adenomyosis is under discussion since different imaging criteria are used. In the majority of cases, prevalence is determined among women with uterine fibroids and endometriosis or severe gynecological symptoms. This common benign pathology is asymptomatic in 1/3 of cases. Up to 50% of women with infertility are affected by adenomyosis. It seems to be an important risk factor for spontaneous pre-term delivery and pre-term premature rupture of the membranes. Nowadays, the etiology of adenomyosis is still unclear and requires deeper investigation. This review summarizes the aspects of prevalence, co-existence, risk factors, classification, mechanisms of pathogenesis, genes and immunological features, main histological features, animal models, and clinical manifestation of adenomyosis. It might facilitate understanding of the independent nature of such a dual enigma as adenomyosis.

Diagnostic and prognostic relevance of microparticles in peripheral and uterine blood of patients with endometrial cancer.

OBJECTIVES: Exosomes - microvesicles which are secreted by living cells - can be produced from different cell types and detected in various body fluids. They are the carriers of intercellular information which regulate tumor microenvironment and are considered to be involved in tumor progression and metastasis. Cancer cells can secrete more exosomes than healthy cells, and are expected to be potential tools for tumor diagnosis and treatment. MATERIAL AND METHODS: In this report, we present the results of microparticle analysis in peripheral and uterine blood of patients with endometrial cancer. To the best of our knowledge, this study has been the first to report microvesicle status in peripheral and uterine blood samples. The aim of the study was to determine the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) microparticles. The counting of the selected microparticles in citrate plasma was performed using flow cytometry on the BD Canto II cytometer. RESULTS: We found that the total amount of microparticles in cancer patients was much higher than in healthy controls. Moreover, microparticle count in uterine blood was higher than in peripheral blood of patients with endometrial cancer. We also demonstrated that the amount of microparticles correlates with the histologic grade and clinical stage of the tumor. CONCLUSIONS: The most interesting finding in this work was the high level of TF, CD144 and CD14 MPs in uterine blood samples. Thus we can consider the monocyte-macrophage-derived MPs as a candidate marker of endometrial cancer and maybe very critical part of the endometrial carcinogenesis.

Telocytes: facts, speculations and myths (Review article).

Telocyte (TC) is an interstitial cell type with a small cellular body and extremely long tentacle-like extensions. TCs were discovered a decade ago and have specifc morphological characteristics, immunohistochemical and secretome profiles, electrophysiological properties, microRNA expression. Moreover, they are different in gene expression from other cells. TCs play an important role in plenty of processes. Apparently, they are involved in homeostasis, remodelling, regeneration, repair, embryogenesis, angiogenesis and even tumorigenesis. "Telocytes need the world", was emphasized by Professor Popescu and it will be actual at any time. This review summarizes particular features of TCs in different organs and systems, emphasizing their involvement in physiological and pathophysiological processes.

Endometrial cancer and hyperplasia rate in women before menopause with abnormal uterine bleeding undergoing endometrial sampling.

Introduction: Abnormal uterine bleeding (AUB) is the most common symptom of endometrial cancer (EC) and endometrial hyperplasia with (AH) or without (EH) atypia. Risk of malignancy and hyperplasia is significantly lower in premenopausal than in postmenopausal women. Only 10% of EC occurs before menopause. Obesity and age are well-recognized risk factors of endometrial cancer. Endometrial sampling is recommended in women at high risk of endometrial malignancy. The primary objective was to determine the incidence of EC, AH and EH in premenopausal women undergoing dilation and curettage (D&C) because of AUB. Additional objective of the study was to estimate the risk of EC and AH in overweight and obese women with two types of AUB: heavy menstrual bleeding (AUB-HMB) and intermenstrual bleeding (AUB-IMB), according to PALM-COEIN classification. Material and Methods: Retrospective study in the population of women undergoing D&C in tertiary hospital because of AUB between Jan-2016 and Dec-2016. The incidence of EC, AH, EH was established. The influence of the variables: age, BMI, AUBHMB/ AUB-IMB on the occurrence of abnormal histology (EC, AH, EH) was evaluated. Finally, the model built by using backward stepwise regression and mechanism of v-fold cross-validation, showed no statistically significant relationship. Results: EC was detected in 2/213 cases (0.9%; 95% CI 0.0003 to 0.036), AH in 3/213 cases (1.4%), giving a total of 5/213 (2.3%) women with AH or EC. EH was detected in 16/213 (7.5%) women. High BMI raises the chance of AH diagnosis: OR 1.16 (95% CI 1.05- 1.28). The presence of HMB compared to IMB reduces the chance of EH: OR 0.24 (95% CI 0.07-0.9). IMB increases the chance for the diagnosis of EH 4.11 times compared to HMB (OR 4.1, 95% CI 1.1-14.9; p = 0.016). Conclusions: EC in premenopausal women with AUB undergoing D&C is rare. There is a need to search for more effective methods of selection of patients than commonly used. Age and BMI do not seem to be factors that should be used to select patients.

[Fertility-sparing surgical management of ovarian cancer]. / Leczenie chirurgiczne raka jajnika z zachowaniem plodnosci.

INTRODUCTION: Ovarian cancer (OC) continues to be one of the greatest challenges of modern oncology gynecology Most patients are diagnosed in the advanced stage of the disease, which requires aggressive and extensive surgical intervention. In approximately 8% of the cases, OC affects women <40 years of age. Among them, early-stage OC FIGO IA accounts for 40% of the affected individuals, which allows for fertility-sparing surgical management. OBJECTIVES: The aim of the study was to evaluate the efficacy of fertility-sparing management in OC women, with tumor limited to one ovary who wish to preserve their fertility MATERIAL AND METHODS: A total of 43 women with OC limited to one ovary (26 with borderline malignant tumors and 17 with invasive tumor FIGO IA) underwent surgical sparing therapy Disease recurrence rate as the measure of the quality of treatment and the number of pregnancies, together with their course, as the measure of the effectiveness of the fertility-sparing therapy were evaluated. RESULTS: The observation period, from 4-10 years for borderline malignancy and 3-8 years for invasive FIGO IA tumor revealed no cases of disease recurrence. In the former group, 14 (73 %) women conceived, out of whom 2 miscarried before 22 weeks of gestation, 1 give birth pre-term, i.e. at 34 weeks of gestation, 10 (71.5%) gave birth at term, and 1 is pregnant (6 months) at the time of the publication of the study In the later group, 9 (81.8%) women conceived, out of whom 1 miscarried at 10 weeks of gestation, 1 had a case of intrauterine fetal demise at 27 weeks of gestation, 6 gave birth at term, and 1 is pregnant (3 months) at the time of the publication of the study CONCLUSIONS: Proper patients selection for fertility-sparing management, as well as the way of performing the surgery allow for adequate control of the malignant process in patients with tumor limited to one ovary and preservation of fertility

[Cesarean scar pregnancy]. / Ciaza w bliznie po cieciu cesarskim.

Pregnancy in the uterine scare after previous caesarean section is the rarest type of ectopic pregnancy Due to the possibility of life-threatening complications, cesarean scar pregnancy (CSP) needs rapid and proper diagnosis and management. Hereby we present 3 cases of women with CSP, diagnosed and treated at the Department of Gynecology and Obstetrics of Jagiellonian University Medical College, in Krakow, in 2013, as well as literature review.

[Pregnancy and labor after fertility-sparing surgical management of cervical cancer]. / Ciqza i poród u kobiet po oszczedzajacym chirurgicznym leczeniu raka szyjki macicy.

OBJECTIVE: The aim of the study was to evaluate the possibility of conception and the course of pregnancy in women with cervical cancer (FIGO IA and IB1), who underwent fertility-sparing surgical management, i.e. surgical conization or radical vaginal trachelectomy with laparoscopic lymphadenectomy. MATERIAL AND METHODS: A total of 80 patients treated surgically due to cervical cancer constituted the study group. Out of them, 65 (85%) women underwent surgical conization (43--FIGO IA1 and 25--FIGO IA2), and 12 (15%) women underwent radical vaginal trachelectomy with laparoscopic lymphadenectomy (9--FIGO IA2 and 3--FIGO lB1). Cervical cerciage was performed in all patients after trachelectomy. RESULTS: A total of 52 (76.5%) women after surgical conization successfully conceived. Out of them, 3 (5.8)% women miscarried (1 before 12 and 2 between 12-22 weeks of gestation), 2 (3.8%) delivered pre-term (at 26 and 34 weeks of gestation), and 47 (90.4%) delivered at term, including 5 (10.2%) cesarean deliveries, 1 (2.0%) vaginal delivery with the use of the Bracht Manoeuve; and 43 (87.8%) normal vaginal deliveries. Six (50.0%) women after radical vaginal trachelectomy successfully conceived. Out of them, 1 (16.7%) woman miscarried (at 19 weeks of gestation), 2 (33.3%) delivered pre-term (between 22-32 weeks of gestation), and 3 (50%) delivered at term, including 1 (20%) vaginal delivery at 25 weeks of gestation and 4 (80%) cesarean deliveries (1 at 29 weeks of gestation and 3 at term). CONCLUSIONS: Fertility-sparing surgical management in subjects with early-stage cervical carcinoma, provided the patients have been properly qualified for the procedure, allows a significant number of the affected women to conceive, have a normal pregnancy and delivery