Case report: Spontaneous rupture of leiomyosarcoma uteri 8 months after primary laparoscopic surgery of STUMP

IntroductionLeiomyosarcoma (LMS), together with smooth muscle tumors of uncertain malignant potential (STUMP) and benign leiomyomas, belongs to a heterogeneous group of uterine neoplasms. According to the World Health Organization, tumors originating from uterine smooth muscle fibers are the second most frequent tumors. It is challenging to distinguish between STUMP and LMS because of an overlap of symptoms, lack of a precise definition, and unequivocal information obtained using imaging diagnostic methods. Following myomectomy or hysterectomy with laparoscopic or laparotomy surgery and a definitive histological diagnosis of STUMP, the course of treatment is determined by the need to preserve fertility. In 2014, the U.S. Food and Drug Administration published an alert that unprotected laparoscopic morcellation is correlated with a 3-fold higher likelihood of dissemination of malignant cells and disease progression. Unprotected morcellation was independently associated with a higher risk of disease recurrence after demolition or conservative surgery, with a relative risk of 2.94.ConclusionHematoperitoneum resulting from the spontaneous rupture of a uterine tumor is a rare gynecological emergency, with very few cases reported in the last decade

Juvenile Type Granulosa Cell Tumor

Granulosa cell tumor is a type of neoplasm, which represents 2-5% of all ovarian cancers. About 5% of these tumors are juvenile- type and usually occur to girls before puberty and to women younger than thirty years of age. There are signs premature puberty or premature emergence of secondary sexual characteristics with irregular vaginal bleeding that occur to these kind of patients. To the rare cases, like this, the occurrence of granulosa cell tumors can cause the appearance of hyperandrogenism with high levels of plasma testosterone, leading to virilization which happened to this female patient. We will present the female patient who was 35 years old and which was originally hospitalized to the Clinic for Haematology Clinical Center Kragujevac, because of extreme fatigue accompanied by dizziness. During diagnostics the patient underwent to the complete gynecological examination. After gynecological examinations and necessary diagnostic procedures, it was decided continuing the treatment at the Clinic of Gynecology and Obstetrics Clinical Center Kragujevac, where she underwent a total abdominal hysterectomy with bilateral salpingo- oophorectomy for suspected uterine neoplasm. Histopathological analysis of the obtained material confirmed the presence of follicular cysts of both ovaries and juvenile type granulosa cell tumor on the right ovary; the uterus was enlarged with multiple fibroid tumors. Granulosa cell tumor should be suspected in the cases of girls and young females if there is present an ovarian cyst paired with signs of preterm puberty or hyperestrogenism. In this case, the presence of granulosa cell tumor was masked by signs of hyperandrogenism, which is not so typical, as well as the presence of uterine fibroids who have actually been the main cause for surgical treatment

Adenosarcoma Mulleri Associated with Tamoxifen use after Breast Cancer Therapy: A Case Report

The term ‘mixed Mullerian tumour’ applies to uterine tumours composed of epithelial and mesenchymal elements of Mullerian origin. These neoplasms are classified into adenomyomas, adenofi bromas, adenosarcomas, and carcinosarcomas (malignant Mullerian mixed tumours) based on whether the epithelial and stromal elements are benign or malignant. Adenosarcomas are low-grade neoplasms classified halfway along the spectrum of mixed Mullerian tumours, with adenofi bromas at one end and carcinosarcomas (malignant Mullerian mixed tumours) at the other. Adenosarcoma is a mixed Mullerian tumour composed of benignappearing but neoplastic glandular elements and a sarcomatous stroma, which is usually low grade. Histologically, there are heterologous mesenchymal elements (usually rhabdomyosarcoma, but also cartilage, fat, and other elements) in 20-25% of cases

Decline in Female Fertility After 40 Years

Important factor related to the conception possibility is women age. The decline in fertility with aging is proven and evident in literature. Infertility is increasing and many couples seek help in advanced techniques such as IVF (in vitro fertilization) in order to overcome the problem caused by aging, but the quality of the oocytes is a significant limiting factor. With the aging the quantity and quality of oocytes decreases, such as the quality of the embryo after fertilization. The accelerated rhythm of life, liberty and women inclusion in all kinds of professions brought many benefits to women, but also increasingly postponing births. Each person is unique individual, and can be more or less fertile compared to the average at same age. Unfortunately, some women has a rapid decline in fertility - accelerate aging, very early, already in the early twenties and when testing them with different methods and exams, the result is very low number of oocytes, low value of anti-Müllerian hormone and also very poor quality of these oocytes, or low ovarian reserve. The problem is that when you have accelerate aging, even IVF techniques can not be of great help in achieving pregnancy. The pregnancy rate (17,65%) and the childbirth rate (5,88%) with the patients older than 40 is very low, although comparable to the data from the scientific literature and speaks in favour of the fact that the success of assisted reproductive techniques is very modest with women older than 44

Bacterial Flora Play Important Roles in Acute Dextran Sulphate Sodium-Induced Colitis But Are Not Involved in Gal-3 Dependent Modulation of Colon Inflammation

An altered immune response to normal gut microflora is important for the pathogenesis of ulcerative colitis (UC). Galectin- 3 (Gal-3) is an endogenous lectin that plays an important pro-inflammatory role in the induction phase of acute colitis by promoting activation of the NLRP3 infl ammasome and production of IL-1β in macrophages. By using dextran sulphate sodium (DSS) induced colitis, a well-established animal model of UC, we determined whether Gal-3 affects the function of colon infiltrating macrophages by interfering with intestinal microfl ora. Our results showed that genetic deletion of Gal-3 significantly attenuates DSS-induced colitis by down-regulating infiltration of phagocytic cells (neutrophils, macrophages and dendritic cells) in colon tissue of DSS-treated mice, and this correlated with differences in bacterial flora of the gut. Antibiotic treatment attenuates DSS-induced colitis in WT and Gal-3-/- mice without affecting differences between the groups. In conclusion, Gram negative bacterial flora play an important role in DSS-induced acute colitis of mice but are not involved in Gal-3 dependent modulation of colon inflammation

Mesenchymal stem cells attenuate liver fibrosis by suppressing Th17 cells - an experimental study.

This study investigates molecular and cellular mechanisms involved in mesenchymal stem cell (MSC)-mediated modulation of IL-17 signaling during liver fibrosis. Mice received CCl4 (1 μl/g intraperitoneally) twice/week for 1 month. MSCs (1 × 106 ), or MSC-conditioned medium (MSC-CM), were intravenously injected 24 h after CCl4 and on every 7th day. Liver fibrosis was determined by macroscopic examination, histological analysis, Sirius red staining, and RT-PCR. Serum levels of cytokines, indoleamine 2,3-dioxygenase (IDO), and kynurenine were determined by ELISA. Flow cytometry was performed to identify liver-infiltrated cells. In vitro, CD4+ T cells were stimulated and cultured with MSCs. 1-methyltryptophan was used for inhibition of IDO. MSCs significantly attenuated CCl4 -induced liver fibrosis by decreasing serum levels of inflammatory IL-17, increasing immunosuppressive IL-10, IDO, and kynurenine, reducing number of IL-17 producing Th17 cells, and increasing percentage of CD4+ IL-10+ T cells. Injection of MSC-CM resulted with attenuated fibrosis accompanied with the reduced number of Th17 cells in the liver and decreased serum levels of IL-17. MSC-CM promoted expansion of CD4+ FoxP3+ IL-10+ T regulatory cells and suppressed proliferation of Th17 cells. This phenomenon was completely abrogated in the presence of IDO inhibitor. MSCs, in IDO-dependent manner, suppress liver Th17 cells which lead to the attenuation of liver fibrosis

Mesenchymal stem cells attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells.

Mesenchymal stem cells (MSCs) are, due to immunomodulatory characteristics, considered as novel agents in the treatment of immune-mediated acute liver failure. Although it is known that MSCs can regulate activation of T lymphocytes, their capacity to modulate function of neutrophils and natural killer T (NKT) cells, major interleukin (IL) 17-producing cells in acute liver injury, is still unknown. By using 2 well-established murine models of neutrophil and NKT cell-mediated acute liver failure (induced by carbon tetrachloride and α-galactoceramide), we investigated molecular and cellular mechanisms involved in MSC-mediated modulation of IL17 signaling during acute liver injury. Single intravenous injection of MSCs attenuate acute hepatitis and hepatotoxicity of NKT cells in a paracrine, indoleamine 2,3-dioxygenase (IDO)-dependent manner. Decreased levels of inflammatory IL17 and increased levels of immunosuppressive IL10 in serum, reduced number of interleukin 17-producing natural killer T (NKT17) cells, and increased presence of forkhead box P3 + IL10-producing natural killer T regulatory cells (NKTregs) were noticed in the injured livers of MSC-treated mice. MSCs did not significantly alter the total number of IL17-producing neutrophils, CD4+, and CD8 + T lymphocytes in the injured livers. Injection of mesenchymal stem cell-conditioned medium (MSC-CM) resulted with an increased NKTreg/NKT17 ratio in the liver and attenuated hepatitis in vivo and significantly reduced hepatotoxicity of NKT cells in vitro. This phenomenon was completely abrogated in the presence of IDO inhibitor, 1-methyltryptophan. In conclusion, the capacity of MSCs to alter NKT17/NKTreg ratio and suppress hepatotoxicity of NKT cells in an IDO-dependent manner may be used as a new therapeutic approach in IL17-driven liver inflammation. Liver Transplantation 23 1040-1050 2017 AASLD