Identification of urine biomarkers of endometriosis-Protein mass spectrometry.

INTRODUCTION: Endometriosis is a chronic inflammatory disease that leads to a series of pathological reactions. The basis is a changed proinflammatory activated immune system, which results in more pronounced oxidative stress, disturbed function of proteolysis and cell apoptosis. These processes are crucial in the development of the disease because their dysfunctional activities cause the progression of the disease. It is believed that the proteins excreted in the urine interact with each other and promote pathological processes in endometriosis. METHODS: We analyzed the urine proteome of patients and aimed to detect a potential protein biomarker for endometriosis in the urine proteome. We collected urine samples from 16 patients with endometriosis and 16 patients in the control group with functional ovarian cysts. The diagnosis for all patients was confirmed through pathohistological analysis. After the preanalytical preparation of the urine, chromatography and mass spectrometry (LC-MS/MS) used the technology of urine proteome analysis. RESULTS: The main finding was a significantly different concentration of 14 proteins in the urine samples. We recorded a considerably higher concentration of proteins that have a significant role in activating the immune system (SELL), iron metabolism (HAMP) and cell apoptosis (CHGA) in endometriosis compared to controls. Proteins having an antioxidant function (SOD1) and a role in proteolysis of the extracellular matrix (MMP-9) were significantly reduced in endometriosis compared to controls. CONCLUSION: Consistent with the known pathogenesis of endometriosis, the study results complement the pathological responses that occur with disease progression.

Concentration of total proteins in urine as a non-invasive biomarker of endometriosis.

OBJECTIVE: The disease in which we observe the invasion and growth of endometrial cells on extrauterine tissues and organs with the creation of a chronic inflammatory state is called endometriosis. It causes infertility and is present in more than 30% of patients with endometriosis. Diagnosis and treatment of the disease is most often delayed for about 8 years after the first symptoms were reported. The symptomatology of endometriosis is varied, and there is no non-invasive way of diagnosis, and this is the reason for the delayed start of treatment. The development of endometriosis activates pathological processes such as the invasion and proliferation of endometriotic cells, the formation of adhesions and the activation of the immune system, which result in increased protein expression. The aim of this research is to compare the concentrations of total proteins in the urine of subjects with endometriosis with those of the control group and possibly identify a biomarker for the diagnosis of endometriosis. METHODS: Prospective urine analysis of 141 patients who were hospitalized and surgically treated at the Clinic for Gynecology and Obstetrics of KBC Rijeka from 08/21/2021 until 07/30/2022. The urine of subjects with endometriosis (N=84) and without endometriosis (n=57) was analyzed. RESULTS: Total protein in the urine is increased in the urine of subjects with endometriosis, but the total amount of protein does not correlate with the degree of disease progression. CONCLUSIONS: An increase in the level of total proteins in urine in subjects with endometriosis is a possible non-invasive diagnostic biomarker. Patients with endometriosis are grouped after the concentration of total proteins greater than 5000 µg/µl.

Proteins in urine - Possible biomarkers of endometriosis.

In the pathogenesis of endometriosis, a number of pathological reactions occur. Proteins secreted in the urine are thought to interact with each other and stimulate the pathological processes in endometriosis. Identifying one or more proteins that are specific enough and could serve as biomarkers for endometriosis is both a challenge and a necessity that would facilitate diagnosis. The urine of patients treated in a tertiary university hospital between July 1, 2020 and June 30, 2021 was analyzed. The studied group consists of patients who were treated surgically for endometriosis and in whom the diagnosis was confirmed by pathohistological analysis. The control group consists of patients who were operated for functional ovarian cysts. Urinary proteins were analyzed by chromatography and mass spectrometry (LC-MS/MS). We identified 17 proteins in urine whose concentrations were statistically significantly different in the group with endometriosis (N = 16) compared with the control groups (N = 16). The detected proteins were classified into groups according to their function in invasion, migration and proliferation, proteolysis, immune system, cell adhesion and vascular system. For all mentioned proteins the difference in concentration is statistically significant p < 0.005. Proteins are secreted in the urine of patients with endometriosis that may be involved in the pathogenesis of the disease and are possible biomarkers for endometriosis.

[Clinical recommendations for diagnosing, treatment and monitoring of patients with endometrial cancer -- Croatian Oncology Society and Croatian Society for Gynecology and Obstetrics as Croatian Medical Association units and Croatian Society of Gynecological Oncology]. / Klinicke upute za dijagnostiku, lijecienje i pracenje bolesnica oboljelih od raka maternice hrvatskoga onkoloskog drustva i hrvatskog drustva za ginekologiju i opstetriciju hrvatskoga lijecni(ckog zbora te hrvatskoga ginekoloskoonkoloskog drustva.

Uterine cancer occurs mainly in postmenopausal women, usually as vaginal bleeding. Following ovarian and cervical cancer it is the third most common cause of female reproductive system cancer death. Diagnosis is set by analyzing samples obtained via hysterectomy with salpingo-oophorectomy and pelvic / paraaortal lymphadenectomy. The following text presents the clinical guidelines in order to standardize the procedures and criteria for the diagnosis, treatment and monitoring of patients with uterine cancer in the Republic of Croatia.

[Clinical recommendations for diagnosing, treatment and monitoring of patients with ovarian cancer -- Croatian Oncology Society and Croatian Society for Gynecology and Obstetrics as Croatian Medical Association units and Croatian Society of Gynecological Oncology]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnica oboljelih od raka jajnika hrvatskoga onkoloskog drustva i hrvatskog drustva za ginekologiju i opstetriciju hrvatskoga lijetnickog zbora te hrvatskoga ginekoloskoonkoloskog drustva.

Ovarian cancer together with fallopian tube represents the fifth most common female cancer in the Republic of Croatia. Epithelial ovarian cancer, serous subtype, encompasses most of malignant ovarian neoplasms. Less common are various non-epithelial ovarian malignancies. A special group consists of epithelial carcinomas of low malignant potential with clinically indolent flow, good prognosis and no invasion, and primary cancer of the peritoneum and fallopian tube cancer. Clinically, these malignant tumors are generally asymptomatic in early stages, and usually diagnosed in advanced stages. The diagnosis is confirmed by pathological examination, and occasionally, cytological findings after completing diagnostic procedures. Multidisciplinary team makes treatment decisions, taking into account age, general condition and comorbidities of the patient and characteristics of the tumor itself, including disease stage, histological type and grade of the tumor. The principles of treatment of primary peritoneal and fallopian tube cancer are based on the principles of treatment of epithelial ovarian cancer involving surgery, chemotherapy, immune and hormone therapy, and symptomatic-supportive care throughout the treatment. Less common histological types have a different treatment approach being more frequently diagnosed in the early stages of the disease, have more indolent flow, so in these patients conservative surgeries with the goal of preserving fertility are more often employed. The following text presents the clinical guidelines in order to standardize the procedures and criteria for the diagnosis, management, treatment and monitoring of patients with ovarian carcinoma, fallopian tube and primary peritoneal cancer in the Republic of Croatia.

[Clinical recommendations for diagnosing, treatment and monitoring of patients with uterine cervical cancer -- Croatian Oncology Society and Croatian Society for Gynecology and Obstetrics as Croatian Medical Association units and Croatian Society of Gynecological Oncology]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnica oboljelih od raka vrata maternice hrvatskoga onkoloskog drustva i hrvatskog drustva za ginekologiju i opstetriciju hrvatskoga lije nickog zbora te hrvatskoga ginekoloskoonkoloskog drustva.

Cervical cancer, in comparison with other gynecological malignancies, mainly affects younger women. It can be prevented trough educational programs, screening and early detection. It also can be efficiently treated when it appears. Treatment modalities include surgery, chemotherapy and radiotherapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for the diagnosis, management, treatment and monitoring of patients with uterine cervical cancer in the Republic of Croatia.

Electrocoagulation versus suture after laparoscopic stripping of ovarian endometriomas assessed by antral follicle count: preliminary results of randomized clinical trial.

PURPOSE: The assessment of ovarian reserve by antral follicle count (AFC) following electrocoagulation versus suture after laparoscopic stripping of ovarian endometriomas. METHODS: Forty-five patients between 18 and 35 years, with unilateral endometriomas were randomly analyzed. Laparoscopic cystectomy was performed by the stripping method. Ovarian hemostasis was obtained either by suturing (group A, n = 23) or by bipolar electrocoagulation (group B, n = 22). AFC was performed by ultrasound on the third day of the three postoperative menstrual cycles. The sum of AFC was compared between sutured (A1) and electrocoagulated (B1) ovaries, as well as between intact ovaries of both groups (A0: intact ovaries in sutured group, B0: intact ovaries in electrocoagulated group). RESULTS: The median of AFC was significantly lower in operated ovaries than in intact ovaries in both groups of patients, regardless of suturing [A1 median: 12 (range 9-19) vs. A0 median: 21.0 (range 15-27), p < 0.05] or electrocoagulation [B1: 5.0 (2-10) vs. B0: 18.5 (8-29), p < 0.05]. The median AFC was significantly higher in sutured ovaries than in electrocoagulated ovaries [A1: 12 (9-19) vs. B1: 5.0 (2-10), p < 0.05]. CONCLUSION: Our preliminary data show that operation on ovarian endometriomas could reduce ovarian reserve. The AFC value suggests that the ovarian reserve was less reduced in sutured ovaries than in those electrocoagulated. Suturing as a method of hemostasis could be a better choice after stripping ovarian endometriomas.

Successful laparoscopic bipolar coagulation of a large arteriovenous malformation due to invasive trophoblastic disease: a case report.

We report the case of an acquired large arteriovenous malformation due to invasive gestational trophoblastic tumor that was treated successfully with laparoscopic surgery. After 4 cycles of methotrexate chemotherapy, a vascular tangle (volume, 28 cm(3)) was noted that emerged from the right uterine horn, invading the broad ligament adjacent to the uterine artery. Doppler ultrasonography along with magnetic resonance arteriography confirmed the diagnosis. The location, size and relation of this arteriovenous malformation to the uterine vasculature demanded urgent intervention. Laparoscopy was performed, and bipolar coagulation of the ovarian and uterine artery feeding branches was achieved after surgical resection of the tumor. The defect in the uterine wall with an intact uterine cavity was reconstructed using sutures. There were no intraoperative or postoperative complications. The patient underwent chemotherapy, and at 2-month follow-up was cured and has since had regular menstrual cycles.

Hyperreactio luteinalis could be a risk factor for development of HELLP syndrome: case report.

OBJECTIVE: To report a unique case of hyperreactio luteinalis in pregnancy associated with ovarian torsion and subsequent development of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. DESIGN: Case report. SETTING: University medical center. PATIENT(S): A 34-year-old primigravida woman with ovarian torsion in 13 weeks of pregnancy and subsequent intrauterine growth restriction (IUGR) and HELLP syndrome. INTERVENTION(S): Laparoscopic salpingo-oophorectomy due to the ovarian torsion and cesarean section (CS) due to the development of HELLP syndrome. MAIN OUTCOME MEASURE(S): HELLP syndrome. RESULT(S): In the first trimester the patient had symptoms of acute abdomen due to the ovarian torsion. Both ovaries were enlarged and multicystic. Hormonal studies confirmed an abnormally elevated level of hCG (192.000 IU/L), mild hyperthireosis, and hyperandrogenemia. Laparoscopic salpingo-oophorectomy was performed. At 30 weeks of pregnancy, IUGR was confirmed sonographically and clinically, and at 33 weeks severe preeclampsia developed. One week later, HELLP syndrome occurred. Emergency CS was preformed, and she delivered a female newborn weighing 1,640 g. Seven days after delivery, blood pressure and hormonal status returned to normal. CONCLUSION(S): Hyperreactio luteinalis due to the abnormally high level of hCG in the first trimester could be a consequence of inappropriate trophoblast invasion and an early sign of subsequently developing preeclampsia, eclampsia, and HELLP syndrome.

Ovarian cancer: PCD and brain metastases.

Paraneoplastic cerebellar degeneration (PCD), the one of the most common paraneoplastic syndromes, refer to clinical disorders associated mostly with lung, ovarian and breast cancer, but not directly caused by the cancer or its metastases. Pathologic finding is an extensive loss of Purkinje cells in the cerebellum. Immunohistochemically, the auto-antibodies on the Purkinje cells had been detected. Clinically, PCD is characterized by sub-acutely evolving pancerebellar symptoms. Neurological dysfunction may appear before the detection of the underlying cancer. Therefore, the surgical exploration is necessary for the final diagnosis. The patient undergoes specific therapy. Soon, neurological status of the patient gets irreparable worse. Death come usually 2-3 years after the first symptoms of the PCD occurs. Case of a 63-years old woman with PCD as the first evidence of her cancer is reported. The patient developed brain metastases and died almost 3 years after the first symptoms of PCD occur

Laporovaginal surgery in cervical cancer: a Croatian experience.

With correct staging a large number of patients with cervical cancer FIGO stages IA2 and IB can be spared of unnecessary radiation therapy by laparoscopic assisted vaginal radical hysterectomy (LAVRH) as an option of radical surgical treatment in such patients. The development of laparovaginal surgery, indication and contraindication were presented. Also, the surgical technique was described in detail. Fifty-two patients were followed up in 2003 after LAVRH or open surgery, performed in our single center. Only 5 (14%) patients died from cervical cancer within 3 years following the treatment. They were all clinical stage IB treated with open surgery. There were 4 (11%) complications following treatment and they were all in patients with clinical stage IB, also treated with open surgery. There was no complication in LAVRH treated patients. The results and complications of the sole Croatian center performing LAVRH or open surgery in patients with cervical cancer FIGO stages IA and IB were similar to those in centers across the world.

Laparoscopic approach to interstitial pregnancy.

CASE REPORT: A successful laparoscopic management of an interstitial pregnancy of 42-year-old woman, treated by cornual resection was presented. The patient had an unremarkable postoperative course. DISCUSSION: The laparoscopic approach toward cornual pregnancy was presented as well as its advantages over classic laparotomy. Other techniques of conservative treatments have been reviewed.