The effect of adjuvant mitotane therapy of the adrenocortical carcinoma on the endometrium and its clinical consequences in menstruating women. Literature review and authors' own experiences.

Adrenocortical carcinoma (ACC) is a malignant tumour that originates from the adrenal cortex. It is a highly aggressive cancer characterised by a poor prognosis with an annual incidence estimated to be up to 2 cases per million. In the adult population, ACC is diagnosed typically between 40 and 50 years of age, more often in women. Complete surgical resection of the tumour is the primary treatment method for ACC. Unfortunately, despite properly performed adrenalectomy, regional recurrences or distant metastases are detected in up to 90% of the patients. For that reason, adjuvant therapy is recommended. Mitotane is the most effective adrenal-specific agent used in adjuvant and palliative therapy. Two menstruating patients, after adrenalectomy due to ACC, during adjuvant mitotane therapy, have been included in the study. The study aimed to assess the effect of mitotane therapy on the endometrium and its clinical consequences, based on the analysis of these two cases and a review of the literature. It seems that menorrhagia may be expected during adjuvant mitotane therapy of ACC in menstruating women. Heavy uterine bleeding during menstruation may appear several months after the beginning of therapy. The likely mechanism for heavy menstrual bleeding is complex. Menorrhagia can occur due to the toxic effect of mitotane in the form of a haemorrhagic diathesis, while long-term treatment (over ten months) can lead to relative hypoestrogenism resulting in endometrial hyperplasia. Clinical signs of hypoestrogenism during mitotane treatment, have been described (including pre-puberty girls) and should be considered as a side-effect of the therapy. Menorrhagia may lead to severe anaemia, so this should be considered when planning mitotane treatment. Continuous gestagen therapy is helpful in the treatment of the above disorders. After over 60 years of experience with mitotane usage, knowledge about it is still insufficient, and further studies are required.

Noninvasive diagnostic imaging of pelvic venous disorders.

It is estimated that chronic pelvic pain (CPP) may affect up to 24% of women. Unfortunately, very often, despite extensive diagnostics, the cause of CPP remains unknown. The pathophysiology of CPP could be explained to a large extent by the occurrence of pelvic venous disorders (PVD). Although pelvic venography is still considered the gold standard for the diagnosis of PVD, noninvasive diagnostic imaging techniques seem to be instrumental in the initial identification of patients with PVD. This literature review aimed to analyze and evaluate the usefulness of noninvasive diagnostic imaging techniques like transvaginal ultrasonography, transabdominal ultrasonography, magnetic resonance, and computed tomography in the diagnosis and identification of patients with PVD. Forty-one articles published between 1984 and 2023 were included in this literature review. Based on this literature review, we conclude that the clinical application of noninvasive diagnostic techniques in the diagnosis of PVD seems to be very promising. Future studies investigating the role of noninvasive diagnostic imaging techniques in the diagnosis of PVD are required.

The Lublin Protocol of the Uterine Arteries Embolization in the Treatment of Symptomatic Uterine Fibroids.

Uterine fibroids are benign tumors originating from smooth muscle tissue, constituting uterine muscle stroma. Uterine fibroids are the most common benign tumors found in women. In 20%-50% of women, fibroids are asymptomatic and do not require any treatment. The main symptoms of uterine fibroids are profuse menstrual bleeding, abnormal uterine bleeding, and pressure symptoms. Pressure symptoms can cause pelvic pain syndrome, urination disorders, and constipation. The treatment methods that are currently used include surgical treatment, pharmacological therapy, and minimally invasive procedures. The most commonly applied minimally invasive method is the embolization of uterine arteries. This procedure is currently a widely accepted method of treatment for symptomatic uterine fibroids and has been recognized as such by the National Institute for Health and Clinical Excellence in the guidelines for heavy menstrual bleeding. This is a complicated procedure and requires close cooperation between gynecologists and interventional radiologists. We present a protocol applicable to uterine artery embolization in the treatment of symptomatic uterine fibroids. The protocol is divided into five section. The first two section are intended for gynecologists and interventional radiologists, explaining how to qualify and prepare a patient for embolization in a step-by-step manner. Section three, which is directed at interventional radiologists, explains how embolization should be done. Section four is directed at gynecologists or hospital ward doctors who look after the patients after embolization. This section of the protocol offers a method for treating post-embolization pain using the Patient Controlled Analgesia (PCA) pump. Section five completes the procedure with an assessment of the effects and late complications of uterine artery embolization. All five section create a uniform protocol directed at clinicians, experts, and researchers new to the field.

Green urine sign after laparoscopic chromopertubation as an effect of severe contrast intravasation: a report of three cases.

Tubal diseases are responsible for 25% to 35% of female infertility. Laparoscopic chromopertubation is the gold standard for assessing tubal patency when female infertility is suspected. Intravasation is a complication of intrauterine procedures involving the passage of fluid filling the uterine cavity into the bloodstream through endometrial vessels (from the myometrial veins to the uterine venous plexuses). This complication has been described during hysterosalpingography and sonohysterosalpingography. We herein present a report of three cases in which severe intravasation occurred during laparoscopic chromopertubation using methylene blue as a contrast agent. The intravasation manifested as green urine (i.e., the "green urine sign"). The presence of methylene blue in the urine and blood was confirmed by laboratory tests. All three patients had risk factors for intravasation as described in the literature (unilateral or bilateral tubal obstruction, endometriosis, and previous intrauterine procedures for Mullerian duct anomalies and Asherman's syndrome). The green urine sign appeared a few hours after laparoscopic chromopertubation and spontaneously resolved after 24 hours. Cystoscopy was performed to rule out bladder injury. All three patients required only clinical observation.

Psychological aspects of infertility. A systematic review.

OBJECTIVE: Fertility may be defined as a capacity to conceive and produce offspring. Infertility is characterized by failure to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse. Infertility concerns an estimated 8-12% of the global population, and is associated with factors including time of unwanted non-conception, age of female partner and number of diseases impacting fertility. Unexplained infertility is described as idiopathic. This study aimed to analyse and evaluate the influence of mental disorders, often considered as reasons for idiopathic infertility, on female and male fertility, including stress, depression, sleep and eating disorders, and addictions. METHODS: This systematic review comprised a search of MEDLINE, Cochrane and PubMed databases for relevant articles that were analysed by two independent reviewers. RESULTS: A total of 106 articles published between 1955-2019 were included. Mental disorders modify endocrine gland and immune system functioning at both the tissue and cellular level, and are negatively associated with female and male fertility. CONCLUSION: Mental disorders may negatively impact female and male fertility. Further studies are required to explain the exact role and contribution of mental disorders to fertility.

The role of the "beret" sign and other markers in ultrasound diagnostic of the acrania-exencephaly-anencephaly sequence stages.

INTRODUCTION: Neural tube defects (NTDs) are a group of heterogeneous congenital anomalies of the central nervous system (CNS). Acrania is a non-NTD congenital disorder related to the CNS. It can transform into anencephaly through the acrania-exencephaly-anencephaly sequence (AEAS). In AEAS, the cerebral tissue is not protected and is gradually destroyed due to exposure to the harmful effect of amniotic fluid and mechanical injuries. These lead to exencephaly and then into anencephaly. In contrast to primary anencephaly (NTDs), this type of anencephaly authors suggests calling secondary anencephaly. OBJECTIVE: Analysis of the known prenatal ultrasonography (US) signs associated with AEAS. Simultaneously, the authors propose a new sign in the differentiation of acrania from exencephaly and anencephaly, called the "beret" sign. METHODS: It is a two-centre retrospective observational study. As part of the study, 4060 US scans were analyzed. RESULTS: In 10 cases, the absence of calvarium was diagnosed, allowing recognition of either AEAS stages or primary anencephaly. In 5 cases, cerebral structures were enclosed by an inertial rippled thin membrane, with a smooth outer contour. Between the described membrane and the brain structures, a thin anechoic space corresponding to cerebrospinal fluid was observed. This sign was defined as the "beret" sign. In these cases, acrania was diagnosed. In three cases calvarium was missing. The brain structures had an irregular appearance, did not wave and remained motionless. The outer contour was unequal as if divided into lobes. Amniotic fluid was anechoic. Exencephaly was diagnosed in these cases. In two cases calvarium, brain structures, and meninges were missing. The "frog eyes" sign and slightly echogenic amniotic fluid were visible. In this case, anencephaly was diagnosed. CONCLUSIONS: The "beret" sign seems to be a promising tool in the diagnosis of acrania. Furthermore, echogenicity of amniotic fluid could be useful during differentiation between primary and secondary anencephaly.

Is it necessary to correct a caesarean scar defect before a subsequent pregnancy? A report of three cases.

Rates of caesarean section have increased over recent years and so too have associated complications, one of which is a caesarean scar defect (CSD). The defect may cause gynaecological symptoms, such as menometrorrhagia, infertility, chronic abdominal/pelvic pain or it may be asymptomatic. The presence of CSD may lead to obstetrical sequalae such as preterm delivery, uterine rupture, caesarean scar pregnancy or abnormal placenta implantation. Three cases of CSD are described here. In one case, surgical correction of the CSD was performed before a subsequent pregnancy with an uncomplicated obstetric outcome. In the other two cases, surgical correction of the CSD was not performed and the pregnancies were complicated by caesarean scar dehiscence and caesarean scar pregnancy. We suggest that women with a CSD may benefit from surgical correction of the defect before becoming pregnant to reduce the likelihood of serious complications.

Ascites Index - an attempt to objectify the assessment of ascites.

INTRODUCTION: Ascites is observed in cancer patients as well as in other non-neoplastic processes. In some patients, it may cause severe symptoms that can become directly life-threatening. The assessment of the degree of ascites seems useful in the determination of treatment effects as well as in the monitoring of fluid accumulation and early planning of decompression procedures. AIM: Determination of the clinical usefulness of a quantitative method of determining the degree of ascites, so-called Ascites Index. MATERIAL AND METHODS: The Ascites Index is an ultrasonographic way of assessing the grade of ascites. The examination result is an index which is analogous to the amniotic fluid index determined in pregnant patients. The Ascites Index was determined in patients with ascites in the course of stage III-IV ovarian carcinoma (7 patients) and ovarian hyperstimulation syndrome (12 patients). RESULTS: The patients with ovarian hyperstimulation syndrome required decompressive paracentesis at the median Ascites Index above 290 mm (range: 216-386 mm). In the patients with ovarian carcinoma, the median value of the Ascites Index at which paracentesis was required was 310 mm (range: 273-389 mm). To avoid complications associated with excessive protein loss, 2000 mL of fluid was evacuated at a single occasion. Following the procedure, the median value of the Ascites Index was 129 mm (range: 121-145 mm) in the patients with ovarian hyperstimulation syndrome and 146 cm (119-220 mm) in cancer patients. CONCLUSIONS: The proposed index is simple and rapid to determine. It makes evaluation of the degree of ascites considerably easier. Moreover, it only minimally burdens patients and enables assessment of the effect of decompression or treatment. It seems that this method might be useful also in the assessment of ascites caused by other factors, but this requires further clinical studies.

Ascites Index - a novel technique to evaluate ascites in ovarian hyperstimulation syndrome: a concept-proof study.

OBJECTIVES: Controlled ovarian hyperstimulation is an important step in infertility treatment. In some cases, however, ovar-ian hyperstimulation syndrome (OHSS) can occur. In its severe forms, ascites is likely to develop, associated with dyspnea. The aim of this study was to explore the usefulness of Ascites Index (AsI), a new tool for quantitative determination of ascites in patients with OHSS, to obtain data for planning further trials. MATERIAL AND METHODS: Twelve patients with OHSS and ascites were included in the study. All patients were admitted to the hospital because of abdominal pain and dyspnea due to increasing ascites. Ultrasound measurements of ascites extent were performed in four external quadrants of the abdomen. Pockets of free fluid were measured. The obtained values were totaled, forming the Ascites Index (AsI), similarly to the amniotic fluid index. Because of dyspnea, paracentesis was performed in all cases. RESULTS: Median AsI at which patients reported dyspnea was 29.0 cm (range 21.6-38.6 cm). At AsI values less than 21.6 cm, no dyspnea was observed in any of the 12 studied patients. To avoid complications, 2000 mL of ascitic fluid was collected in each patient. After paracentesis, range of AsI decreased to 12.1-14.5 cm. CONCLUSIONS: The proposed AsI seems to be a promising tool for estimating and monitoring the ascites extent in OHSS. It can be estimated using basic ultrasound equipment. AsI requires further studies for standardization and transferability to other causes of ascites.

Use of a levonorgestrel-releasing intrauterine device for menorrhagia treatment during adjuvant therapy of adrenocortical carcinoma with mitotane.

Adrenocortical carcinoma is a rare tumour with high malignancy and poor prognosis. This tumour is rarely diagnosed in the reproductive age. Complete surgical resection is the only curative treatment for adrenal cancer in all stages. After surgery adjuvant chemotherapy is required. Mitotane is the most important drug in adrenal cancer chemotherapy. Mitotane's mode of action is not entirely explained. Animal studies have shown that the substance exerts a direct cytotoxic effect on the cells of the adrenal cortex. This activity is selective, progressive and affects only the zona reticularis and fasciculata of the adrenal cortex. Mitotane inhibits cortisol synthesis by disrupting the chain of cholesterol. It has been suggested, that mitotane also affects the peripheral metabolism of steroids, especially of transcortin (CBG). This results in an increase of CBG blood concentration and a reduction of the amount of free hormones.

Minimally invasive procedures in the management of uterine fibroids.

Uterine fibroids are benign uterine tumors. In women during the reproductive period, uterine fibroids occur in about 25%, whereas after this time, they are observed in more than 40% of women. In the majority of women (about 20-50%), such tumors do not cause discomfort and do not require treatment. Asymptomatic uterine fibroids usually undergo only regular medical control, whereas symptomatic fibroids are an indication for treatment. Current treatment methods include surgical, pharmacological and minimally invasive treatment. Among the current commonly used methods, there are minimally invasive treatment options, which include Uterine Artery Embolization (UAE), Magnetic Resonance Guided Ultrasound Surgery (MRgFUS), MR-guided High Intensity Focused Ultrasound (MR-HIFU) and Laparoscopic Uterine Artery Occlusion (LUAO). The minimally invasive Ultrasound-guided High Intensity Focused Ultrasound method (US-HIFU) is new, but still experimental. The use of MRgFUS/MR-HIFU for the thermoablative treatment of fibroids was approved by the FDA (Food and Drug Administration) in 2004. As a minimally invasive method, it enables preservation of the uterus and eliminates the need for general anesthesia. LUAO is based on the use of the vascular clip, which is placed on the uterine artery at the level of the internal iliac artery. This procedure is performed bilaterally. The use of UAE in obstetrics and gynecology was first described in 1987 as an effective method in the treatment of hemorrhage, which allows avoiding surgical intervention and enables the uterus to be preserved. An appropriate qualification of patients is crucial for high clinical efficacy and prevention of complications after UAE. The candidates should be women with symptomatic uterine fibroids, without other pathologies within the pelvis, who do not plan to get pregnant in the future. The variety of uterine fibroids as for the location, size, and symptoms they can evoke, has enforced a very individual approach to each patient, to begin with observation and regular gynecological control, through a number of pharmacological and minimally invasive treatment methods, and ending with the removal of the uterus. It gives the doctors the tools, which, if used properly, can manage uterine fibroids and fulfil the expectations of the patient.