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Mucosal malignant melanoma has a low incidence and only 2% are diagnosed in the gynecological tract. Diagnosis of primary cervical malignant melanoma is often challenging. The clinical presentation mimics other malignant cervical tumors, usually with abnormal bleeding or discharge. Cervical screening tests, such as cytology, often fail to detect malignant melanomas because of the rarity of the disorder, and histological evaluation of lesions is of paramount importance. The treatment is often based on regimens used for cutaneous malignant melanoma. We present the first case in the literature of primary malignant melanoma of the endocervix diagnosed by outpatient hysteroscopy and we have performed a narrative review of the literature on PubMed, Scopus and Web of Science from 1980 to December 2023, identifying 137 cases. The most common initial symptom was vaginal bleeding in 82.8% of cases, and 84.8% of patients were menopausal at the time of diagnosis. The first diagnostic modality was biopsy in 67.7%; 90% of patients underwent surgery and 64.5% of the deaths occurred within the first 12 months after diagnosis. Primary malignant melanoma of the cervix is extremely rare and difficult to diagnose at an early stage which is due to the aggressiveness of the disease and the non-specificity of the symptoms. To improve survival, early diagnosis is essential and hysteroscopy could be a useful tool in achieving it. It is crucial to increase the attention of gynecologists on primary malignant melanoma of the cervix to also perform a diagnostic hysteroscopy in case of doubtful symptoms.

Interstitial pregnancy is an unusual and potentially life-threatening form of ectopic pregnancy, accounting for approximately 1-6% of all ectopic pregnancies, with a maternal mortality rate of 2-2.5%. Implantation happens in the proximal portion of the fallopian tube as it passes through the myometrium. The resolution of interstitial pregnancy after medical treatment should be assessed by a decline in serum β-hCG, which occurs in about 85-90% of cases. Nonetheless, its effectiveness and consequences have been presented through case reports and case series. However, few cases of interstitial pregnancies treated totally medically with the use of methotrexate and mifepristone have been presented in the literature. Complications of this medical treatments have also never been reviewed before. In the present manuscript, we present a case of interstitial pregnancy treated with methotrexate and mifepristone. The patient after treatment developed a uterine arteriovenous malformation, treated with uterine artery embolization. Furthermore, we performed a systematic review of the literature using Scopus, PubMed and Google Scholar. A total of 186 papers were found, and 7 papers which included 10 cases were assessed for eligibility. The systemic medical treatment with the use of methotrexate and mifepristone was effective in 7 of the 10 cases. Two cases of hemoperitoneum following combined methotrexate and mifepristone treatment were reported. The applicability of this medical conservative treatment should be tailored to the patient, taking into account their obstetric history, gestational age at diagnosis and desire for future pregnancies. Complete resolution after this treatment was achieved in most of the cases reported without major complications. The appearance of uterine arteriovenous malformation can be managed conservatively, and we propose uterine artery embolization as an effective treatment of this rare complication.

(1) Background: The number of adnexal masses detected during pregnancy has increased due to the use of first-trimester screening and increasingly advanced maternal age. Despite their low risk of malignancy, other risks associated with these masses include torsion, rupture and labor obstruction. Correct diagnosis and management are needed to guarantee both maternal and fetal safety. Adnexal masses may be troublesome to classify during pregnancy due to the increased volume of the uterus and pregnancy-related hormonal changes. Management should be based on ultrasound examination to provide the best treatment. The aim of this study was to describe the ultrasound features of ovarian masses detected during pregnancy and to optimize and personalize their management with the expertise of gynecologists, oncologists and sonographers. (2) Methods: Clinical, ultrasound, histological parameters and type of management (surveillance vs. surgery) were retrospectively retrieved. Patient management, perinatal outcomes and follow-up were also evaluated. (3) Results: according to the literature, these masses are most frequently benign, ultrasound follow-up is the best management, and obstetric outcomes are not considerably influenced by the presence of adnexal masses. (4) Conclusions: the management of patients with ovarian masses detected during pregnancy should be based on ultrasound examination, and a centralization in referral centers for ovarian masses should be considered.

Recently, thanks to the greater discovery of the mechanisms of facial aging, an alternative to invasive plastic surgery has found space with less invasive aesthetic procedures, also based on an increasingly pressing request. We are specifically referring to dermal filler injection into or under the skin which leads to immediate rejuvenation and aesthetic improvements. In this study, we wanted to analyze the results obtained through the use of NEAUVIA Organic Stimulate, particularly with regard to its effectiveness, which is a cross-linked polymeric hydrogel, containing stabilized sodium hyaluronate 26 mg/mL and calcium hydroxyapatite (1%), glycine and L-proline in buffer pyrogen-free water, in its main indication, namely, the temporary correction of congenital and acquired deficiencies of the soft tissues of the face by intradermal injection. Initially, 70 patients were enrolled, but 10 did not complete the study due to non-observance of the investigation rules, so they were excluded from the protocol. The collected data demonstrate an efficient mechanical effect of the pegylated polymeric acid matrix enriched with low concertation of calcium hydroxyapatite and in accordance with other evidence in vitro and in vivo, and the mechanical support of the interstitial connective space improves the homestays of the anatomical layer rebalancing the physiological activity of the dermis cells.

The aim of this study was to test the effect of hyaluronic acid cross-linked with polyethylene glycol containing micronized portions of calcium hydroxyapatite (Neauvia Stimulate) on both local tissue and systemic consequences, which are crucial from the perspective of long-term safety, in patients suffering from Hashimoto's disease. This most common autoimmune disease is a frequently mentioned contraindication to the use of fillers based on hyaluronic acid as well as biostimulants based on calcium hydroxyapatite. Broad-spectrum aspects of histopathology were analyzed to identify key features of inflammatory infiltration before the procedure and 5, 21, and 150 days after the procedure. A statistically significant effect on the reduction of the intensity of the inflammatory infiltration in the tissue in relation to the state before the procedure was demonstrated, combined with a reduction in the occurrence of both antigen-recognizing (CD4) and cytotoxic (CD8) T lymphocytes. With complete statistical certainty, it was demonstrated that the treatment with Neauvia Stimulate had no effect on the levels of these antibodies. All this corresponds with the risk analysis that showed no alarming symptoms during the time of observation. The choice of hyaluronic acid fillers cross-linked with polyethylene glycol should be considered justified and safe in the case of patients suffering from Hashimoto's disease.

Background: Adenomyosis and congenital uterine anomalies (CUAs) can compromise reproductive potential and may coexist in the same patient, especially in cases of infertility. This review (CRD42022382850) aims to evaluate the published cases of concurrent adenomyosis and syndromic and nonsyndromic CUAs. Methods: A literature search for suitable articles published in the English language was performed using the following databases from inception to 30 November 2022: MEDLINE, EMBASE, Global Health, the Cochrane Library, Health Technology Assessment Database, and Web of Science. Articles including both CUAs and adenomyosis, with data about their potential relationship, were included. Results: The literature search retrieved 14 articles that met the purpose of this review and summarized the most recent findings regarding the concurrent diagnosis of adenomyosis and CUAs. Conclusions: Adenomyosis can be found in both syndromic and nonsyndromic CUAs, and may arise from several etiologies. The hypothesis that obstructions in CUAs increase uterine pressure and promote the development of adenomyosis remains to be further elucidated, and additional findings may also play a role. The patient's genetic, epigenetic, and hormonal patterns, as well as normal physiological processes, such as pregnancy, may influence the growth of adenomyosis.

Chorangiocarcinoma is a very rare and misdiagnosed placental neoplasm. The unique morphologic features of the lesion distinguish it from other trophoblastic tumors and vascular abnormalities. We present a systematic review of the literature to provide clarity on chorangiocarcinoma entity and biology. A literature search was carried out in December 2022 using the keywords "Placental chorangiocarcinoma", "Chorangioma", "Placenta", and "Throphoblast proliferation". Articles published from 1988 to 2022 were obtained from Scopus, Google Scholar, and PUBMED. In our review, we examined maternal age, gestational age at the time of delivery, parity, type of pregnancy, placental weight, ultrasound features of the placenta, macroscopic examination and tumor size, microscopic examination, immunostaining, maternal beta-human chorionic gonadotropin, fetal and maternal outcome. Eight manuscripts were detected. They are all case reports. The macroscopic characteristics of the lesions were represented by the presence of a grey-yellow-white color well-demarcated round nodule. Microscopically, all the authors described typical aspects of malignancy as a high rate of mitosis, nuclear atypia and necrotic areas. In some cases, the presence of AE1/AE3 cytoplasmic positivity, p63 nuclear staining, and beta-human chorionic gonadotropin (BHCG) were reported. A good fetal outcome was reported in all cases of newborns with normal birth weight, except one with fetal growth restriction. Maternal outcome was good in all cases except one with maternal lung metastasis three months after delivery. The clinical course has probably underestimated the real incidence of the pathology. Only greater knowledge of its histology and its clinical course will allow us to evaluate the real prevalence of the disease.

A high-definition mapping catheter has been introduced, allowing for bipolar recording along and across the spline with a rapid assessment of voltage, activation, and directionality of conduction. We aimed to evaluate differences in mapping density, accuracy, time, and consequently RF time between different mapping catheters used for ventricular tachycardia (VT) ablation. We enrolled consecutive patients undergoing VT ablation at our center. Patients were divided into the LiveWire 2-2-2 mm catheter (group A) and the HD Grid SE (group B). Primary endpoints were total RF delivery time, the number of points acquired in sinus rhythm and VT, and the scar area. Fifty-one patients were enrolled, 22 in group A and 29 in group B. More points were acquired in the Grid group in sinus rhythm (SR) and during VT (2060.78 ± 1600.38 vs. 3278.63 ± 3214.45, p = 0.05; 4201.13 ± 5141.61 vs. 10,569.43 ± 13,644.94, p = 0.02, respectively). The scar area was smaller in group B (Bipolar area, cm2 4.52 ± 2.72 vs. 2.89 ± 2.81, p = 0.05. Unipolar area, cm2 7.47 ± 4.55 vs. 5.56 ± 2.79, p = 0.03). Radiofrequency (RF) time was shorter in the Grid group (30.52 ± 13.94 vs. 22.16 ± 11.03, p = 0.014). LPs and LAVAs were eliminated in overall >93% of patients. No differences were found in terms of arrhythmia-free survival at follow-up. In conclusion, the use of a high-definition mapping catheter was associated with significantly shorter mapping time during VT and RF time. Significantly more points were acquired in SR and during VT. During remap, we also observed more LAVAs and LPs requiring further ablation.

The etonogestrel (ENG) implant is among the most effective reversible contraceptives. It can be a good option for patients with different chronic diseases due to no clinically significant effects on lipid metabolism or liver function. Some limitations in the use of this type of device are represented by social and psychiatric disorders, where the easy accessibility of the device becomes a negative feature. In these patients several cases of self-removal or damage to the device have been reported. We report the successful insertion of the Nexplanon ® device into the scapular region in a young woman with a chronic psychiatric disorder. To verify the presence in the literature of other possible implantation sites, we performed a systematic review of the literature on Pubmed, Google scholar and Scopus from 2000 to 2021 using different combinations of the following terms: (Nexplanon), (contraceptive implant), (insertion). Two manuscripts with three cases were detected. Nexplanon ® was implanted in the upper back. In all cases, there were no complications during the insertions and the follow up demonstrated no side effects with contraceptive efficacy. Our report and review is a further confirmation that the scapular region can become a valid insertion site, maintaining good efficacy and safety of the subcutaneous device.

Background: Provoked vestibulodynia is commonly associated with dyspareunia and affects 7% to 15% of women. This pathology has major implications on sexual function and quality of life, and several types of treatments are available for its management. However, a consensus has not been reached concerning the best treatment of vulvar pain. The aim of this study was to assess the efficacy and safety of a brand-new product, the vulvar emulgel Meclon ® Lenex, for the management of provoked vestibulodynia and non-infective vulvitis., Methods: This was a monocentric, prospective, randomized, double-blind and placebo-controlled study. We enrolled 40 women with provoked vestibulodynia; 20 patients received Meclon ® Lenex, whereas the remaining received a placebo. Each woman was assessed subjectively (through questionnaires) and objectively by evaluating vaginal and vulvar symptoms (Friedrichs criteria and Marinoff dyspareunia grade). We evaluated efficacy, safety, compliance and tolerability of the brand-new product vulvar gel Meclon ® Lenex in provoked vestibulodynia., Results: After administration of Meclon ® Lenex, we evaluated all parameters of the Friedrichs criteria (burning, dyspareunia, erythema, vulvar pain at the 5 o'clock position and 7 o'clock position), as well as the levels of Marinoff dyspareunia. The active treatment showed to be statistically significantly effective ( p value ≤ 0.05) in reducing all symptoms of Friedrichs criteria, vulvar pain and Marinoff dyspareunia., Conclusion: This prospective study showed that Meclon ® Lenex vulvar emulgel revealed an excellent tolerability and compliance, demonstrating to be a safe and effective option in the treatment of provoked vestibulodynia and non-infective vulvitis.

The COVID-19 pandemic has carried massive global health and economic burden that is currently counteracted by a challenging anti-COVID-19 vaccination campaign. Indeed, mass vaccination against COVID-19 is expected to be the most efficacious intervention to mitigate the pandemic successfully. The primary objective of the present study is to test the presence of neutralizing anti-SARS-CoV-2 antibodies (IgA and IgG) in the breast milk and sera samples from vaccinated women at least 20 days after the complete vaccine cycle. A secondary aim is to compare the IgG antibodies level in maternal serum and breast milk. The third target is to evaluate the presence of the IgG antibodies in breast milk after several weeks from the vaccination. Finally, we collected information on the health status of infants in the days following maternal vaccination. Forty-two mothers were enrolled in the study. Thirty-six received the Pfizer/BioNTech vaccine, four the Astra Zeneca vaccine, one the Moderna vaccine and another woman Astra Zeneca in the first dose and Pfizer/BioNTech in the second dose. All 42 milk samples confirmed the presence of anti-SARS-CoV-2 IgG, and none showed IgA presence. Regarding the matched 42 sera samples, 41 samples detected IgG presence, with one sample testing negative and only one positive for seric IgA. None of the 42 infants had fever or changes in sleep or appetite in the seven days following the maternal vaccination. The level of IgG antibodies in milk was, on average, lower than that in maternal serum. According to our analysis, the absence of IgA could suggest a rapid decrease after vaccination even if frequent breastfeeding could favour its persistence. IgG were present in breast milk even 4 months after the second vaccine dose. Information on the immunological characteristics of breast milk could change mothers' choices regarding breastfeeding.

Background: The incidence of infections associated with cardiac implantable electronic devices (CIEDs) and patient outcomes are not fully known., Aim: To provide a contemporary assessment of the risk of CIEDs infection and associated clinical outcomes., Methods: In Italy, 18 centres enrolled all consecutive patients undergoing a CIED procedure and entered a 12-months follow-up. CIED infections, as well as a composite clinical event of infection or all-cause death were recorded., Results: A total of 2675 patients (64.3% male, age 78 (70-84)) were enrolled. During follow up 28 (1.1%) CIED infections and 132 (5%) deaths, with 152 (5.7%) composite clinical events were observed. At a multivariate analysis, the type of procedure (revision/upgrading/reimplantation) (OR: 4.08, 95% CI: 1.38-12.08) and diabetes (OR: 2.22, 95% CI: 1.02-4.84) were found as main clinical factors associated to CIED infection. Both the PADIT score and the RI-AIAC Infection score were significantly associated with CIED infections, with the RI-AIAC infection score showing the strongest association (OR: 2.38, 95% CI: 1.60-3.55 for each point), with a c-index = 0.64 (0.52-0.75), p = 0.015. Regarding the occurrence of composite clinical events, the Kolek score, the Shariff score and the RI-AIAC Event score all predicted the outcome, with an AUC for the RI-AIAC Event score equal to 0.67 (0.63-0.71) p < 0.001., Conclusions: In this Italian nationwide cohort of patients, while the incidence of CIED infections was substantially low, the rate of the composite clinical outcome of infection or all-cause death was quite high and associated with several clinical factors depicting a more impaired clinical status.

Background: An estimated 75% of women will have one episode of vulvovaginal candidiasis (VCC) during their lifetime, and 40-50% of these will experience further episodes. The high incidence of vulvovaginal candidiasis, combined with the problems of azole resistance and toxicity, highlights the necessity for new strategies for the treatment of this condition. In this context, natural compounds represent promising alternatives. Methods: We enrolled, between January 2020 and April 2021, forty women affected by uncomplicated vulvovaginal candidiasis. Women were divided into two groups. In the first group, we treated 20 women with clotrimazole daily administration for six days. In the second group, 20 women were treated with clotrimazole associated with Unilen ® Microbio+, a new product containing Saccharomyces cerevisiae , melatonin, and GLA-14. Women underwent a check at days 15, 30, and 90. A clinical and cultural examination were performed to establish the effect of the treatments on vaginal flora. Results: In the group treated with Unilen ® Microbio+, clinical and microbiological cure at 15 and 30 days was observed in 18 women (90%), compared with 16 women (80%) in the group treated only with clotrimazole. The efficacy of the association between clotrimazole and Unilen ® Microbio+ in these uncomplicated forms was therefore not inferior to the azole treatment alone. Only four women (20%) in the Unilen ® Microbio+ group presented symptomatic recurrences within the 3 months, compared with eight women (40%) in the clotrimazole-only group. Microscopic wet mount analysis at 1 and 3 months demonstrated a significant increase in lactobacillus count and a reduction in the polymorphonucleate cells in the Unilen ® Microbio+ group. Conclusions: Unilen ® Microbio+ supplementation was demonstrated to cure uncomplicated vulvovaginal candidiasis with clotrimazole, reducing recurrence and improving vaginal flora better than clotrimazole treatment alone.

Objective: To identify the possible causes of spontaneous bladder rupture after normal vaginal delivery and to propose a diagnostic and therapeutic algorithm., Material and Methods: MEDLINE (PubMed), Web of Science and Scopus databases were searched up to August 2020. Manuscripts considered were published from 1990 and only English articles were included. The research strategy adopted included the following terms: (bladder rupture) AND (spontaneous) AND (delivery). 103 studies were identified. Duplicates were found through an independent manual screening. Subsequently, two authors independently screened the full text of articles and excluded those not pertinent to the topic. Discrepancies were resolved by consensus. Finally, thirteen studies were included., Results: PRISMA guidelines were followed. For each study, fetal weight, catheterization during labor, parity, maternal age, occurrence time, previous abdominal or pelvic surgery, symptoms complained of, diagnostic methods, and treatment were considered. Median age was 26.0 (range 20-34 years); median presentation time was 3.0 days after delivery (range 1-20 days); and median newborn weight was 3227.0 g (range 2685-3600 g). Catheterization during labor was reported only in four of the thirteen cases (30.8%) identified. The symptoms most frequently complained of were abdominal pain and distension, fever, oliguria, haematuria and vomiting. Instrumental diagnosis was performed using X-rays in five cases and computerized tomography in six cases. Ultrasound was chosen in five cases as a first diagnostic tool. In two cases, cystography was performed. Treatment was always laparotomic repair of the visceral defect., Conclusion: Abdominal pain, increased creatinine and other signs of kidney failure on blood tests should lead to suspicion of this complication. Cystourethrography is regarded as a procedure of choice, but a first ultrasound approach is recommended. The main factor for the therapeutic choice is the intraperitoneal or extraperitoneal rupture of the bladder. Classical management for intraperitoneal rupture of the bladder is surgical repair and urinary rest.

An experimental model of dryness on vaginal mucosa is proposed to assess the efficacy of a new vaginal gel (Respecta ® Hydragel Ref 17031). The dryness model was induced on reconstituted human vaginal epithelium (HVE) by incubating the tissues in modified environmental conditions (R.H. < 50% and T = 40 °C) for 48 h. The products were applied on the 'Dry' HVE models for 24 h (series 48 h + 24 h) in standard culture conditions (37 °C 5% CO 2 ). Their efficacy in counteracting vaginal dryness was assessed and compared to tissues treated with saline solution and cultured in standard culture conditions (negative control) and to untreated tissues incubated in dryness conditions for 48 h and then recovered after 24 h in standard culture conditions (positive control). The products' efficacy was quantified by measuring the following parameters: (1) water flux and direct moisturization by AQP3 immunohistochemical staining, and (2) maintenance of moisturization and elasticity of the mucosa by hyaluronic acid (CD44) immunofluorescence staining. Respecta ® Hydragel demonstrated efficacy in regulating the water flux by inducing AQP3 expression thus determining a positive water balance within the vaginal epithelium. It induced a remodelling of the epithelium morphology with restored trophism compared to the dry HVE control. Furthermore, it demonstrated a significant increase of the expression of CD44, related to hyaluronic acid (HA) distribution in the extracellular matrix. HA has the ability to act on the cellular matrix composition and its renewal compared to the dry HVE control. Through these mechanisms it induces a deep hydration and elasticity of the vaginal mucosa.

Aims: The occurrence of ventricular arrhythmias (VAs) in ischemic heart disease (IHD) patients is related to the presence and extent of fibrotic/scar tissue. As coronary atherosclerosis is the underlying cause of myocardial ischemia and fibrosis, in IHD patients implanted with an implantable cardioverter defibrillator (ICD) we investigated the relation between the VA burden and the complexity of coronary atherosclerotic lesions., Methods and Results: In IHD patients who underwent coronary angiography and ICD implant, the Syntax scores I and II (SSI-II), as index of the severity of the coronary atherosclerotic disease, and the occurrence of VA were assessed. Overall 144 patients were included (123 males). Of these 22 patients (15%) experienced at least one episode of VA (cycle length 298 ± 19 msec) that required ICD intervention. The number of episodes per patient and per year was 4 ± 6 and 2.8 ± 4, respectively. Patients that experienced a VA compared to those free from arrhythmic events did not have distinct baseline clinical characteristics except for a higher SS I and SS II (21 (IQR 13-38) vs. 16 (IQR 10-23); p = 0.037; and 50 (IQR 39-62) vs. 42 (IQR 34-50); p = 0.012). In the binary logistic regression analyses the SS I and II were the only independent predictors of VA occurrence. A higher SS II was also associated with an earlier time to first event ( p = 0.005)., Conclusion: Higher SS I-II scores reflect a more severe coronary atherosclerosis and are associated with a greater VA burden. Further studies are needed to better clarify the ability of SSI-II to stratify the risk of IHD patients to develop life-threatening VA.

Background: More and more heart failure (HF) patients aged ≥ 75 years undergo cardiac resynchronization therapy (CRT) device implantation, however the data regarding the outcomes and their predictors are scant. We investigated the mid- to long-term outcomes and their predictors in CRT patients aged ≥ 75 years., Methods: Patients in the Cardiac Resynchronization Therapy Modular (CRT MORE) Registry were divided into three age-groups: <65 (group A), 65-74 (group B) and ≥75 years (group C). Mortality, hospitalization, and composite event rate were evaluated at 1 year and during long-term follow-up., Results: Patients ( n = 934) were distributed as follows: group A 242; group B 347; group C 345. On 12-month follow-up examination, 63% of patients ≥ 75 years displayed a positive clinical response. Mortality was significantly higher in patients ≥ 75 years than in the other two groups, although the rate of hospitalizations for HF worsening was similar to that of patients aged 65-74 (7 vs. 9.5%, respectively; p = 0.15). Independent predictors of death and of negative clinical response were age >80 years, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). Over long-term follow-up (1020 days (IQR 680-1362)) mortality was higher in patients ≥ 75 years than in the other two groups. Hospitalization and composite event rates were similar in patients ≥ 75 years and those aged 65-74 (9 vs. 11.8%; p = 0.26, and 26.7 vs. 20.5%; p = 0.06)., Conclusion: Positive clinical response and hospitalization rates do not differ between CRT recipients ≥ 75 years and those aged 65-74. However, age > 80 years, COPD and CKD are predictors of worse outcomes.

Non-tubal ectopic pregnancies (NT-EPs) are rare but potentially life-threatening conditions. The incidence ranges are between 5-8.3% of all ectopic pregnancies. For this retrospective observational study, 16 patients with NT-EP and treated from January 2014 to May 2020 were recruited. Demographic details, symptoms, Beta human chorionic gonadotrophin (β-hCG) levels, ultrasound findings, management and treatment outcomes were presented. In hemodynamically stable patients, diagnosis was made using ultrasounds and β-hCG levels. Laparoscopy was essential to identify and remove the ectopic pregnancy in clinical unstable patients. A radical laparoscopic approach was chosen in one case of cervical pregnancy diagnosed late in the first trimester. Medical treatment and minimally invasive procedure, alone or combined, resulted in effective strategies in asymptomatic women with an early diagnosis of NT-EP. We report cases of cervical pregnancies successfully treated by hysteroscopy alone or combined with medical treatment, the first case of scar pregnancy treated by mini-reseptoscope and curettage and the fifth case of interstitial pregnancy treated with Methotrexate and Mifepristone. In this manuscript we report a single center experience in the management of NT-EPs with the aim of outlining the importance of the early diagnosis for a minimally invasive treatment in order to reduce maternal morbidity and mortality and preserve future fertility.

Uterine leiomyomas are benign smooth muscle cell tumors originating from the myometrium. In this study we focus on leiomyoma and normal myometrium phosphoproteome, to identify differentially phosphorylated proteins involved in tumorigenic signaling pathways, and in anti-apoptotic processes and cell survival. We obtained paired tissue samples of seven leiomyomas and adjacent myometria and analyzed the phosphoproteome by two-dimensional gel electrophoresis (2-DE) combined with immobilized metal affinity chromatography (IMAC) and Pro-Q Diamond phosphoprotein gel stain. We used mass spectrometry for protein identification and Western blotting for 2-DE data validation. Quantities of 33 proteins enriched by the IMAC approach were significantly different in the leiomyoma if compared to the myometrium. Bioinformatic analysis revealed ten tumorigenic signaling pathways and four phosphoproteins involved in both the inhibition of apoptosis and cell survival. Our study highlights the involvement of the phosphoproteome in leiomyoma growth. Further studies are needed to understand the role of phosphorylation in leiomyoma. Our data shed light on mechanisms that still need to be ascertained, but could open the path to a new class of drugs that not only can block the growth, but could also lead to a significant reduction in tumor size.