MRI of endometriosis in correlation with the #Enzian classification: applicability and structured report.

Endometriosis represents one of the most common causes of life-impacting chronic pelvic pain and female infertility. Magnetic resonance imaging (MRI) plays an increasing role in the diagnosis and mapping of endometriosis, while diagnostic laparoscopy currently tends to be reserved for the patients with negative imaging results. The #Enzian, published in 2021, proposes a new comprehensive classification system of endometriosis, combining a complete staging of deep infiltrative endometriosis with the evaluation of peritoneal/ovarian/tubal localizations and the presence of adenomyosis. This article addresses in detail the applicability of the #Enzian classification, primarily based on surgical findings, to the MRI evaluation of the endometriosis. Overall, there is a significant matching between MRI features and the #Enzian classification criteria, two different perspectives of endometriosis mapping, with different goals and levels of detail. The main discrepancy lies in the evaluation of tubo-ovarian condition, which is not fully assessable by MRI. Furthermore, as endometriosis is a complex disease, usually multifocal, that can present with a myriad of imaging findings, MRI reporting should be clear and well organized. The authors group, both radiologists and gynecologists, propose a structured MRI report of endometriosis in correlation with the #Enzian classification, merging the detailed anatomical and pre-operative information provided by the MRI with the benefits of a comprehensive classification system of endometriosis in the clinical practice and research field.Critical relevance statement This article addresses in detail the applicability of the #Enzian classification, primarily based on surgical findings, to the MRI evaluation of the endometriosis and proposes a #Enzian-based structured MRI report.

Hysteroscopic myomectomy: The guidelines of the International Society for Gynecologic Endoscopy (ISGE).

OBJECTIVE: With this publication, the International Society for Gynecologic Endoscopy (ISGE) aims to provide the clinicians with the recommendations arising from the best evidence currently available on hysteroscopic myomectomy (HM). STUDY DESIGN: The ISGE Task Force for HM defined key clinical questions, which led the search of Medline/PubMed and the Cochrane Database. We selected and analyzed relevant English-language articles, published from January 2005 to June 2021, including original works, reviews and the guidelines previously published by the European Society for Gynecological Endoscopy (ESGE) and the American Association of Gynecologic Laparoscopists (AAGL), in which bibliographies were also checked in order to identify additional references, using the medical subject heading (MeSH) term "Uterine Myomectomy" (MeSH Unique ID: D063186) in combination with ''Myoma" (MeSH Unique ID: D009214) and ''Hysteroscopy" (MeSH Unique ID: D015907). We developed the recommendations through multiple cycles of literature analysis and expert discussion. RESULTS: The ISGE Task Force did develop 10 grade 1A-C and 4 grade 2A-C recommendations. For planning HM, evaluation of the uterus with saline infusion sonohysterography (SIS) or combined assessment by transvaginal ultrasound (TVUS) and diagnostic hysteroscopy is recommended (Grade 1A). The use of STEPW (Size, Topography, Extension of the base, Penetration and lateral Wall position) classification system of submucosal leiomyoma (LM) is recommended to predict the complex surgeries, incomplete removal of the LM, long operative time, fluid overload and other major complications (grade 1B). For type 0 LMs, in addition to resectoscopy (slicing technique), morcellation is recommended, being faster and having a shorter learning curve with respect to resectoscopy (grade 1C). For type 1-2 LMs, slicing technique is currently recommended (grade 1C). A fluid deficit of 1000 mL also in case of bipolar myomectomy with saline solution, in healthy women of reproductive age, contains low risk for major complications. Lower thresholds (750 mL) for fluid deficit should be considered in the elderly and in women with cardiovascular, renal or other co-morbidities (Grade 1B). CONCLUSION: HM is the most effective conservative minimally invasive gynecologic intervention for submucous LM. The set of 14 ISGE recommendations can significantly contribute to the success of HM and the safety of patients for whom the choice of appropriate surgical technique, as well as the surgeon's awareness and measures to prevent complications are of the utmost importance.

A randomized control trial comparing vaginal and laparoscopically-assisted vaginal hysterectomy in the absence of uterine prolapse in a South African tertiary institution.

OBJECTIVES: The primary objectives of this study were to estimate blood loss, operation time and cost differences in patients undergoing vaginal hysterectomy (VH) versus laparoscopically-assisted vaginal hysterectomy (LAVH). The secondary objectives were to determine differences in hospital stay, need for postoperative analgesia, intra- and immediate post-operative complications, and the rate of conversion to laparotomy. VH was hypothesized to be the preferred route for hysterectomy for benign uterine conditions. STUDY DESIGN: A randomized control study was undertaken at the Department of Obstetrics and Gynaecology of the Charlotte Maxeke Johannesburg Academic Hospital and included the women admitted between January 2017 and December 2019 for hysterectomy due to benign conditions, meeting the inclusion criteria (vaginally accessible uterus, estimated uterine size ≤ 12 weeks of gestation or ≤ 280 g on ultrasound examination and pathology confined to the uterus). Surgical procedures were performed by the residents in training under the supervision of specialists with large experience. The patient demographic characteristics, uterine weight, operative time, estimated blood loss(expressed as the difference between preoperative and postoperative day one serum haemoglobin),direct surgery-associated costs, intra- and immediate post-operative complications and the length of hospital stay were recorded and comparatively analysed among patients randomly placed in VH and LAVH group. RESULTS: A total of 227 women were included (151 patients underwent VH and 76 LAVH, upon 2:1 randomization, performed on this way to reflect the previous pattern of operating of the unit). The patients were matched with respect to age, parity and body mass index. No significant differences between two groups were found in mean uterine weight and also in mean serum haemoglobin shift, intra- and immediate post-operative complications, and convalescence period duration. There were statistically significant differences in operating time and in cost between the two procedures. On average, LAVH took longer than VH to be performed (62.8 ± 9.3 vs 29.9 ± 6.6 min, p < 0.0001) and it was more costly, mainly due to the longer operating time and required disposables. An amount of 15698.20 South African Rand (ZAR) or 1145.85 United States Dollar (USD) more were needed to perform LAVH in comparison to VH. All VHs and LAVHs were successfully accomplished without major complications or conversation to laparotomy. CONCLUSION: Our data indicate that VH is a feasible and safe alternative for a large group of women with benign pathology and non-prolapsed uteri, being a faster and less costly procedure than LAVH.

Conservative Management of Asymptomatic Adnexal Masses Classified as Benign by the IOTA ADNEX Model: A Prospective Multicenter Portuguese Study.

This prospective multicentric study aiming to determine the incidence of complications (malignant transformation, torsion or rupture) during conservative management of adnexal masses was performed in two Portuguese tertiary referral hospitals. It included ≥18-year-old, non-pregnant patients with asymptomatic adnexal masses (associated IOTA ADNEX risk of malignancy < 10%) sonographically diagnosed between January 2016 and December 2020. Conservative patient management consisted of serial clinical and ultrasound assessment up to 60 months of follow-up, spontaneous resolution of the formation or surgical excision (median follow-up: 17.8; range 9-48 months). From the 573 masses monitored (328 premenopausal and 245 postmenopausal adnexal masses), no complications were observed in 99.5%. The annual lesion growth rates and increases in morphological complexity were similar in the premenopausal and postmenopausal patients. Spontaneous resolution, evidenced in 16.4% of the patients, was more common in the premenopausal group (p < 0.05). Surgical intervention was performed in 18.4% of the cases; one borderline and one invasive FIGO IA stage cancer were diagnosed. There was an isolated case of ovary torsion (0.17%). These data support conservative management as a safe option for sonographically benign, stable and asymptomatic adnexal masses before and after menopause and highlight the need for expedite treatment of symptomatic or increased-morphological-complexity lesions.

Structured report for dynamic ultrasonography in patients with suspected or known endometriosis: Recommendations of the International Society for Gynecologic Endoscopy (ISGE).

OBJECTIVE: The International Society for Gynecologic Endoscopy (ISGE) developed this project to establish the recommendations for structured reporting of dynamic ultrasound findings, promoting on this manner the practice of standardized, comprehensive and systematic evaluation and reporting of endometriosis in pelvic structures, in correlation with the #Enzian classification. STUDY DESIGN: A non-systematic review was done through a search on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), Health Technology Assessment Database and Web of Science, using the medical subject heading (MeSH) term "endometriosis" (MeSH Unique ID: D004715) in combination with "diagnostic imaging" (MeSH Unique ID Q000000981) and "consensus" (MeSH Unique ID D032921). The information extracted from the articles of interest, written in English and published from inception of the above-mentioned databases until May 2021, was graded by the level of evidence using the American College of Chest Physicians (ACCP) classification system. The recommendations for a structured reporting of ultrasound findings were developed through multiple cycles of literature analysis and expert discussion following the Delphi method. RESULTS: The ISGE recommends the adoption of the terms, definitions and methods proposed by the International Deep Endometriosis Analysis (IDEA) Group for ultrasound assessment of patients with suspected or known endometriosis (grade 1C), since this is the most comprehensive and systematic concept currently available. This paper provides the ISGE structured reporting template for presenting quantitative and qualitative information upon the IDEA consensus-based sonographic assessment of the uterus, adnexa, anterior and posterior compartment. The #Enzian classification is recommended to summarize the findings in a standard fashion (grade 1B). CONCLUSION: Mapping of pelvic endometriosis by ultrasound is accurate when trained sonographers perform the technique. Structured reporting of the lesions may improve patient counseling and treatment planning, including the organization of multidisciplinary teams and the selection of the most appropriate medical or surgical therapeutic strategy.

Invasive mole presenting as a heavily bleeding vaginal lesion 3 weeks after uterine evacuation.

Gestational trophoblastic disease occurs in 1-3:1000 gestations worldwide. Up to one-fifth of complete hydatidiform moles undergo malignant transformation, with 2%-4% manifesting as metastatic disease. Of these, a third present with vaginal metastases, which can cause bleeding and discharge. We describe the case of a 49-year-old primiparous woman presenting with syncope and intense bleeding from an anterior vaginal lesion, 3 weeks after uterine evacuation for a presumed spontaneous abortion. A vaginal metastatic nodule was suspected; haemostasis was achieved with vaginal packing, precluding the need for surgical intervention. The patient was ultimately diagnosed with invasive mole with vaginal and lung metastases (stage III high-risk gestational trophoblastic neoplasia (GTN)) and started on multiple-agent chemotherapy. Two months later the lesion had regressed completely, and remission was reached 2 weeks later. Clinicians should consider the possibility of metastatic GTN with vaginal involvement whenever heavy vaginal bleeding follows a recent history of failed pregnancy.

Low-grade mucinous appendiceal neoplasm mimicking an ovarian lesion: A case report and review of literature.

BACKGROUND: Appendiceal tumors are rare lesions that may not be easily differentiated from primary ovarian lesions preoperatively, despite the use of advanced diagnostic methods by experienced clinicians. CASE SUMMARY: A 59-year-old G2P2 woman, with chronic pelvic pain, underwent a pelvic ultrasound that revealed an adnexal mass measuring 58 mm × 34 mm × 36 mm, with irregular borders, heterogeneous echogenicity, no color Doppler vascularization and without acoustic shadowing. Normal ovarian tissue was visualized in contact with the lesion, and it was impossible to separate the lesion from the ovary by applying pressure with the ultrasound probe. Ascites, peritoneal metastases or other alterations were not observed. With the international ovarian tumor analysis ADNEX model, the lesion was classified as a malignant tumor (the risk of malignancy was 27.1%, corresponding to Ovarian-Adnexal Reporting Data System category 4). Magnetic resonance imaging confirmed the presence of a right adnexal mass, apparently an ovarian tumor measuring 65 mm × 35 mm, without signs of invasive or metastatic disease. During explorative laparotomy, normal morphology of the internal reproductive organs was noted. A solid mobile lesion involved the entire appendix. Appendectomy was performed. Inspection of the abdominal cavity revealed no signs of malignant dissemination. Histopathologically, the appendiceal lesion corresponded to a completely resected low-grade mucinous appendiceal neoplasm (LAMN). CONCLUSION: The appropriate treatment and team of specialists who should provide health care to patients with seemingly adnexal lesions depend on the nature (benign vs malignant) and origin (gynecological vs nongynecological) of the lesion. Radiologists, gynecologists and other pelvic surgeons should be familiar with the imaging signs of LAMN whose clinical presentation is silent or nonspecific. The assistance of a consultant specializing in intestinal tumors is important support that gynecological surgeons can receive during the operation to offer the patient with intestinal pathology an optimal intervention.

Formal institutional guidelines promotes the vaginal approach to hysterectomy in patients with benign disease and non-prolapsed uterus.

OBJECTIVES: This study was undertaken at the Department of Obstetrics and Gynaecology of the Charlotte Maxeke Johannesburg Academic Hospital to determine if the use of formal guidelines and a standardised surgical technique would increase the rate of vaginal hysterectomy (VH) and result in an overall decline in open abdominal hysterectomy (AH). STUDY DESIGN: All women admitted between July 2001 and December 2014 for hysterectomy due to benign conditions, meeting the guidelines criteria (vaginally accessible uterus, uterus ≤ 12 weeks size or ≤ 280 g on ultrasound examination and pathology confined to the uterus) were included. The surgical route was determined using the Unit surgical decision tree algorithm. In cases where the pathology was not confined to the uterus or success in VH was uncertain, laparoscopic assisted vaginal hysterectomy (LAVH) was performed. The VH procedures were performed by the residents in training, under the supervision of specialists with large experience in vaginal surgery. In addition to the patient characteristics and surgical approach to hysterectomy, length of hospital stay, intra-operative and immediate post-operative complications were also recorded and analysed. RESULTS: A year before the initiation of the study, the percentage of all VHs undertaken in the Department was 9.8 % (mainly performed for utero-vaginal prolapse). During the study period, 1143 vaginal procedures (1017 VHs and 126 LAVHs) were performed. The most common indications were cervical dysplasia, uterine fibroids, dysmenorrhoea or abnormal uterine bleeding, adenomyosis, endometrial hyperplasia and chronic pelvic pain. Introducing a formal clinical decision tree algorithm and a standardised surgical technique resulted in an increase in the rate of VH to 48.4 % and overall decline in open AH from 91.2%-51.6%. Thus, the VH/AH ratio increased from 1/9 at the beginning of the study (July 2001) to 1/1 by its end (December 2014). In all cases, VH was performed without the need to convert the vaginal to the abdominal route. CONCLUSION: The use of institutional guidelines for determining the hysterectomy route and a standardised VH technique resulted in an increased number of performed VHs. This provided an essential opportunity for residents to acquire, improve and maintain the skills required to safely perform VH.

Impaired inflammatory state of the endometrium: a multifaceted approach to endometrial inflammation. Current insights and future directions.

New insights into the complex and fine-regulated inflammatory mechanisms involved in the endometrium reveal multiple facets to the problem of endometrial inflammation. However, the entity termed chronic endometritis is to date restricted to infectious etiology and managed with antibiotics. Conversely, the concept of impaired inflammatory state of the endometrium (IISE) provides a more global approach to defective endometrial inflammation, considering both infectious and non-infectious etiology. A non-systematic review was done through a search on MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database and Web of Science, research registers. Pertinent original and review articles, published in English or French until December 31, 2019, were selected. A compelling body of evidence demonstrates transient, repeated and persistent IISE to be a major factor of most problematic disorders in obstetrics/gynecology, such as endometrial polyps, unexplained infertility, miscarriage, placenta-related pathology and endometrial cancer. When scheduled accordingly, hysteroscopy can play a key role in the IISE assessment. Robust data suggests the pertinence of minimal-effective anti-inflammatory regimens for therapeutic IISE targeting. This review provides a comprehensive update on the multiple facets of inflammation in the endometrial physiology and pathology. Further research is needed to improve classification, diagnosis and treatment of IISE.

Evidence-based practical guidelines of the International Society for Gynecologic Endoscopy (ISGE) for vaginal hysterectomy.

OBJECTIVE: The study was established by the International Society for Gynecologic Endoscopy (ISGE) to provide evidence-based recommendations in the steps that should be undertaken in successfully performing a vaginal hysterectomy for a non-prolapsed uterus. MATERIAL AND METHODS: The ISGE Task Force for vaginal hysterectomy for the non-prolapsed uterus defined key clinical questions regarding the surgical technique, which led the Medline/PubMed and the Cochrane Database literature search. Identified pertinent articles, published in English from 1997 to 2019, were analysed. The available information was graded by the level of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach. The recommendations were developed through multiple cycles of literature analysis and expert discussion. RESULTS: Six recommendations were established: 1. A circular incision at the level of cervico-vaginal junction is recommended (grade IC). 2. The posterior peritoneum should be opened first (grade IC). 3. Clamping and cutting the uterosacral and cardinal ligaments before or after getting access into anterior peritoneum is recommended (grade IC). 4. Routine closure of the peritoneum during vaginal hysterectomy is not recommended (grade IB). 5. Vertical or horizontal closure of the vaginal vault following vaginal hysterectomy is recommended (grade IC). 6. To insert a vaginal plug following vaginal hysterectomy is not recommended (grade IB). CONCLUSION: Vaginal hysterectomy for a non-prolapsed uterus should be the preferential route for removing the uterus when hysterectomy is indicated. The ISGE provides evidence-based practical guidelines on how vaginal hysterectomy for non-prolapsed uterus should be undertaken. All efforts should be directed in teaching the surgical technique of vaginal hysterectomy during residency.

Hysteroscopic Diagnosis of Omentum Incarceration Subsequent to an Iatrogenic Uterine Perforation.

STUDY OBJECTIVE: To present and discuss the hysteroscopic aspects of incarcerated omentum through uterine perforation caused by previous dilation and curettage (D&C) for an incomplete first-trimester abortion. DESIGN: A case report. SETTING: Constantine University Hospital, Constantine, Algeria. PATIENT: A 40-year-old, gravida 3, para 2 patient, with a history of an incomplete first-trimester spontaneous abortion treated 6 months before by D&C requiring medical assistance because of moderate, chronic pelvic pain. No other clinical or biological alteration was found. The ultrasound showed intracavitary hyperechogenic formation infiltrating the myometrium posteriorly. INTERVENTIONS: Hysteroscopy revealed a fatlike lesion arousing suspicion of a residual trophoblast; the differential diagnosis included intramyometrial fat metaplasia as well [1]. A mechanical cold loop resection was initiated. Instrumental manipulation of the mass released yellow drops, probably of lipid nature, subsequently leading to the discovery of a uterine perforation giving passage to the omentum. Histologic examination confirmed fat tissue. There was immediate resolution of symptoms. Laparoscopic repair was subsequently performed and consisted of suturing the defect. There were no further complications. MEASUREMENTS AND MAIN RESULTS: Few cases of omentum incarceration in a perforated uterus diagnosed during laparotomy or by magnetic resonance imaging have previously been reported [2-4]. To our knowledge, this is the first case revealed through hysteroscopy. CONCLUSION: In women with a history of intracavitary interventions such as D&C, omentum incarceration should be considered when hysteroscopy demonstrates a fatlike formation and yellow droplets released by pressing or mobilizing the formation. Surgeons should be cautious, never using electrosurgery on formations whose origin arouses suspicion.

Evidence-based guidelines for vaginal hysterectomy of the International Society for Gynecologic Endoscopy (ISGE)

The ISGE Task Force for vaginal hysterectomy for non-prolapsed uterus defined key clinical questions that led the literature search and formulation of recommendations. The search included Medline/PubMed and Cochrane Database. English language articles were reviewed from January 2003 to January 2018, in conjunction with reviews published by the American College of Obstetricians and Gynecologists (ACOG) and the American Association of Gynecologic Laparoscopists (AAGL). The bibliographies of selected works were also checked to acquire additional data where relevant. The available information was graded by the level of evidence using the approach developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group. For each clinical question, the ISGE recommendations were defined in accordance with the evidence quality.

Evidence-based guidelines for vaginal hysterectomy of the International Society for Gynecologic Endoscopy (ISGE).

OBJECTIVE: This project was established by the International Society for Gynecologic Endoscopy (ISGE) to provide evidence-based recommendations on the selection of women in whom vaginal hysterectomy can be safely performed. STUDY DESIGN: The ISGE Task Force for vaginal hysterectomy for non-prolapsed uterus defined key clinical questions that led the literature search and formulation of recommendations. The search included Medline/PubMed and Cochrane Database. English language articles were reviewed from January 2003 to January 2018, in conjunction with reviews published by the American College of Obstetricians and Gynecologists (ACOG) and the American Association of Gynecologic Laparoscopists (AAGL). The bibliographies of selected works were also checked to acquire additional data where relevant. The available information was graded by the level of evidence using the approach developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group. For each clinical question, the ISGE recommendations were defined in accordance with the evidence quality. RESULTS: Six recommendations on patient selection for vaginal hysterectomy, including two grade 1B and four grade 2B recommendations were established. CONCLUSION: Vaginal hysterectomy for non-prolapsed uterus is the treatment of choice for many gynaecological patients in whom hysterectomy is indicated. It may be safely executed, and thus, should be offered to a large group of appropriately selected women, who today are operated in the main by the abdominal or laparoscopic approach. All efforts should be directed towards teaching the technique of vaginal hysterectomy during residency.

Assessing the risk of laparoscopic morcellation of occult uterine sarcomas during hysterectomy and myomectomy: Literature review and the ISGE recommendations.

OBJECTIVE: This project of the International Society for Gynecologic Endoscopy (ISGE) had the objective to review the literature and provide recommendations on the occult sarcoma risk assessment in patients who are candidates for minimally invasive gynecological surgery involving intra-abdominal electromechanical tissue morcellation. STUDY DESIGN: The ISGE Task Force for Estimation of the Risk in Endoscopic Morcellation initially defined key topics and clinical questions which may guide a comprehensive preoperative patient assessment. A literature search within the Medline/PubMed and Cochrane Database was carried out using keywords "morcellation", "uterine fibroids", "uterine sarcoma", "myomectomy" and "hysterectomy". Relevant publications (original studies, meta-analyses and previous reviews), written in English and published until May 30th, 2017, were selected and analyzed. Previously emitted statements of 12 recognized professional societies or government institutions and their supporting literature were also studied. For each topic/clinical question, the available information was graded by the level of evidence. The ISGE recommendations were established in accordance with the evidence quality. RESULTS: In the light of available information, 9 recommendations on preoperative clinical, laboratorial and imaging evaluation of the candidates for intracorporeal uterus/leiomyoma morcellation were formulated, mainly based on consensus and expert opinions. There is a lack of high-quality evidence, which does not allow the establishment of strong recommendations. CONCLUSION: Electromechanical tissue morcellation may be used in gynecological patients who are considered "low risk" upon appropriate preoperative evaluation; however, further studies and prospective data collection are greatly needed to improve sarcoma risk assessment in women with presumed uterine leiomyomas.

Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo.

BACKGROUND: The inhibition of Delta-like 4 (Dll4)/Notch signaling has been shown to result in excessive, nonfunctional vessel proliferation and significant tumor growth suppression. However, safety concerns emerged with the identification of side effects resulting from chronic Dll4/Notch blockade. Alternatively, we explored the endothelial Dll4 overexpression using different mouse tumor models. METHODS: We used a transgenic mouse model of endothelial-specific Dll4 overexpression, previously produced. Growth kinetics and vascular histopathology of several types of solid tumors was evaluated, namely Lewis Lung Carcinoma xenografts, chemically-induced skin papillomas and RIP1-Tag2 insulinomas. RESULTS: We found that increased Dll4/Notch signaling reduces tumor growth by reducing vascular endothelial growth factor (VEGF)-induced endothelial proliferation, tumor vessel density and overall tumor blood supply. In addition, Dll4 overexpression consistently improved tumor vascular maturation and functionality, as indicated by increased vessel calibers, enhanced mural cell recruitment and increased network perfusion. Importantly, the tumor vessel normalization is not more effective than restricted vessel proliferation, but was found to prevent metastasis formation and allow for increased delivery to the tumor of concomitant chemotherapy, improving its efficacy. CONCLUSIONS: By reducing endothelial sensitivity to VEGF, these results imply that Dll4/Notch stimulation in tumor microenvironment could be beneficial to solid cancer patient treatment by reducing primary tumor size, improving tumor drug delivery and reducing metastization. Endothelial specific Dll4 overexpression thus appears as a promising anti-angiogenic modality that might improve cancer control.

Incomplete Dll4/Notch signaling inhibition promotes functional angiogenesis supporting the growth of skin papillomas.

BACKGROUND: In invasive malignancies, Dll4/Notch signaling inhibition enhances non-functional vessel proliferation and limits tumor growth by reducing its blood perfusion. METHODS: To assess the effects of targeted Dll4 allelic deletion in the incipient stages of tumor pathogenesis, we chemically induced skin papillomas in wild-type and Dll4 (+/-) littermates, and compared tumor growth, their histological features, vascularization and the expression of angiogenesis-related molecules. RESULTS: We observed that Dll4 down-regulation promotes productive angiogenesis, although with less mature vessels, in chemically-induced pre-cancerous skin papillomas stimulating their growth. The increase in endothelial activation was associated with an increase in the VEGFR2 to VEGFR1 ratio, which neutralized the tumor-suppressive effect of VEGFR-targeting sorafenib. Thus, in early papillomas, lower levels of Dll4 increase vascularization through raised VEGFR2 levels, enhancing sensitivity to endogenous levels of VEGF, promoting functional angiogenesis and tumor growth. CONCLUSION: Tumor promoting effect of low-dosage inhibition needs to be considered when implementing Dll4 targeting therapies.

Spontaneous delivery through a cervical tear without cervical os dilatation.

Spontaneous delivery through a cervical tear, provoked by prostaglandin-induced uterine contractions, was described in a G2P0 woman with a history of cervical dilatation and uterine curettage. This rare complication with potentially serious maternal-fetal consequences can be predicted by an aberrant cervical response to prostaglandins in parturients with previous cervical interventions.

Developing a co-culture system for effective megakaryo/thrombopoiesis from umbilical cord blood hematopoietic stem/progenitor cells.

BACKGROUND AIMS: Platelet transfusion can be a life-saving procedure in different medical settings. Thus, there is an increasing demand for platelets, of which shelf-life is only 5 days. The efficient ex vivo biomanufacturing of platelets would allow overcoming the shortages of donated platelets. METHODS: We exploited a two-stage culture protocol aiming to study the effect of different parameters on the megakaryo/thrombopoiesis ex vivo. In the expansion stage, human umbilical cord blood (UCB)-derived CD34(+)-enriched cells were expanded in co-culture with human bone marrow mesenchymal stromal cells (BM-MSCs). The megakaryocytic commitment and platelet generation were studied, considering the impact of exogenous addition of thrombopoietin (TPO) in the expansion stage and a cytokine cocktail (Cyt) including TPO and interleukin-3 in the differentiation stage, with the use of different culture medium formulations, and in the presence/absence of BM-MSCs (direct versus non-direct cell-cell contact). RESULTS: Our results suggest that an early megakaryocytic commitment, driven by TPO addition during the expansion stage, further enhanced megakaryopoiesis. Importantly, the results suggest that co-culture with BM-MSCs under serum-free conditions combined with Cyt addition, in the differentiation stage, significantly improved the efficiency yield of megakaryo/thrombopoiesis as well as increasing %CD41, %CD42b and polyploid content; in particular, direct contact of expanded cells with BM-MSCs, in the differentiation stage, enhanced the efficiency yield of megakaryo/thrombopoiesis, despite inhibiting their maturation. CONCLUSIONS: The present study established an in vitro model for the hematopoietic niche that combines different biological factors, namely, the presence of stromal/accessory cells and biochemical cues, which mimics the BM niche and enhances an efficient megakaryo/thrombopoiesis process ex vivo.

Ultrasound antenatal detection of urinary tract anomalies in the last decade: outcome and prognosis.

OBJECTIVE: This study has been undertaken to determine the frequency and pattern of urinary tract anomalies diagnosed by ultrasound, to correlate the prenatal with postnatal diagnoses and to identify prognostic factors. METHODS: The Ultrasound Unit's database was reviewed for fetal urinary tract anomalies detected between January 2002 and June 2012. Prenatal diagnoses made by ultrasound were confirmed by postnatal ultrasound, as well as with surgical reports. Statistical analysis was performed using the Mann-Whitney U-test, Chi-square and Fisher's exact tests. p values <0.05 were considered significant. RESULTS: A total of 838 fetal malformations were prenatally diagnosed by ultrasound with a frequency of 21% of urinary tract anomalies (177/838). Renal pelvis dilatation and hydronephrosis accounted for more than half of the cases (52%). The most frequent postnatal diagnoses were also urinary tract dilatations. The prenatal diagnoses corresponded to the postnatal ones in 88.8% of cases. There was a highly significant association between anterior-posterior renal pelvis diameter above 10 mm in the last ultrasound performed before the birth and the need for surgery (p < 0.01). CONCLUSION: We emphasize the high degree of reliability of prenatal ultrasound in the establishment of diagnosis of urinary tract malformations and the prediction of postnatal outcomes.

Angiogenesis as a therapeutic target in endometriosis.

INTRODUCTION: Angiogenesis is a key factor for the successful establishment and growth of endometriotic lesions. MATERIAL AND METHODS: We performed a literature search in PubMed and reviewed the most pertinent studies published until January 2014 and focused on the endometriosis-associated angiogenesis and/or anti-angiogenic strategies for the treatment of this gynecological disorder. RESULTS: The present review provides a concise summary of the known molecular mechanisms that promote vascularization of endometriotic lesions and may serve as potential therapeutic targets. We also present a systematic overview of the inclusive and exclusive anti-angiogenic agents that have been already studied in cell cultures, animal models and/or endometriosis patients. DISCUSSION AND CONCLUSION: The integration of anti-angiogenic approaches in the multimodal management strategies for endometriosis patients will be conditioned by the outcomes of future assessments regarding the effectiveness of such treatments, the risk of drug resistance development and the incidence of unacceptable side effects.

Introdução: A angiogénese é um factor determinante no estabelecimento e desenvolvimento das lesões de endometriose. Material e Métodos: Foram revistos os artigos indexados na PubMed e incluídos os estudos mais relevantes, publicados até Janeiro de 2014, sobre a angiogénese nas lesões de endometriose e/ou estratégias anti-angiogénicas para o tratamento desta doença ginecológica. Resultados: O presente artigo fornece um resumo conciso dos mecanismos moleculares conhecidos que promovem a vascularização das lesões de endometriose, podendo servir como alvos terapêuticos potenciais. Apresenta-se também uma revisão sistemática dos agentes anti-angiogénicos, inclusivos e exclusivos, que já foram avaliados em culturas de células, modelos animais e/ou doentes com endometriose. Discussão e Conclusão: A integração das estratégias anti-angiogénicas na terapêutica multimodal de endometriose será condicionada pelos resultados de avaliações futuras da verdadeira eficácia desses tratamentos, do risco de desenvolvimento de resistência aos medicamentos e da incidência de efeitos colaterais inaceitáveis.