Non-invasive prenatal test identifies circulating cell-free DNA chromosomal abnormalities derived from clonal hematopoiesis in aggressive hematological malignancies.

Liquid biopsy is a minimally invasive diagnostic tool for identification of tumor-related mutations in circulating cell-free DNA (cfDNA). The aim of this study was to investigate feasibility, sensitivity, and specificity of non-invasive prenatal test (NIPT) for identification of chromosomal abnormalities in cfDNA from a total of 77 consecutive patients with non-Hodgkin B-cell lymphomas, Hodgkin lymphoma (HL), or plasma cell dyscrasia. In this case series, half of patients had at least one alteration, more frequently in chromosome 6 (23.1%), chromosome 9 (20.5%), and chromosomes 3 and 18 (16.7%), with losses of chromosome 6 and gains of chromosome 7 negatively impacting on overall survival (OS), with a 5-year OS of 26.9% and a median OS of 14.6 months, respectively (P = 0.0009 and P = 0.0004). Moreover, B-cell lymphomas had the highest NIPT positivity, especially those with aggressive lymphomas, while patients with plasma cell dyscrasia with extramedullary disease had a higher NIPT positivity compared to conventional cytogenetics analysis and a worse outcome. Therefore, we proposed a NIPT-based liquid biopsy a complementary minimally invasive tool for chromosomal abnormality detection in hematological malignancies. However, prospective studies on larger cohorts are needed to validate clinical utility of NIPT-based liquid biopsy in routinely clinical practice.

Mesenchymal Stem Cells from the Wharton's Jelly of the Human Umbilical Cord: Biological Properties and Therapeutic Potential.

Wharton's jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiative potential, an immuno-privileged status and easy access for collection, which raise no legal or ethical issues. WJ-MSCs exhibit several features of embryonic stem cells, both in the phenotypic and genetic aspects, with only a few differences, such as a shorter doubling time and a more extensive ex vivo expansion capacity. WJ-MSCs have immunomodulatory properties, involving both innate and adaptive immune responses. This review focuses on the role of WJ-MSCs in the management of graft-versus-host disease (GvHD), a life-threatening complication of the allogenic transplantation of hematopoietic stem cells. Different studies documented the beneficial effect of the infusion of WJ-MSCs, even when not fully HLA identical, in patients with severe GvHD, refractory to standard treatment. Finally, we summarized current ongoing clinical trials with WJ-MSCs and their potential in regenerative medicine.

Identification of long non­coding RNA expression patterns useful for molecular­based classification of type I endometrial cancers.

Endometrial cancer is the most frequently diagnosed gynecologic malignant disease. Although several genetic alterations have been associated with the increased risk of endometrial cancer, to date, the diagnosis and prognosis still rely on morphological features of the tumor, such as histological type, grading and invasiveness. As molecular­based classification is desirable for optimal treatment and prognosis of these cancers, we explored the potential of lncRNAs as molecular biomarkers. To this end, we first identified by RNA sequencing (RNA­Seq) a set of lncRNAs differentially expressed in cancer vs. normal endometrial tissues, a result confirmed also by analysis of normal and cancerous endometrium RNA­Seq data from TCGA (The Cancer Genome Atlas). A significant association of a subset of these differentially expressed lncRNAs with tumor grade was then determined in 405 TCGA endometrial cancer profiles. Integrating endometrial cancer­specific expression profiles of long and small non­coding RNAs, a functional association network was then identified. These results describe for the first time a functional ῾coreá¾½ network, comprising small and long RNAs, whose deregulation is associated with endometrial neoplastic transformation, representing a set of cancer biomarkers that can be monitored and targeted for diagnosis, follow­up and therapy of these tumors.

Reproductive issues in patients undergoing Hematopoietic Stem Cell Transplantation: an update.

In 1963 George Mathé announced to the world that he had cured a patient of leukaemia by means of a bone-marrow transplant. Since than much progress has been made and nowadays Hematopoietic Stem Cell Transplantation (HSCT) is considered the most effective treatment of numerous severe haematological diseases. Gynaecological complications in HSCT women represent a serious concern for these patients, but often underestimated by clinicians in the view of Overall Survival. The main gynaecological complications of HSCT are represented by: premature ovarian failure (POF), thrombocytopenia-associated menorrhagia, genital symptoms or sexual problems in course of chronic GVHD (cGVHD), osteoporosis, secondary solid tumours due to immunosuppressive drugs to treat cGVHD and severity of cGVHD, and fertility and pregnancy issues. In particular fertility-related issues are always more relevant for patients, whose life expectation is constantly growing up after HSCT.Thus, taking care of a patient undergoing HSCT should primarily include gynaecological evaluation, even before conditioning regimen or chemotherapy for the underlying malignancy, as, in our opinion, it is of great importance to ensure a complete diagnostic work-up and intervention options to guarantee maximum reproductive health and a better quality of life in HSCT women.The present review aims at describing principal features of the aforementioned gynaecological complications of HSCT, and to define, on the basis of current international literature, a specific protocol for the prevention, diagnosis, management and follow-up of gynaecological complications of both autologous and heterologous transplantation, before and after the procedure.

Thalassemia and infertility.

Beta-thalassemia (BTM) major is the most common haemoglobin disorder in the world, with high prevalence in people of Mediterranean, Arab or Asian origin. It has been estimated that about 1.5% of the global population (80-90 million people) are carriers of BTM. In patients with BTM, long-term transfusion therapy for the correction of anaemia leads to toxic iron overload, resulting in significant morbidity including liver damage, cardiac complications and endocrine dysfunction. The commonest abnormality is hypogonadotropic hypogonadism, which presents with primary amenorrhoea, delayed puberty or secondary amenorrhoea with consequent infertility. Nevertheless, current improvements in the management of thalassemia disorders offer patients the possibility of having a regularly functioning reproductive system and increased chances of achieving a pregnancy. The aim of the present review is to analyse all aspects of fertility management in BTM women, by examining the main causes of infertility, in order to give practical tools to ensure a complete diagnostic work-up and discuss intervention options to guarantee maximum reproductive health.

Triclosan and bisphenol a affect decidualization of human endometrial stromal cells.

In recent years, impaired fertility and endometrium related diseases are increased. Many evidences suggest that environmental pollution might be considered a risk factor for endometrial physiopathology. Among environmental pollutants, endocrine disrupting chemicals (EDCs) act on endocrine system, causing hormonal imbalance which, in turn, leads to female and male reproductive dysfunctions. In this work, we studied the effects of triclosan (TCL) and bisphenol A (BPA), two widespread EDCs, on human endometrial stromal cells (ESCs), derived from endometrial biopsies from woman not affected by endometriosis. Cell proliferation, cell cycle, migration and decidualization mechanisms were investigated. Treatments have been performed with both the EDCs separately or in presence and in absence of progesterone used as decidualization stimulus. Both TCL and BPA did not affect cell proliferation, but they arrested ESCs at G2/M phase of cell cycle enhancing cell migration. TCL and BPA also increased gene expression and protein levels of some decidualization markers, such as insulin growth factor binding protein 1 (IGFBP1) and prolactin (PRL), amplifying the effect of progesterone alone. All together, our data strongly suggest that TCL and BPA might alter human endometrium physiology so affecting fertility and pregnancy outcome.

Exposure to di-2-ethylhexyl phthalate, di-n-butyl phthalate and bisphenol A through infant formulas.

Phthalates and bisphenol A (BPA) are ubiquitous contaminants identified as endocrine disruptors. Phthalates are worldwide used as plasticizers, in particular to improve the mechanical properties of polymers such as polyvinyl chloride. Because they are not chemically bound to the polymer, they tend to leach out with time and use. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP) are the two most common phthalates. BPA is an estrogenic compound used to manufacture polycarbonate containers for food and drink, including baby bottles. It can migrate from container into foods, especially at elevated temperatures. Diet is a predominant source of exposure for phthalates and BPA, especially for infants. The aim of this study was to test the presence of DEHP, DnBP, and BPA in infant formulas. DEHP, DnBP, and BPA concentrations were measured in 22 liquid and 28 powder milks by gas chromatography with flame ionization detection and high performance liquid chromatography with fluorimetric detection, respectively. DEHP concentrations in our samples were between 0.005 and 5.088 µg/g (median 0.906 µg/g), DnBP concentrations were between 0.008 and 1.297 µg/g (median 0.053 µg/g), and BPA concentrations were between 0.003 and 0.375 µg/g (median 0.015 µg/g). Concentrations of the investigated contaminants in liquid and powder milks were not significantly different, even though samples were packed in different types of containers. These data point out potential hazards for infants fed with baby formulas. Contamination seems more related to the production of formulas than to a release from containers.

Is it possible to predict office hysteroscopy failure?

OBJECTIVE: The purpose of this study was to develop a clinical tool, the HFI (Hysteroscopy Failure Index), which gives criteria to predict hysteroscopic examination failure. STUDY DESIGN: This was a retrospective diagnostic test study, aimed to validate the HFI, set at the Department of Gynaecology, Obstetric and Reproductive Science of the Second University of Naples, Italy. The HFI was applied to our database of 995 consecutive women, who underwent office based to assess abnormal uterine bleeding (AUB), infertility, cervical polyps, and abnormal sonographic patterns (postmenopausal endometrial thickness of more than 5mm, endometrial hyperechogenic spots, irregular endometrial line, suspect of uterine septa). Demographic characteristics, previous surgery, recurrent infections, sonographic data, Estro-Progestins, IUD and menopausal status were collected. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of the model to identify patients who were correctly identified (true positives) divided by the total number of failed hysteroscopies (true positives+false negatives). Positive and Negative Likelihood Ratios with 95%CI were calculated. RESULTS: The HFI score is able to predict office hysteroscopy failure in 76% of cases. Moreover, the Positive likelihood ratio was 11.37 (95% CI: 8.49-15.21), and the Negative likelihood ratio was 0.33 (95% CI: 0.27-0.41). CONCLUSION: Hysteroscopy failure index was able to retrospectively predict office hysteroscopy failure.

Biomechanical features of bidirectional-barbed suture: a randomized laboratory analysis.

The aim of the current prospective study was to evaluate the biomechanical stability of barbed suture vs. conventional suture. Biomechanical stability of a 14x14-cm PDO/polydioxanone, with a half circle and 36-mm needle, bidirectional barbed 0-Quill suture (Angiotech, Vancouver, British Columbia, Canada) vs. 1-Poliglecaprone 25 (Monocryl, Ethicon, Inc, Somerville, NJ) suture was evaluated on biological specimens. The 1-Monocryl suture was chosen because it is widely used by gynecological surgeons in the repair either of the vaginal cuff or the uterine wall defects. Forty specimens of aponeurotic muscle, obtained from abdominal wall of a lamb, were prepared, and randomly assigned to 1 of 2 repair groups: Group A (n = 20) classic repair with 1-Monocryl suture; Group B (n = 20) 0-Quill barbed suture. Each specimen was transected at the midpoint and then repaired. Biomechanical stability of the repaired specimen was verified on a CMT6000 electromechanical universal testing machine (SANS, MTS SYSTEMS, China Co., Ltd., Shenzhen, China), with a 1kN cell. Biomechanical tests showed that maximum force was similar for 1-Monocryl and 0-Quill respectively (p = non-significant). This randomized laboratory study shows that biomechanical stability of the sutures is comparable.

Bidirectional barbed suture in laparoscopic myomectomy: clinical features.

OBJECTIVE: To compare bidirectional knotless barbed suture versus standard sutures, with either extracorporeal or intracorporeal knots, and to assess the feasibility, safety, and rapidity in repairing a uterine wall defect after laparoscopic myomectomy. SUBJECTS AND METHODS: This was a randomized clinical study having a Canadian Task Force Classification of I. In tertiary-care university-based teaching hospitals, 117 women who underwent laparoscopic myomectomy were enrolled. In accord with randomization, uterine wall defects were closed with either extracorporeal (poliglecaprone 25; Monocryl™-1; Ethicon Inc., Somerville, NJ) or intracorporeal (polyglactin 910; Vicryl™-1; Ethicon Inc.) knots or a bidirectional knotless barbed suture (Quill™-0; Angiotech Pharmaceuticals, Inc., Vancouver, BC, Canada). RESULTS: Time required to suture was significantly lower in the group operated on with a bidirectional suture than in groups with traditional sutures (P<.001). No significant difference was observed in operative time among the study groups. The degree of surgical difficulty was significantly lower in the Quill group than in the other groups. CONCLUSIONS: Use of barbed sutures reduces the time required to repair a uterine wall defect during laparoscopic myomectomy. In a follow-up of patients carried out at 3 months, 6 months, and 1 year after the surgery, there were no wound dehiscence, no bleeding, and no other potential major complications.

Minilaparoscopic myomectomy: a mini-invasive technical variant.

OBJECTIVE: We propose a mini-invasive technical variant for laparoscopic myomectomy, which is currently less invasive and more feasible. STUDY DESIGN: This was a prospective, controlled, randomized trial, involving 170 patients, who underwent laparoscopic myomectomy. Patients were randomized into two groups: Group A (n=98) underwent standard laparoscopic myomectomy, and Group B (n=72) underwent the mini-invasive technique. The current mini-invasive variant is performed with a 10-mm umbilical trocar and only two 5-mm ancillary trocars. Morcellation is transumbilical: a 0° 5-mm optical system is used and is inserted either in the left or in the right iliac trocar according to the surgeon's preference. RESULTS: The degree of surgical difficulty, evaluated using a visual analog scale (VAS), was similar in the two groups (P=nonsignificant). Postoperative pain measured on a VAS scale showed there was less pain experienced in patients in Group B than in Group A (P<.01). Esthetic results measured on a VAS scale showed a higher compliance for patients in Group B than Group A (P<.01). CONCLUSIONS: The mini-invasive laparoscopic myomectomy described is, in our opinion, currently less invasive and more feasible than techniques usually used. Finally, this technique is a valid approach for the surgeon, and it gives women very acceptable aesthetic results.

Bidirectional barbed suture in total laparoscopic hysterectomy and lymph node dissection for endometrial cancer: technical evaluation and 1-year follow-up of 61 patients.

OBJECTIVE: This randomized clinical study compared the feasibility and safety of the shortest suture for bidirectional knotless barbed versus standard sutures, with either extracorporeal or intracorporeal knots, for vaginal cuff closure following total laparoscopic hysterectomy (TLH) and lymph node dissection for early endometrial cancer. SUBJECTS AND METHODS: The study design was Canadian Task Force Classification I. In tertiary-care university-based teaching hospitals, 61 women underwent TLH and lymph node dissection. In accord with randomization, the vaginal cuff in TLH was closed with either extracorporeal or intracorporeal knots (1-Monocryl(®); Ethicon Inc., Somerville, NJ) and a bidirectional knotless barbed suture (0-Quill™; Angiotech Pharmaceuticals, Inc., Vancouver, BC, Canada). All patients were evaluated at 3-month, 6-month, and 1-year follow-up. RESULTS: Time required to suture was significantly lower in the group treated with bidirectional suture than in groups with traditional sutures (P<.001). No significant difference was observed in the operative time between the study groups. The degree of surgical difficulty was significantly lower in the bidirectional barbed suture group than in the other groups. At 1-year follow-up all patients presented no wound dehiscence, no bleeding, dyspareunia, and other potential major complications such as ureteric, bladder, or bowel injury. CONCLUSIONS: Use of a barbed suture reduces the time required to repair the vaginal cuff during TLH. At follow-up of patients, carried out 3 months, 6 months, and 1 year after the surgery, no wound dehiscence, no bleeding, or no other potential major surgical complications had occurred.

Selective salpingography: preliminary experience of an office operative option for proximal tubal recanalization.

OBJECTIVE: To evaluate treatment efficacy and patient acceptability of the new Radiographic Tubal Assessment Set (RTAS) (Cook Ireland Ltd., Limerick, Ireland) for selective salpingography (SSG). STUDY DESIGN: 33 women, between 23 and 38 years old, referred to the Fertility Centre of the Department of Obstetrics, Gynecology and Reproductive Science, Second University of Naples, for sterility problems, underwent an office operative SSG with the RTAS. Of the 33 women, 12 had bilateral tubal obstruction (Group A) and 21 had unilateral tubal obstruction (Group B). Patients who did not regain tubal patency were referred for laparoscopic surgery. To verify patient acceptability, a visual analogue score (VAS 1-10) of pain was completed immediately after the procedure. RESULTS: From a total of 45 obstructed fallopian tubes, 34 were recanalized, giving a success rate for the procedure of 75.6% (p<0.001). Nine patients with bilateral tubal obstruction (Group A) had the tubes recanalized and five obtained a spontaneous pregnancy. Sixteen patients with monolateral tubal obstruction (Group B) had the tubes recanalized and nine obtained a spontaneous pregnancy. A total of seven patients were sent for operative laparoscopy: four of them had the tubes recanalized and two obtained a spontaneous pregnancy. One patient was lost to follow-up. The evaluation of the level of pain felt during the procedure on the 10 cm VAS showed mean pelvic pain 2.9 ± 2.2, and an incidence of no discomfort±low pain significantly higher than moderate±severe pain (p<0.0001). CONCLUSION: The RTAS can be considered a safe and effective tool to perform this office operative procedure for tubal recanalization, with a high acceptability for the patient. The "see and treat" approach in patients with proximal tubal obstruction (PTO) suggests for the future the use of this device under sonographic guidance, taking into account accurate patient selection.

Laparoscopic myomectomy of a subserous pedunculated fibroid at 14 weeks of pregnancy: a case report.

INTRODUCTION: Uterine leiomyomas are seen in 1.6% to 4% of pregnancies. With the increasing age of obstetric patients, more cases are being encountered during pregnancy. CASE PRESENTATION: We report the case of a 31-year-old Caucasian woman with acute recurrent abdominal pain due to a subserous fundic myoma, measuring 48 × 52 × 63 mm, with an implantation base of 22 × 18 mm, which was successfully treated by laparoscopy at 14 weeks of pregnancy. At a gestational age of week 40, the patient spontaneously delivered a healthy 3216 g girl baby. CONCLUSION: As far as we know, this is the first reported case of laparoscopic myomectomy this early during a pregnancy. Our experience together with an analysis of cases reported in the literature suggests that myomectomy during pregnancy may be considered safe, but only in the hands of experienced laparoscopic surgeons. There are a few reports in the literature about laparoscopic myomectomy during the first half of pregnancy that demonstrate its feasibility in selected cases. Some technical tools could improve the procedure with a minimum of risk for the ongoing pregnancy.

Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study.

OBJECTIVE: Aim of our study was to evaluate the effectiveness of the association between N-Palmitoylethanolamine and transpolydatin in the management of chronic pelvic pain related to EMS. STUDY DESIGN: This was a randomized, double-blind, parallel-group, placebo-controlled clinical trial involving 61 subjects, submitted to a first line laparoscopic conservative surgery, who were randomized into 3 groups receiving: group A (n=21) the association N-Palmitoylethanolamine-transpolydatin 400 mg + 40 mg twice a day for 3 months; group B (n=20) the placebo for 3 months; group C (n=20) a single course of Celecoxib 200mg twice a day for 7 consecutive days. Assessments of the severity of pelvic endometriosis (pelvic pain, dysmenorrhoea and dyspareunia) were recorded before and after treatment on a questionnaire and a 10-point VAS. Differences between groups were verified with Kruskal-Wallis ANOVA for non-parametric multiple comparisons. RESULTS: A marked decrease in dysmenorrhoea, dyspareunia and pelvic pain was observed in all groups, and the association between N-Palmitoylethanolamine and transpolydatin resulted to be more effective than placebo (P<.001). Additionally, the treatment with Celecoxib resulted in a decrease in pelvic pain more effective either than the association N-Palmitoylethanolamine and transpolydatin or placebo. CONCLUSION: These preliminary results show that the association between micronized N-Palmitoylethanolamine and transpolydatin is effective in the management of pelvic pain related to endometriosis after laparoscopy. Additionally, this association seems to be safe, shows an optimal control of pain and can be used in patients who are unable to receive other therapies.

Are diabetes, hypertension, and obesity independent risk factors for endometrial polyps?

STUDY OBJECTIVE: To investigate whether diabetes, hypertension (HTN), and obesity can be considered risk factors for endometrial polyps (EPs) independently of age and menopausal status. DESIGN: Retrospective analysis (Canadian Task Force classification III). SETTING: Department of Obstetrics and Gynecology of the University of Foggia, Italy. PATIENTS: A total of 353 Caucasian women undergoing office hysteroscopy to assess abnormal uterine bleeding, infertility, cervical polyps, and abnormal sonographic patterns. INTERVENTIONS: Demographic characteristics and data on diabetes, HTN, and menopausal status were collected and anthropometric parameters were analyzed. Vaginoscopic hysteroscopy was performed with a 5-mm continuous-flow operative office hysteroscope. When present, EPs were treated during the same procedure by means of 5-Fr scissors or electrode. MEASUREMENTS AND MAIN RESULTS: In 134 (38%) of 353 cases, EPs were found. Univariable and multivariable analysis were performed to verify the presence of a statistically significant association among age, menopause, HTN, obesity, diabetes (independent variables), and the presence of EPs. Univariable logistic analysis showed a statistically significant association among age, menopause, HTN, obesity, and the presence of EPs. However, when multivariable logistic regression was performed, all the independent variables, except age, lost statistical significance (OR 1.05, 95% CI 1.02-1.07, p <.001). CONCLUSION: Although it appears that EP is a disorder of aging, the significance of diabetes, HTN, and obesity, as well as menopause, on the development of EPs should be reconsidered.

Hysteroscopic removal of gauze packing inadvertently sutured to the uterine cavity: report of 2 cases.

We report on 2 cases of successful hysteroscopic removal of uterovaginal packing, inserted during cesarean sections after uterine hemorrhage resistant to medical therapy. The packing, in both cases, could not be removed vaginally with sponge forceps because the packing had been sutured to the uterine cavity. A hysteroscopic approach enabled identification and cutting with 5F scissors of the stitches fixing the packing to the uterine walls, allowing straightforward removal in an outpatient setting and avoiding a repeated laparotomy. Some useful techniques to handle such a situation are described.