Margherita Dessole

Endometriosis in Adolescence

Endometriosis is a common cause of pelvic pain and infertility. The majority of women report symptoms since adolescence, and there are rare cases of endometriosis in premenarchal age patients. Symptoms in adolescence are similar to those in adulthood. Treatment usually consists of oral contraceptives and nonsteroidal anti-inflammatory drugs. In cases where this treatment is not successful, laparoscopy and biopsy of the lesions are necessary for diagnosis. However, emerging new technologies provide new options, in particular the use of serological markers.

Quality of Life in Women After Pelvic Exenteration for Gynecological Malignancies: A Multicentric Study.

Objectives This retrospective, multicentric study investigates quality-of-life issues and emotional distress in gynecological cancer survivors submitted to pelvic exenteration (PE). Methods The Global Health Status scale of European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30; the EORTC QLQ-CX24 (CX24), and EORTC QLQ-OV28 questionnaires were administered at least 12 months from surgery only in women with no evidence of further recurrence after PE. Statistical analysis was performed by the analysis of variance (for repeated measures. Results Ninety-six subjects affected by gynecological malignancies receiving PE were enrolled in the study. Anterior PE was performed in 47 patients (49%), posterior PE was performed in 29 cases (30.2%), and total PE performed in 20 women (20.8%). In 38 cases (39.6%), a definitive colostomy was performed. Urinary diversion with continent pouch was created in 11 patients. (11.5%), whereas in the remaining cases, a noncontinent pouch was reconstructed. Patients showed a significant discomfort in attitude to disease (71.5 ± 4.7), body image (48.9 ± 6.4), financial difficulties (56.2 ± 5.8), gastrointestinal symptoms (constipation, 47.8 ± 5.1; diarrhea, 62.4 ± 6.6; appetite loss, 43.6 ± 6.7), insomnia (64.5 ± 6.6), Global Health Status (64.6 ± 3.8), physical functioning (65.8 ± 4.6), role functioning (58.8 ± 5.8), and emotional functioning (67.4 ± 4.2). A higher number of ostomies (hazard rate [HR], 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of poorer Global Health Status scores. Older age (HR, 11.235; P = 0.003), vaginal/vulvar cancer (HR, 7.369; P = 0.013), total/posterior PE (HR, 7.393; P = 0.013), higher number of ostomies (HR, 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of lower body image levels. Conclusions Long-term psycho-oncological support is strongly recommended. The reduction of ostomies seems the most effective way to improve patients’ quality of life.

Efficacy and 9 years' follow-up of posterior intravaginal slingplasty for genital prolapse

The aim of this study was to assess the long‐term efficacy and complication rates of posterior intravaginal slingplasty (IVS) in women suffering from genital prolapse.

P16 immunostaining and HPV testing in histological specimens from the uterine cervix.

H rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and chronic obstructive pulmonary disease exacerbations. Currently there is no vaccine for RV which is most likely due to the existence of ~150 serotypes/strains and little or no cross-protective immunity generated from natural infections. Highly conserved regions of the RV polyprotein, when used as an immunogen, are hypothesized to generate broadly cross-reactive protective immunity to RV. A bioinformatic approach to define highly conserved areas of the RV proteome was performed. Recombinant protein was produced and tested for usefulness as candidate immunogen for a broadly cross-reactive vaccine using a mouse RV infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after challenge with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies, specific T cells and caused more rapid virus clearance. In conclusion, conserved domains of the RV capsid are immunogenic in mice, inducing cross-reactive immune responses that neutralize RV in vitro and are protective in vivo. This approach has identified a candidate for the continued development of a broadly reactive subunit RV vaccine.Background and Aim: High-risk type of human papilloma viruses (HPVs) can be considered as the etiologic agents of cervical cancer. At present, two prophylactic vaccines have been designed to prevent HPV infections. Both vaccines (Cervarix and Gardasil) are included VLP structure derived from L1 protein of HPV16 and 18. Both of these vaccines are highly immunogenic and elicit high titers of neutralizing antibody responses. Type-specific antibody responses of L1 VLPs are one limitation of these vaccines. So, current vaccine strategy provides protection against HPV types associated with cervical cancer and it won’t be able to induce immunity against other important HPV types. Alternatively, L2 minor capsid protein is a suitable candidate for next-generation of HPV vaccine. L2 has important functions in both papilloma virus assembly and the infectious process. Sequence analysis indicates L2 proteins as highly conserved with no changes in amino acid sequences during development. Indeed, L2 vaccine targeting can provide much more comprehensive protection against infection by various HPV types. However, L2 VLP typically elicits much lower neutralizing antibody titers than L1 VLP. The aim of this study is to evaluate the L1-L2 protein expression in mammalian cell lines.Objective: The presence of molds in a hospital environment became a subject of concern both for the healthcare professionals and for the users. Indeed, in spite of the absence of indicators allowing to measure their roles in the arisen of the fungal infections, it is established that bio contamination at the hospital is a major risk for the weakened patients, also for the certain places where are practiced the care or invasive acts. Their gravity is a real problem of Public health an in first row of morbidity, mortality. The causes are often multiple: air, water, renovation work without taking precautions standards, the cases of fungal contamination and the cases of fungal contamination we declared follow in serology realized.D decades of effort, an efficacious prophylactic HIV vaccine remains unavailable. To date, a number of pre-clinical and clinical studies have been conducted testing the efficacy of candidate HIV/SIV vaccines delivered by different viral vectors (e.g. Ad5, CMV and others. Despite inducing comparable levels of T cell responses, immunization with these candidate vaccines led to distinct outcomes of vaccine efficacy from stringent viral control to increased risk of HIV acquisition. The immunologic basis for such profound difference in vaccine effects on HIV acquisition is not known. CD4 T cells play a central role in orchestrating host immune responses by interacting with B cells, CD8 T cells and other innate immune effectors. However, CD4 T cells represent major target by HIV for infection and depletion in vivo. In our group, we have established a novel system assessing HIV infection of different antigen-specific CD4 T cells to HIV in vitro and found that human antigenspecific CD4 T cells manifest remarkable difference in susceptibility to HIV with CMV-specific CD4 T cells being particularly resistant compared to bacterial (tetanus toxoid) and fungal (Candida) antigens. More recently, we identified that human Ad5specific CD4 T cells are substantially more susceptible to HIV and are preferentially lost in HIV-infected individuals compared to CMV-specific CD4 T cells. Our findings suggest the importance of more thorough assessing the quality of vaccine-generated, vector and insert-specific CD4 T cells, and have important implications for testing new HIV/SIV vaccine antigens, vectors and adjuvants.Background: Since their discovery it has become clear that peroxisome proliferator-activated receptors (PPARs) are ligandactivated transcription factors involved in the genetic regulation of the lipid metabolism and energy homoeostasis. Subsequently, accumulating evidence suggests a role of PPARs in genomic pathways including the regulation of cell growth, apoptosis and differentiation. Recent studies point to the pathophysiological role of the peroxisome proliferators-activated receptor gamma (PPARgamma) in the inflammatory immune response. PPARs represent a major research target for the understanding and treatment of many skin diseases, such as benign epidermal tumors, psoriasis and atopic dermatitis.BACKGROUND The cellular tumor suppressor protein pl61NK4a (p16) has been identified as a biomarker for transforming human papilloma virus (HPV) infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell cycle and cell proliferation by inhibiting cell cycle G1 progression. PURPOSE OF THE STUDY To confirm the role of p16 as biomarker for transforming HPV infections and possible clinical applications in histological samples from the uterine cervix. MATERIALS AND METHODS The subject of this study included 56 biopsies of the cervical canal collected from January 2012 to September 2012 in the Institute of Pathology of the University of Sassari. The search for HPV immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while for the detection of p16 was used CINtecTM p16 (INK4a) histology kit. RESULTS In 56 biopsies performed in women aged between 23 and 69 years, the authors highlighted, by histological analysis, 24 cases of low-grade squamous intraepithelial lesion (LSIL) - cervical intraepithelial neoplasia (CIN1) and 31 cases of high-grade squamous intraepithelial lesion (HSIL) - CIN2/3); 15 CIN2, 14 CIN3, and two cervical squamous cell carcinoma in situ (SCIS). One case was an infiltrating squamous cell carcinoma (ISC). In 24 CIN1, there was a 16.67% positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2 the percentage of positivity for p16 was considerably increased (73.33%), unlike the search for HPV which had a positivity rate of 20%. Finally, in 14 cases of CIN3, and in three carcinomas, the positivity for p16 was equal to 100%, however the search for HPV positivity was between 0% and 7.14%. CONCLUSIONS These results demonstrated that p16 was a highly sensitive marker of cervical dysplasia. The authors have shown that p16 overexpression increased with the severity of cytological abnormalities and that had a greater ability to identify the viral infection compared to the classical immunohistochemical staining for HPV.W have used a number of techniques to identify tumour antigens recognized by the immune system of acute myeloid leukaemia (AML) patients including RT-PCR, SEREX, protein and cDNA arrays. We identified synovial sarcoma X breakpoint 2-interacting protein (SSX2IP) as a biomarker for survival. We analyzed 312 presentation AML samples and segregated AML patients based on aboveand below-median levels of expression of SSX2IP. Analysis of Kaplan-Meier curves showed a significant association between elevated SSX2IP expression and improved survival times in AML patients who lacked detectable cytogenetic abnormalities (log-rank test, n=180; P=0.007). We have also identified the cancer-testis antigen PASD1 through the immunoscreening of a testes cDNA library with pooled AML patient sera. We identified a number of algorithmselected naturally occurring 9 amino acid peptides which could bind HLA-A*0201 however these peptides failed to show detectable MHC binding in T2 assays. We modified one of the two anchor residues and showed these analogue peptides had enhanced binding, with decreased off-rates, in T2 assays. T cells from patients and normal donors responded to analogue peptide-loaded antigen presenting cells by secreting IFNγ. For clinical application, a DNA fusion gene vaccine encoding Pa14 was designed and tested in “humanized” mice. Splenocytes from vaccinated mice showed in vitro cytoxicity against tumor cells, either exogenously loaded with the corresponding wild type peptide (Pw8) or expressing endogenously processed PASD1 protein. We show for the first time that a DNA vaccine encoding an altered PASD1 epitope can induce CTL able to target the natural peptide expressed by human tumor cells.

Laparoscopic Neuronavigation for Deep Lateral Pelvic Endometriosis: Clinical and Surgical Implications

STUDY OBJECTIVE To evaluate the clinical presentation and surgical outcome in patients with deep lateral pelvic endometriosis (dLPE). DESIGN A retrospective multicentric study (Canadian Task Force classification II-2). SETTING University tertiary referral centers. PATIENTS One hundred forty-eight women with deep infiltrating endometriosis (DIE). INTERVENTIONS Laparoscopic excision of DIE. Disease distribution was classified as follows: central pelvic endometriosis (CPE) when DIE involved 1 of the following anatomic sites: cervix, vagina, uterosacral ligaments, rectum, bladder, or pelvic peritoneum; superficial lateral pelvic endometriosis when parametria, ureters, or hypogastric plexus were involved; and dLPE in the presence of sacral plexus and/or sciatic nerve infiltration. MEASUREMENTS AND MAIN RESULTS All patients showed CPE. LPE was detected in 116 cases (78.4%); among these, we observed dLPE in 41 patients (35.3%). dLPE occurred in 40% of women with CPE and in 72.7% of patients with hypogastric plexus involvement. Thirty women with dLPE (73.2%) received gastrointestinal or urologic resection in addition to gynecologic procedures compared with 40 patients (57.1%) without dLPE (p = .001). No differences were observed in terms of perioperative complications according to the presence of dLPE. According to univariate/multivariate analysis, chronic pelvic pain was the only predictor of dLPE (odds ratio = 3.041, p = .003). The median preoperative visual analog scale for dysmenorrhea (median = 8, range, 0-10) and dyspareunia (median = 5; range, 0-10) dropped to 0 after surgery. The median follow-up was 36 months (range, 6-66 months) with a recurrence rate of 8.8%. CONCLUSIONS dLPE is not a rare event in women with DIE. Complete laparoscopic removal of endometriosis seems to ensure benefit in terms of recurrence rate without increased surgical morbidities.

Peritoneal Sarcomatosis 5 Years after Laparoscopic Morcellation of Uterine Leiomyoma

FIGURE 3 Greater omentum Case notes In 2011, a 40-year-old woman underwent laparoscopic myomectomy with intraabdominal morcellation. Histology report showed leiomyoma without atypia, necrosis, or mitosis. In 2016, she complained of left lower quadrant pain; ultrasound examination revealed a left hypogastric mass in the site of trocar placement. Percutaneous biopsy results showed a low-grade endometrial stromal sarcoma (LGESS). At laparoscopy, we observed: multiple nodules on uterine serosa, left annex, vesical peritoneum (Figure 1), Douglas pouch (Supplementary Video 1), previous left pelvic trocar site (Figure 2), greater omentum (Figure 3), and right/left diaphragm.

Impact of first trimester fasting glycemic levels on expression of proteoglycans in pregnancy.

The aim of this study was to assess the influence of glucose metabolism on the expression of glycosaminoglycans (GAGs) and proteoglycans (PGs) in pregnant women.

Partial trisomy of the long arm of chromosome 1: Prenatal diagnosis, clinical evaluation and cytogenetic findings. Case report and review of the literature

Partial trisomy of the long arm of chromosome 1 is a relatively rare cytogenetic anomaly. Its phenotype has still not been completely defined, because of the cytogenetic heterogeneity of the cases so far described. We report a prenatal case of partial 1q trisomy associated with partial monosomy 4q, secondary to balanced maternal translocation t(1;4). The trisomic segment extended from 1q31.1 to qter and the monosomy 4q was from 4q35.2 to qter. The phenotypic anomalies found by post‐mortem and autopsy examinations were compared with those of similar cases reported in the literature. We performed standard cytogenetics and fluorescence in situ hybridization. Cerebral ventriculomegaly, present in our case, seemed to be a constant feature in partial 1q trisomies, so this cerebral malformation could be considered as the main echographic marker for this chromosomal imbalance and trisomy 1q should be added to the list of chromosomal abnormalities associated with ventriculomegaly.

Cesarean section: to be or not to be, is this the question?

Dear Editor,In the third millennium, there is a new ‘‘trend’’ of delivery:cesarean section (CS).Why the increasing rate? First of all, the delayedchildbearing, the second, safer anesthesia, and third, themedical litigation.The women, today, choose to get pregnant at an olderage in comparison to the XX century. What women want?Obviously, the women want one healthy newborn; thus,they do not accept to have a malformed fetus, an abortionor a complication through the vaginal delivery. However,medicine and obstetrics, in particular, are not exact sci-ences; in fact, complications (which may even be lethal)for the fetus and pregnant woman may occur, even in asmall percentage of cases, in spite of scrupulous manage-ment of pregnancy and labor.In Italy, about 38 % of women deliver by CS withhighest rate in the south of Italy (about 60 % in Campania).WHO in 1980 stated that 10 % of CS was the gold stan-dard, but now this rate is too low and is not achievable inthe third millennium.Recently, a Swedish study [1] demonstrated that twodecades after one birth, vaginal delivery was associatedwith a 67 % increased risk of urinary incontinence (UI),and UI[10 years increased by 275 % compared withcesarean section. Nowadays, an increasing number ofwomen request CS for non-medical indications, and forsome this demand appears to be motivated by a desire toprevent pelvic floor damage, including UI.A CS: is it always safe? Complications that are relatedto CS are increased risk of infections, transfusion, andprolonged hospitalization. CS gets maternal and fetalrisks. Maternal risk may be dangerous such as pulmonaryemboly. The fetal risks regard the procedure itself such as3.12 % accidental fetal lacerations per CS [2]. Recently,Arikan et al. [3] compared maternal and perinatal mor-tality and short-term outcomes of maternal and perinatalhealth between a CS group with relative indications and avaginal delivery group. Maternal morbidity was signifi-cantly lower in the vaginal birth group than the CS group(7 vs 30, p\0.05). Perinatal mortality and perinatalmorbidity were not significantly different between the twogroups. Newborns with the first minute Apgar scorebelow 7 were higher in the CS group (p\0.05). The fifthminute Apgar scores and umbilical cord pH values weresimilar. The authors concluded that short-term maternalcomplications were more frequently seen in cesareandeliveries with relative indications than spontaneousvaginal deliveries. Furthermore, a recent cochrane data-base systematic review [4] assessed the effects of a policyof planned immediate cesarean delivery versus plannedvaginal birth for women in preterm labour and concludedthat there is not enough evidence to evaluate the use of apolicy of planned immediate cesarean delivery for pre-term babies.The last but not the least: medical litigation is increasingin all the world. In some countries, no medical doctor wantto be obstetrician for the fear of medical litigation andbecause the medical insurance do not cover the obstetri-cian, especially if the obstetrician had a previous compli-cation during delivery and relative compliant.

Self-Reported Long-Term Autonomic Function After Laparoscopic Total Mesometrial Resection for Early-Stage Cervical Cancer: A Multicentric Study

Objectives This multicentric retrospective study investigates the early and long-term self-reported urinary, bowel, and sexual dysfunctions in early-stage cervical cancer patients who submitted to laparoscopic total mesometrial resection (L-TMMR), total laparoscopic radical hysterectomy, vaginal-assisted laparoscopic radical hysterectomy, and laparoscopic-assisted radical vaginal hysterectomy. Methods Cervical cancer patients, FIGO (International Federation of Gynecology and Obstetrics) stage IA2–IB1/IIA1 who submitted to nerve-sparing radical hysterectomy were recruited. Pelvic functions were assessed within 30 days (early outcome) and 12 months after surgery (long-term outcome). Results Two hundred thirteen subjects receiving nerve-sparing radical hysterectomy were enrolled. Laparoscopic total mesometrial resection was performed in 46 patients (21.6%), total laparoscopic radical hysterectomy in 65 patients (30.5%), vaginal-assisted laparoscopic radical hysterectomy in 54 patients (25.4%), and laparoscopic-assisted radical vaginal hysterectomy in 48 women (22.5%). Operative time was significantly lower in the L-TMMR group (240 minutes; range, 120–670 minutes; P = 0.001). The overall perioperative complication rate was 11.3%, with no statistically significant differences among the 4 groups. Stress incontinence and sensation of bladder incomplete emptying were detected, respectively, in 54 patients (25.6%) and 65 patients (30.7%) with a significantly lower prevalence among those in the L-TMMR group, which resulted, respectively, in 11.1% (P = 0.022) and 13.3% (P = 0.036). The prevalence rates of constipation, sensation of incomplete bowel emptying, and effort during evacuation were significantly higher among those in the L-TMMR group, resulting in, respectively, 37% (P = 0.001), 42.3% (P = 0.012), and 50% (P = 0.039). One hundred forty-nine patients (70%) were sexually active. Fifty-eight women (38.9%) reported low enjoyment, 83 women (55.7%) medium enjoyment, and 8 women (5.4%) reported high enjoyment, without statistically significant differences among the 4 groups. Conclusions Laparoscopic total mesometrial resection is associated with improved long-term urinary autonomic functions and worse gastrointestinal autonomic outcome. Further larger prospective trials are needed to evaluate both the oncological and functional outcomes in order to establish the most appropriate surgical approach for early-stage cervical cancer patients.