Gynaecol og y. Italian Journal of. The Official Journal of the Società Italiana di Ginecologia e Ostetricia (SIGO) Partner-Graf.

Dimensione: px
Iniziare la visualizzazioe della pagina:

Download "Gynaecol og y. Italian Journal of. The Official Journal of the Società Italiana di Ginecologia e Ostetricia (SIGO) Partner-Graf."

Transcript

1 Italian Journal of Gynaecol og y & Obstetrics The Official Journal of the Società Italiana di Ginecologia e Ostetricia (SIGO) March Vol N. 1 - Quarterly - ISSN Quarterly Partner-Graf 1

2

3 Italian Journal of Gynae col og y & Obstetrics The Official Journal of the Società Italiana di Ginecologia e Ostetricia (SIGO) Quarterly Partner-Graf

4 Editor in Chief Paolo Scollo, Catania Editors Herbert Valensise, Roma Enrico Vizza, Roma Editoral Board Cervigni Mauro, Roma Chiantera Vito, Napoli Costa Mauro, Genova De Stefano Cristofaro, Avellino De Vita Davide, Salerno La Sala Giovanni Battista, Reggio Emilia Locci Maria Vittoria, Napoli Marci Roberto, Roma Monni Giovanni, Cagliari Ragusa Antonio Franco, Milano Sirimarco Fabio, Napoli Trojano Vito, Bari Viora Elsa, Torino Editoral Staff Roberto Zerbinati Serena Zerbinati Management, Administrative office Partner-Graf Srl - Via F. Ferrucci, Prato Tel Fax The Italian Journal of Gynaecology & Obstetrics is a digital magazine. You can download it freely from or

5 It. J. Gynaecol. Obstet. 2014, 26: N.4 Table of contents Editorial. The two genes and the Jolie s Sindrome Paolo Scollo Laparoscopic radical hysterectomy with the use of SNAIL Tenaculum. A simplified uterine manipulator for the management of early cervical cancer Francesco Barletta, Giacomo Corrado, Enrico Vizza 6 9 Vaginal Erbium Laser: the Second Generation Thermotherapy for the Genitourinary Syndrome of Menopause (GSM) in Breast Cancer Survivors. A preliminary report of a pilot study Marco Gambacciani, Marco Levancini New therapeutic strategies in short cervical length: Arabin pessaries Lucio Juliano, Fabiana De Benedictis, Teresa Guarino, Maria Giovanna Schiattarella Studio Aldati Napoli Serum C-reactive protein as potential independent prognostic factor for breast cancer Adela Stoenescu, Christoph Gerlinger, Erich Franz Solomayer, Christoph Scholz, Ingolf Juhasz- Böss, Julia Radosa

6 It. J. Gynaecol. Obstet. 2015, 27: N.1 Editorial The two genes and the "Jolie's Sindrome" Paolo Scollo The recent decision of Angeline Jolie to undergo to a prophylactic BSO and, the following worldwide media debate focused again the attention of millions of women on this topic. Not always in the right way. BRCA1 and BRCA2 are human genes that produce tumour suppressor proteins. These proteins help repair damaged DNA and, therefore, play a role in ensuring the stability of the cell s genetic material. When either of these genes is mutated, or altered, such that its protein product is not made or does not function correctly, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer. A harmful BRCA1 or BRCA2 mutation can be inherited from a person s mother or father. Each child of a parent who carries a mutation in one of these genes has a 50 percent chance of inheriting the mutation. The effects of mutations in BRCA1 and BRCA2 are seen even when a person s second copy of the gene is normal. Specific inherited mutations in BRCA1 and BRCA2 increase the risk of female breast and ovarian cancers, and they have been associated with increased risks of several additional types of cancer. Together, BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers and about 5 to 10 percent of all breast cancers. In addition, mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers overall. Breast cancers associated with BRCA1 and BRCA2 mutations tend to develop at younger ages than sporadic breast cancers. Moreover, harmful mutations in BRCA1 and BRCA2 increase the risk of several cancers in addition to breast and ovarian cancer. BRCA1 mutations may increase a woman s risk of developing fallopian tube cancer and peritoneal cancer. Men with BRCA2 mutations, and to a lesser extent BRCA1 mutations, are also at increased risk of breast cancer. Men with harmful BRCA1 or BRCA2 mutations have a higher risk of prostate cancer. Men and women with BRCA1 or BRCA2 mutations may be at increased risk of pancreatic cancer. Several options are available for managing cancer risk in individuals who have a known harmful BRCA1 or BRCA2 mutation. These include enhanced screening, prophylactic (risk-reducing) and surgery. Enhanced Screening. Some women who test positive for BRCA1 and BRCA2 mutations may choose to start screening at younger ages than the general population or have more frequent screening. For example, some experts recommend that women who carry a harmful BRCA1 or BRCA2 mutation undergo clinical breast examinations beginning at age 25 to 35 years. And some expert groups recommend that women who carry such a mutation have a mammogram every year, beginning at age 25 to 35 years. Unfortunately, no effective methods of ovarian cancer screening currently exist. Some groups recommend transvaginal ultrasound examinations, blood tests for the antigen CA-125, and clinical examinations for ovarian cancer screening in women with harmful BRCA1 or BRCA2 mutations, but none of these methods appears to detect ovarian tumours at an early enough stage to reduce the risk of dying from ovarian cancer. The benefits of screening for breast and other cancers in men who carry harmful mutations in BRCA1 or BRCA2 is also not known, but some expert groups recommend that men who are known to carry a harmful mutation undergo regular mammography as well as testing for prostate cancer. 6 Prophylactic (Risk-reducing) Surgery. Prophylactic surgery involves removing as much of the "at-risk" tissue as possible. Women may choose to have both breasts removed (bilateral prophylactic mastectomy) to reduce their risk of breast cancer. Surgery to remove a woman's ovaries and fallopian tubes (bilateral prophylactic salpingo-oophorectomy) can help reduce her risk of ovarian cancer. Removing the ovaries also reduces the risk of breast cancer in premenopausal women by eliminating a source of hormones that can fuel the growth of some types of breast cancer. Prophylactic surgery does not completely guarantee that cancer will not develop because not all at-risk tissue can be removed by these procedures. Some women have developed breast cancer, ovarian cancer, or primary peritoneal carcinomatosis (a type of cancer similar to ovarian cancer) even after prophylactic surgery. Nevertheless,

7 Editorial the mortality reduction associated with this surgery is substantial: one study showed that women who underwent bilateral prophylactic salpingo-oophorectomy had a nearly 80 percent reduction in risk of dying from ovarian cancer and a more than 50 percent reduction in risk of dying from breast cancer. No evidence is available regarding the effectiveness of bilateral prophylactic mastectomy in reducing breast cancer risk in men with a harmful BRCA1 or BRCA2 mutation or a family history of breast cancer. Therefore, bilateral prophylactic mastectomy for men at high risk of breast cancer is considered an experimental procedure, and insurance companies will not normally cover it. World Health Organization criteria for population screening for genetic predisposition to disease are that the disease is an important public health burden in the target population; that the risk of disease due to mutations in the screened genes is known; and that effective intervention exist to reduce morbidity and mortality among genetically susceptible individuals. At present, the US Preventive Services Task Force (USPSTF) supports BRCA1 and BRCA2 testing based on family history and ancestry, but not for the entire female population, given the lack of data on risks for mutation carriers ascertained from the general population, rather than through a personal or family history of cancer. This position was correct based on the data then available. However, a just-completed study now provides evidence that supports offering BRCA1 and BRCA2 sequencing to all women. Population-based screening enables mutation carriers to be identified independent of physician referral or family involvement. This is important, because at present, there is marked variability in practice in following the USPSTF guidelines. A recent survey revealed that only 19% of US primary care physicians accurately assessed family history for BRCA1/BRCA2 testing. Population-wide screening will require significant efforts to educate the public and to develop new counseling strategies, but this investment will both save women s lives and provide a model for other public health programs in genomic medicine. Women do not benefit by practices that protect them from information regarding their own health. They should have the choice to learn if they carry an actionable mutation in BRCA1 or BRCA2. Therefore, the role of both gynecologists and oncologists to educate the population is cucial if we want to avoid that this process will be emotionally influenced by the media generating a new collective syndrome. Prof. Paolo Scollo S.I.G.O. President 7

8 FARMACEUTICAMEV IN GINECOLOGIA LA NATURA CHE AIUTA ClimaMEV IncontinenzaMEV VenaMEV FARMACEUTICA MEV - Strada Cassia Sud, Siena (SI) Tel / Fax

9 Laparoscopic radical hysterectomy with the use of SNAIL Tenaculum. A simplified uterine manipulator for the management of early cervical cancer Francesco Barletta 1, Giacomo Corrado 2, Enrico Vizza 2 1 Gynecology and Obstetrics Unit, San Giovanni-Addolorata Hospital, Rome, Italy 2 Gynecologic Oncology Unit, Regina Elena National Cancer Institute, Rome, Italy ABSTRACT Objective: To evaluate safety and efficacy of the SNAIL Tenaculum uterine manipulator (Simple Nebs Arising Incision Landmark) for total laparoscopic radical hysterectomy in early cervical cancer. Material and Methods: SNAIL Tenaculum uterine manipulator origin by a surgical reusable instrument named Uterine Tenaculum Forceps, model Schroder (code of Martin catalogue). It is modified adding two or four nebs 1-2 cm of distance from the tips of the instrument. We grasped the cervix with SNAIL Tenaculum and n order to preserve an adequate pneumoperitoneum during colpotomy surgical gloves are placed in vagina. Results: Twenty patients with early cervical cancer underwent total laparoscopic radical hysterectomy used SNAIL Tenaculum uterine manipulator. During surgery the nebs were always under vision and the median length of vagina removed was 21 mm. (range 10-40mm). None intra-operative complications were registered. Conclusion: We found SNAIL Tenaculum to be a safe and efficient tool with lowest cost so far recorded. It eliminated risks of perforation and LVS involvement, maintaining good uterine mobility. Also the nebs allow surgeon to choose the length of vaginal wall to be removed. Keywords: Simple Nebs Arising Incision Landmark; SNAIL Tenaculum uterine manipulator; laparoscopic radical hysterectomy; early cervical cancer SOMMARIO Obiettivi: Valutare la sicurezza e l efficacia della pinza da presa SNAIL Tenaculum come manipolatore uterino per l isterectomia radicale laparoscopica nel trattamento del cancro cervicale iniziale. Materiali e metodi: Lo SNAIL Tenaculum origina da uno strumento chirurgico riutilizzabile denominato Uterine Tenaculum Forceps, modello Schroder (codice del catalogo Martin degli strumenti chirurgici). Questa pinza fu modificata aggiungendo due o quattro rebbi, di 0.8-1cm di lungezza, a 1 o 2 cm di distanza dall estremità dello strumento. Prima dell intervento chirurgico, la cervice fu pinzata e chiusa con lo SNAIL Tenaculum e il pneumoperitoneo, durante la colpotomia circolare, fu mantenuto inserendo alcuni guanti chirurgici nella vagina. Risultati: 20 pazienti furono sottoposte a isterectomia radicale laparoscopica con l utilizzo dello SNAIL Tenaculum. Durante l intervento chirurgico i rebbi furono sempre evidenziati attraverso la parete vaginale anche nelle pazienti obese. La vagina rimossa fu mediamente di 21 mm (range, tra 10 e 40 cm) e nessuna complicazione intraoperatoria si verificò. Conclusioni: Lo SNAIL Tenaculum si rilevò un manipolatore uterino sicuro, valido e di basso costo eliminando i rischi di perforazione uterina e di coinvolgimento neoplastico degli spazi linfovascolari, mantenendo una buona mobilità uterina e permettendo al chirurgo di scegliere la lunghezza di vagina da asportare. INTRODUCTION The advantages of minimally invasive gynecologic surgery have been described more recently even for oncologic cases such endometrial and cervical cancer (1,4). In a review by the SGO Clinical Practice Endometrial Cancer Working Group for the Society of Gynecologic Oncology Clinical Practice Committee (5) it refers in recommendations : laparoscopy should be embraced as the standard surgical approach for comprehensive surgical staging in women with endometrial cancer (level of evidence: A). Also in cervical cancer FIGO stage IB1,IB2,IIB, multiple studies and trials support the advantages of laparoscopic approach (6,8). The procedure of Total Laparoscopic Radical Hysterectomy (TLRH) performed in these cases assume using of uterine manipulator. Correspondence to: Copyright 2014, Partner-Graf srl, Prato At present there is no standard recommendation for use of manipulators in the surgical treatment of endometrial and cervical cancer. Risk of perforation, LVS involvement and positive peritoneal cytology by uterine manipulation is still debated. Should also be considered the costs of uterine manipulators both reusable and disposable. We evaluate safety and efficacy of a modified tenaculum called SNAIL Tenaculum (Simple Nebs Arising Incision Landmark ) for laparoscopic radical hysterectomy in early cervical cancer. MATERIAL AND METHODS We prospectively collected data from patients with cancer of the uterine cervix in FIGO stage IB1. All patients underwent a type C1 laparoscopic radical hysterectomy plus pelvic 9

10 It. J. Gynaecol. Obstet. 2015, 27: N.1 lymphadenectomy, with the use of SNAIL Tenaculum like uterine manipulator. This invention origin by a surgical reusable instrument named Uterine Tenaculum Forceps, model Schroder, code of Martin catalogue. This tenaculum is modified adding two or four nebs 1-2 cm of distance from the tips of the instrument. The nebs are 0,8-1 cm each and widen with a 90 degrees angle between them. They can be perpendicular to main axis of instrument or forming with latter degrees angle bent forward (Figure 1). In order to preserve an adequate pneumoperitoneum during colpotomy surgical gloves are placed in vagina. Surgical technique No uterus manipulator devices were used, but the cervix were grasped with a SNAIL (Figure 2) and a iodine gauze with some gloves, depending by width of the vagina, were emplaced in vagina in order to preserve an adequate pneumoperitoneum during colpotomy. Figure 2: Cervix is grasped with a SNAIL Tenaculum 10 Figure 1: Simple Nebs Arising Incision Landmark (SNAIL) uterine manipulator Inclusion criteria were: good general condition, tumor size < 3 cm, no evidence of lymph node metastases in imaging study (MRI and/or CT and/or PET). BMI was not a considered an exclusion criterion. All patients were staged according the most recent FIGO clinical staging system (9). All patients received a bowel preparation preoperatively, and antithrombotic prophylaxis with subcutaneous low-molecular weight heparin. Approval to conduct the study was obtained independently from an internal review board at each participating institution. Clinical patient characteristics included age, body mass index (BMI), histopathological subtype, and tumour grade. Intraoperative parameters evaluation included operative time, complications, and blood loss. Blood transfusions were administrated if Hb value was 7 g/l. Postoperative parameters included short-term (within 30 days of the procedure), and longterm complications (more than 30 days after the procedure); moreover, status of the surgical margins, status and number of pelvic lymph nodes removed, length of dissected vagina, width of bilateral parametrium were evaluated, along with length of hospitalization, time to recovery of normal bladder function. The first step of our technique consist of open the all retroperitoneal spaces according to the following sequence: paravescical space, pararectal lateral space (Latzko), pararectal medial space (Okabayashi), rectovaginal space and vescicovaginal space. The second step is the en bloc level 1 and level 2 pelvic lymphadenectomy according to Queleu and Morrow classification (10). Para-aortic lymphadenectomy is not routinely performed unless suspicious pelvic lymph nodes are confirmed to have metastatic disease on frozen section evaluation in order to determine the field of postoperative radiation. Afterwards, type C1 radical hysterectomy was performed as described by Querleu and Morrow. During surgery, we used an advanced multifunctional ultrasounds instrument (Ethicon Harmonic Ace curved shears ) to dissect, cut and coagulate. In young patients whose ovarian function needs to be preserved, the ovaries are transposed laterally to the para-colic gutters and fixed securely to the abdominal wall, or else the ovaries are moved from the infundibulopelvic vessels with a caution of the ureter. After a careful control of blood loss, to minimize the risk of port site metastases, the vagina prior to removal of the ports and all the ports sites are irrigated with 5% povidine iodine solution prior to completion of the surgery. In all patients the urine catheter is removed 3 days after

11 F. Barletta et al. operation and an intermittent self catheter is used for voiding until the residual urine volume is less than 100 ml. RESULTS From Jannuary 2013 to December 2014, twenty patients were included into the study. The median age was 46 years (range, 25 65), median BMI was 24 kg/m2 (range, kg/m2). There were not conversion to abdominal surgery and all patients underwent total laparoscopic radical hysterectomy (type C1) and pelvic lymphadenectomy (Table I). Table I: Clinical characteristics of the 20 women with early cervical cancer underwent TLRH with pelvic lymphadenectomy with use of SNAIL manipulator Characteristics Patients Median Age (years) 44 (19-72) Median BMI (kg/m 2 ) 24 (16-34) Median tumour size (mm) 15 (10-30) Previous abdominal surgery 10 (50%) Histology Squamous Adenocarcinoma Grading G1 G2 G3 13 (65%) 7 (35%) 1 (5%) 8 (10%) 11 (55%) The surgical outcomes are summarized in Table II. The median operating time was 188 minutes (range, minutes) with no limitation of BMI. The median blood loss was 240 ml (range, ml); none of the patients required intraoperative blood transfusion, while two patients had a postoperative blood transfusion. The median number of removed pelvic lymph nodes was 21 (range, 10 37). Five squamous cell carcinoma and one adenocarcinoma patients had a total of 9 positive pelvic nodes at frozen section. In these patients, lymphadenectomy was extended to the para-aortic nodes, with negative specimens. The superior border of the dissection in the para-aortic lymphadenectomy was the inferior mesenteric artery and the median number of removed para-aortic lymph nodes was 7 (range, 5 11). The median length of dissected vagina was 21 mm (range, mm). The median width of parametrium was 24 mm on the right side (range, mm) and 25 mm on the left side (range, 15 50). The surgical margins were free of disease in all cases. Table II: Surgical outcome of the 20 patients with early cervical cancer operated by TLRH with pelvic lymphadenectomy with use of SNAIL manipulator Characteristics TRRH Median operative time (min) 188 ( ) Median blood loss (ml) 240 (30 480) Median pelvic lymph nodes 21 (10 37) Median width right parametrium (mm) Median width left parametrium (mm) 24 (10 50) 25 (15 50) Median length vaginal cuff (mm) 21 (15 45) Major intraoperative complications Major early postoperative complications Major late postoperative complications 1 (5%) 2 (10%) 9 (25%) Blood transfusion 2 (10%) Conversion to laparotomy 0 Reoperation 0 Median hospital stay (days) 4 (2 10) There was one intra-operative complication: one patient had injury of the left hypogastric vein and promptly repaired during the same laparoscopic surgery with a total blood loss of 480 ml. She needed a post operative of blood transfusion. There were two postoperative short term complications: in one case postoperative pelvic bleeding was successfully recovered by drainage; the other woman suffered from lymphocyst on the 10th day post-operation. The median hospital stay was 4 days (range, 3 10 days). The self catheter commenced postoperatively from day 3. The time to resumption of normal bladder function ranged from 10 days to 3 months. Four patients treated with radiation therapy and three with chemoradiation plus brachytherapy showed a worsening in condition. Long term complications were: 2 patients suffered urinary incontinence; 2 patients had constipation, while other 1 patient had dyspareunia. Of these 5 patients, 3 patients had undergone further radiotherapy. Adjuvant therapy was administrated in 10 patients. Six patients, with pelvic lymph nodes metastasis, underwent adjuvant radiochemotherapy. Four patients underwent adjuvant radiotherapy for lymph-vascular space invasion (LVSI) and high grade lesion. 11

12 It. J. Gynaecol. Obstet. 2015, 27: N.1 12 The median follow-up was 12 months (range, 3 27) and although our median follow-up is still less than 3 years of survival, all patients are alive without disease. DISCUSSION Most gynecologic surgeons appreciate the advantages of uterine manipulation during hysterectomy procedures because of the improved visualization of key anatomic structures throughout the dissection. However there have been concerns that uterine cancer pathology may be altered (increased LVSI) from uterine manipulators (11,13) and some investigators choose not to use manipulators in cervical cancer (14,16) without mentioning the risk of perforation and positive peritoneal cytology. In a prospective randomized clinical trial about effects of uterine manipulation on surgical outcomes in laparoscopic management of endometrial cancer (17) the authors did not find an increase rate of positive peritoneal cytology or lymphovascular space invasion after using of a uterine manipulator. Subsequently on International Journal of Gynecological Cancer appeared a comment (18) on Lee paper showing some limitations of the study. Between them the uterine manipulator was inserted after ligation of both the fallopian tubes so one would not expect to find endometrial cancer cell spillage. Moreover the risk of perforation when using a uterine manipulator in endometrial cancer patients was not mentioned. This may reflect publication bias of relatively rare complications. In patients with deep myometrial invasion this may be important. Since that over 70% of the included patients have less than 50% myometrial invasion, this study may be underpowered to detect differences in recurrence. Larger series are necessary to confirm the findings as well as the risks of perforation on outcome. At present there is no standard recommendation for use of uterine manipulators in the surgical treatment of endometrial and cervical cancer. The influence on both surgical and oncological outcome using the already known uterine devices is unclear. The risk of perforation, lympho-vascular spaces (LVS) involvement and positive peritoneal cytology by uterine manipulation is still debated. A uterine manipulator performs the following functions: manipulates the uterus stretching the side being operated upon and brings the uterus closer to the surgical laparoscopic instruments facilitating the procedure; increases the distance between the uterus and bladder, ureters, rectum thus reducing the chance of injury; facilitates identification of the vaginal cuff just below the cervical attachment; pulls the uterus vaginally after its complete detachment and maintains the pneumoperitoneum following colpotomy. An ideal uterine manipulator to perform TLRH in endometrial or cervical cancer should have the following characteristics: easy to assemble, inexpensive, does not fragment or break down into pieces during the procedure, none risk of perforation, has a good range of mobility and mobilizes the uterus in anteversion, retroversion and lateral movements, should close external uterine orifice to avoid endometrial cells leakage in vagina, facilitates identification of the vaginal cuff choose the length of vaginal wall to be removed modulating, proximally or distally, the incision line. There are many uterine manipulators available; some manipulators are reusable (ideal), some are disposable and some are partially disposable and partially reusable such that the tips are disposable but the handle is reusable. Complications attributable to the use of uterine manipulators include cervical lacerations, uterine perforation, laceration of the uterine vessels, retroperitoneal or intraperitoneal bleeding, perforation of the bowel, rectum or bladder, ascending infection, interruption of unsuspected intrauterine pregnancy and retention of part of the manipulator as a foreign body. In oncologic cases we were looking for something which doesn t stress the inner surface of the uterus, without any pushing or squeezing the endometrium and the cervical canal, which are the sites of neoplasm, and without any possible leakage of neoplastic cells in vagina. So the solution for our needs was close our eyes. We did a simple modification of an instrument very familiar and used by gynecologists worldwide: a surgical reusable instrument named Uterine Tenaculum Forceps, model Schroder, code of Martin catalogue. This tenaculum is modified adding two or four nebs 1-2 cm of distance from the tips of the instrument. The nebs are 0,8-1 cm each and widen with a 90 degrees angle between them. They can be perpendicular to main axis of instrument or forming with latter degrees angle bent forward in order to respect the different angle of the posterior fornix, despite the anterior, with the vagina. The nebs expose very clearly the vagina for colpotomy and allow surgeon to choose the length of vaginal wall to be removed modulating, proximally or distally

13 F. Barletta et al. to them, the incision line. In some patients, not included in the study, the SNAIL Tenaculum has poor chances to fix the uterus since the disappearance of the cervix after amputation or radiochemotherapy (RTCT). We found SNAIL Tenaculum to be a safe and efficient tool for patients who undergoing TLRH since it eliminates risks of perforation, LVS involvement and positivization of peritoneal cytology, maintaining good chances of uterine mobility. Also the nebs allow surgeon to choose the length of vaginal wall to be removed. Last, but not least, must be said SNAIL Tenaculum combines the ease of use of a very familiar instrument to gynecologists, widespread at all latitudes, with the lowest cost so far recorded. COMPETING INTERESTS The authors report no conflicts of interest. The authors are responsible for the content and writing of the paper. REFERENCES 1) Palomba S, Falbo A, Mocciaro R, Russo T, Zullo F. Laparoscopic treatment for endometrial cancer: a meta-analysis of randomized controlled trials (RCTs). Gynecol Oncol.2009;112: ) Gaia G, Holloway RW, Santoro L, Ahmad S, Di Silverio E, Spinillo A. Robotic-assisted hysterectomy for endometrial cancer compared with traditional laparoscopic and laparotomy approaches: a systematic review. Obstet Gynecol 2010; 116: ) Lu D, Liu Z, Shi G, Zhou X. Robotic assisted surgery for gynaecological cancer. Cochrane Database Syst Rev 2012;18:1 4) Ramirez PT, Adams S, Boggess JF, Burke WM, Frumovitz MM, Gardner GJ, Havrilesky LJ, Holloway R, Lowe MP, Magrina JF, Moore DH, Soliman PT, Yap S. Robotic-assisted surgery in gynaecologic oncology: a Society of Gynecologic Oncology Consensus Statement Developed by the Society of Gynecologic Oncology s clinical Practice Robotics Task Force. Gynecol Oncol 2012;124: ) SGO Clinical Practice Endometrial Cancer Working Group. Endometrial cancer: a review and current management strategies: Part I. Gynecol Oncol 2014;134, ) Ghezzi F, Cromi A, Ditto A, Vizza E, Malzoni M, Raspagliesi F, Uccella S, Corrado G, Cosentino F, Gotsch F, Martinelli F, Franchi M Laparoscopic Versus Open Radical Hysterectomy for Stage IB2-IIB Cervical Cancer in the Setting of Neoadjuvant Chemotherapy: A Multi-institutional Cohort Study. Ann Surg Oncol. 2013; 20(6): ) Pellegrino A, Vizza E, Fruscio R, Villa A, Corrado G, Villa M, Dell'anna T, Vitobello D. Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in patients with Ib1 stage cervical cancer: Analysis of surgical and oncological outcome. Eur J Surg Oncol. 2009; 35(1): ) Vizza E, Pellegrino A, Milani R, Fruscio R, Baiocco E, Cognetti F, Savarese A, Tomao F, Chen C, Corrado G. Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in locally advanced stage IB2-IIB cervical cancer patients after neoadjuvant chemotherapy. Eur J Surg Oncol. 2011;37(4): ) Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix and endometrium. Int J Gynaecol Obstet 2009;105(2): ) Querleu D,Morrow CP. Classification of radical hysterectomy. Lancet Oncol.2008; 9(3): ) Kitahara S, Walsh C, Frumovitz M, Malpica A, Silva EG. Vascular pseudo-invasion in laparoscopic hysterectomy specimens for endometrial carcinoma: a grossing artifact? Am J Sur Pathol 2009;33: ) Logani S, Herdman AV, Little JV, Moller KA. Vascular Pseudo-invasion in laparoscopic hysterectomy specimens: a diagnostic pitfall. Am J Sur Pathol 2008; 32: ) Krizova A, Clarke BA, Bernardini MQ, James S, Kalloger SE, Boerner SL, Mulligan AM. Histologic artefacts in abdominal, vaginal, laparoscopic, and robotic hysterectomy specimens : a blinded, retrospective review. Am J Surg Pathol 2001; 35: ) Shafer A, Boggess JF. Robotic-assisted endometrial cancer staging and radical hysterectomy with the Da Vinci surgical System. Gynecol Oncol 2008; 111(Suppl.2): ) Estape R, Lambrou N, Diaz R, Estape E, Dunkin N, Rivera A. A case matched analysis of robotic radical hysterectomy with lymphadenectomy compared with laparoscopy and laparotomy. Gynecol Oncol 2009; 113: ) Magrina J, Kho R, Magtibay PM. Robotic radical hysterectomy: technical aspects. Gynecol Oncol 2009; 113: ) Lee M, Kim YT, Kim SW, Kim S, Kim JH, Nam EJ. Effects of uterine manipulation on surgical outcomes in laparoscopic management of endometrial cancer: a prospective randomized clinical trial. Int J Gynecol Cancer. 2013;23(2): ) Smid AT, Piek JM, Pijnenborg JM. Comments on "Effects of uterine manipulation on surgical outcomes in laparoscopic management of endometrial cancer: a prospective randomized clinical trial". Int J Gynecol Cancer. 2013;23(6):980 13

14 14 It. J. Gynaecol. Obstet. 2015, 27: N.1

15 Vaginal Erbium Laser: the Second Generation Thermotherapy for the Genitourinary Syndrome of Menopause (GSM) in Breast Cancer Survivors. A preliminary report of a pilot study Marco Gambacciani 1, Marco Levancini 1, 2 1 Department of Obstetrics and Gynecology, Pisa University Hospital 2 Department of Obstetrics and Gynecology, Clinica Alemana, Universidad Del Desarrollo, Santiago. Chile ABSTRACT This is a preliminary report of a pilot study aimed to assess the effectiveness and safety of vaginal erbium laser in the treatment of Genitourinary Syndrome of Menopause (GSM) in postmenopausal breast cancer survivors. GSM symptoms were assessed before and after three applications of erbium laser in 13 women, using subjective (visual analog scale) and objective (Vaginal Health Index Score, VHIS) measures. Vaginal Erbium laser treatment was effective to improve GSM symptoms. Both subjective and objective scores significantly improved in comparison with baseline values ( p <0.01). No adverse events were recorded during the study period. This preliminary results suggest that Vaginal Erbium Laser is effective and safe for the treatment of GSM in postmenopausal Breast Cancer Survivors. SOMMARIO Il lavoro riporta una analisi preliminare di uno studio pilota condotto per valutare efficacia e sicurezza del trattamento con laser Erbium vaginale della sindrome genitourinaria della menopausa (Genitourinary Syndrome of Menopause, GSM) in donne in postmenopausa dopo trattamento per una carcinoma della mammella. I sintomi sono stati valutati in 13 donne, usando scale per la valutazione soggettiva (VAS, visual analog scale) e oggettiva (Vaginal Health Index Score, VHIS). Il trattamento con laser Erbium vaginale è risultato capace di ridurre la sintomatologia della GSM. Sia gli score soggettivi che quelli oggettivi hanno mostrato un significativo miglioramento rispetto ai valori basali ( p <0.01). Non sono stati riscontrati eventi avversi durante lo studio. In conclusione, questi risultati preliminari suggeriscono che il con laser erbium possa rappresentare una alternative efficace e sicura per il trattamento della GSM in donne in postmenopausa dopo Carcinoma della Mammella. Keywords: Menopause, Estrogen, Erbium Laser, Genitourinary Syndrome of Menopause, Breast Cancer Survivors INTRODUCTION The genitourinary syndrome of menopause (GSM) may affect up to 50% of postmenopausal women and their symptoms tend to be progressive, jeopardizing the quality of life and sexual relationships (1-3). Local hormone replacement therapy (HRT) is the treatment of choice (2-5). However, many women have contraindications, such as a history of estrogen-dependent tumors, particularly endometrial cancer and breast cancer (2-5). No single agent can globally ameliorate the quality of life of breast cancer survivors, coping with menopausal symptoms. Particularly, specific studies on GSM treatment in breast cancer survivors are scarce. Laser technology is currently widely used with positive effects demonstrated on basic and clinical studies on tissue remodeling, collagenogenesis and angiogenesis (6-8). The different types of lasers have different physical Correspondence to: Copyright 2014, Partner-Graf srl, Prato characteristics that determine specific effects on tissues. Recently in a pilot study, Salvatore et al. (9) demonstrated that treatment with fractionated CO2 laser induced a significant improvement of the GSM in postmenopausal women. The aim of this study is to evaluate the short-term efficacy and acceptability of a second generation of vaginal laser treatment, using an erbium laser crystal yttrium-aluminum-garnet (Er: YAG) as a non-ablative photothermal therapy for the management of GSM in breast cancer survivors. MATERIAL AND METHODS This is a pilot study, conducted in women attending menopause clinic of Pisa University Hospital with an history of treated breast cancer and suffering from GSM. All patients gave written informed consent. The protocol was revised by an National Independent Advisory Board and approved by the Ethics Committee of the Department of Obstetrics and Gynecology. The 15

16 It. J. Gynaecol. Obstet. 2015, 27: N.1 16 procedures followed were in accordance with the ethical standards of the Committee on Institutional human experimentation, and with the Helsinky Declaration of 1975, as revised in Inclusion criteria were the presence of GSM in women with plasma levels of gonadotropin and estradiol in postmenopausal range (FSH> 40 U/L; estradiol <25 pg/ml) and negative PAP smear. Exclusion criteria were: lesions, scars or infection active or recents (30 days) of the genitourinary tract; abnormal uterine bleeding; use of lubricants or any other local preparation within 30 days prior inclusion to study; history of photosensitivity disorder or use of photosensitizing drugs; genital prolapse (grade II-III classification POP-Q); serious or chronic illness that could interfere with the fulfillment of the study; and have been treated with hormones or other medications to relieve menopausal symptoms in the previous 3 months. In this preliminary report, we show the results of patients suffering from severe GSM after a successful treatment for breast cancer. All patients women were treated with Erbium laser (XS Fotona Smooth, Fotona, Ljubljana, Slovenia) with a wavelength of 2940 nm. The diameter of the laser spot size was 7 mm, with a pulse according to the SMOOTH mode at a frequency of 1.6 Hz, and fluence (laser energy emitted per unit area) of 6.0 J/cm 2. The procedures were performed on an outpatient basis without anesthesia or drug use before or after the intervention. The treatment protocol consists of 3 laser applications every 30 days (L1, L2, L3) with a visit 2-4 weeks before treatment (V0) and a follow-up visit 4 and 12 weeks after the last application. After treatment, patients are recommended to have sexual abstinence for one week. Subjective symptoms (vaginal dryness and dyspareunia) were assessed using a visual analogue scale (VAS) at each visit (range 0-10, 0 = total absence of symptom and 10 cm = worst symptom) and the Vaginal Health Index Score (VHIS) was calculated. VHIS evaluates the aspect of the vaginal mucosa (elasticity, ph, vaginal discharge, mucosal integrity and moisture). These parameter were evaluated at baseline (T0), after the first (L1), second (L2) and third (T3) laser treatments, as well as after 4 (T+4) and 12 (T+12) weeks after the last laser treatment. Each parameter is graded from 1 to 5 being atrophic a total score 15 (10). In the post-treatment control, acceptability of therapy was asked, describing it as: excellent, good, fair, bad or unacceptable. Patients who leave the study before the deadline were considered dropouts. This is an interim report, of an ongoing study the sample size was not based on a statistical rationale. Data are presented as mean and standard deviation. Continuous variables were analyzed using the ANOVA for repeated measures and the Wilcoxon sign-rank test. Data were analyzed using StatView version 2.5 software (SAS Science, Chicago, IL, USA). RESULTS Table I show demographic characteristics of patients included in the study. Table I. Baseline characteristics of the breast cancer survivors (n=13) included in the study. Mean DS Min-Max Age Age at menopause Years since menopause Vaginal dryness and dyspareunia scores showed a progressive decrease after 1st, 2nd and 3rd treatment (p<0.01, Figure 1).. The results were maintained during the follow up, after 4 and 12 weeks from the last laser treatment (p<0.01, Figure 1). Figure 1. Effect of second generation laser thermotherapy on Dryness and Dyspareunia scales (10-point scale, cm) in 13 postmenopausal breast cancer survivors (* p< 0.01 vs basal values). See text for details. Conversely, VHIS values showed a significant increase during the treatment, and the results were maintained after 4 and 12 weeks from the last laser treatment (p<0.01, Figure 2). No adverse events related to the procedure were recorded throughout the study period. No patients dropped out from the study.

17 M. Gambacciani et al. Figure 2. Effect of second generation laser thermotherapy on Vaginal Health Index Score (VHIS) in 13 postmenopausal breast cancer survivors (* p< 0.01 vs basal values). See text for details. DISCUSSION The analysis of this preliminary study indicates that the second generation vaginal thermotherapy using Erbium laser is effective and safe for the treatment of GSM in postmenopausal breast cancer survivors. The results obtained in this small series of patients indicate that this method is practical, seems to be well accepted and not related to adverse events. In these particular set of patients the vaginal erbium laser improved the most bothersome symptoms, just after the first application of laser. Similar results were previously reported in normal postmenopausal women using either the Erbium laser (11), and the CO2 laser (9). These preliminary, short term results show that treatment with vaginal Erbium laser in breast cancer survivors suffering from severe GSM is feasible, effective and safe in the short term. Further studies are needed to evaluate the effectiveness and the safety of vaginal erbium laser treatment. If these results will be confirmed in properly sized and long-term studies, we will have a safe and effective option to treat GSM in women presenting contraindication to postmenopausal hormone use. AKNOWDLEGMENTS The AA express their thanks to the Members of National Independent Advisory Board, Prof Nicoletta Biglia, Torino; Prof. Rossella Nappi, Pavia; Prof. Anna Maria Paoletti, Cagliari, for their excellent work in revising the protocol. REFERENCES 1) Portman D. J. and Gass M. L. S. on behalf of the Vulvovaginal Atrophy Conference Panel. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women s Sexual Health and The North American Menopause Society. Climateric 2014; 17 (5): ) Sturdee D W, Panay N. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010; 13 (6): )Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013; 20: )Santen RJ, Allred DC, Ardoin SP, et al. Executive summary: Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010 ; 95 (Suppl 1) : s1 66 5) De Villiers T. J., A. Pines, N. Panay, M. Gambacciani, D. F. Archer, R. J. Baber, et al., on behalf of the International Menopause Society. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climateric 2013; 16: ) Kaufmann R, Hibst R. Pulsed Erbium:YAG laser ablation in cutaneous surgery. Lasers Surg Med. 1996;19(3): ) Levy JL, Trelles MA. New operative technique for treatment of xanthelasma palpebrarum: laser inverted resurfacing: preliminary report. Ann Plast Surg Apr; 50(4): ) Vizitin Z., Novel Minimally Invasive VSPEr:YAG Laser Treatments in Gynecology, J. LAHA, Vol. 2012, No.1; pp ) Salvatore S, Nappi R E, Zerbinati N, Calligaro A, Ferrero S, Origoni M, et al. A 12-week treatment with fractional CO 2 laser for vulvovaginal atrophy: a pilot study. Climacteric 2014;17:1 7 10)Bachmann GA, Notelovitz M, Kelly SJ, et al. Longterm nonhormonal treatment of vaginal dryness. Clin Pract Sexuality 1992 ; 8 : ) Gaspar A. Comparison of New Minimally Invasive Er:YAG Laser Treatment and Hormonal Replacement Therapy in the treatment of Vaginal Climacteric 2014;17(Suppl 1):48 108, P

18

19 New therapeutic strategies in short cervical length: Arabin pessaries Lucio Juliano 1, Fabiana De Benedictis 2, Teresa Guarino 1, Maria Giovanna Schiattarella 3 Studio Aldati Napoli 1 A.O. A. Cardarelli Napoli (ITA) 2 A.O. S. Jacopo Pistoia (ITA) 3 A.O. M. Bufalini Cesena (ITA) ABSTRACT The progress made in the field of ultrasound in the diagnosis of threatened preterm delivery in the case of short cervical length (SCL) are unfortunately not paid advances in therapy, since actual treatment options are confined to the use of progesterone, micronized vaginally or orally, of antibiotics and indomethacin, which are also used vaginally or orally, of nifedipine, used orally, until reaching to promising use of lactoferrin or lactoglobulin, vaginally, or to the packaging of a surgical cerclage procedure now almost obsolete in most European countries because of the many complications that occurred. New perspectives seems to offer the application of silicone vaginal devices specifically designed to modify the cervical plasticity and reduce, with very striking mechanism as will be seen, the possibility of occurrence of segmental uterine contractions; for such features to cervical support such devices are called pessaries, whose function is mistakenly equated with classic surgical cerclage, invasive method, bloody, costly and much less effective in preventing preterm birth. Our experience is based on the application of 32 vaginal devices in the period October May 2014; of these 28 (p=87.5%) were placed in singleton pregnancies and 4 (12.5%) in twin pregnancies (3 bigemine pregnancies 1 and triplets). In 22/32 pregnant women (p=69%) the application of the pessary has been associated with the use of a medicament, as we shall see later in the specification, while in 10/32 (p=31%) was not associated with any medication. Surprisingly, the outcome of these 2 latter groups did not show substantial changes, so as to lead us to believe that the action of vaginal device is the real creator in obtained benefits. Last notation must be made on gestational period of positioning pessary that in the vast majority of cases occurred between 22 and 28 weeks (n=29, p=90%), while in only 3 cases (p=10%) the time of insertion was greater than 28 weeks. Almost all pregnant women had when inserting a BMI> 25 (n=30, p=94%), while only 2 were 25. Keywords: Arabin pessary, Flabby Cervix, Short Cervix, Preterm Delivery, Premature Rupture Of Membranes, Non-invasive cerclage SOMMARIO Ai progressi compiuti in campo ecografico nella diagnosi di minaccia di parto pretermine (MPP) nei casi di short cervical lenght (SCL) non sono purtroppo corrisposti progressi in campo terapeutico, dal momento che le opzioni terapeutiche ad oggi applicate sono confinate all utilizzo di progesterone, micronizzato per via vaginale o per via orale, di antibiotici e di indometacina, anch essi utilizzati per via vaginale o per via orale, alla nifedipina, utilizzata per via orale, al promettente utilizzo di lattoferrina o lattoglobulina, per via vaginale, e/o al confezionamento di un cerchiaggio chirurgico, procedura ormai quasi in disuso nella stragrande maggioranza dei Paesi Europei a causa delle numerose complicanze riportate. Nuove prospettive in tal senso sembra offrire l applicazione di dispositivi vaginali in silicone specificamente progettati per modificare la plasticità cervicale e ridurre, con meccanismo molto suggestivo come si vedrà, la possibilità di insorgenza di contrazioni segmentarie uterine; per tali funzioni di supporto cervicale tali dispositivi sono denominati pessari, la cui funzione è erroneamente assimilata al classico cerchiaggio chirurgico, metodica invasiva, cruenta, costosa e molto meno efficace nel prevenire il parto pretermine. La nostra esperienza personale si basa sull applicazione di 32 dispositivi vaginali nel periodo ottobre maggio 2014; di questi 28 (p=87.5%) sono stati posizionati in gravidanze singole e 4 (12.5%) in gravidanze gemellari (3 gravidanze bigemine e 1 trigemina). In 22/32 gravide (p=69%) l applicazione del pessario è stato associato all utilizzo di un medicamento, come poi vedremo nella specifica, mentre in 10/32 (p=31%) non è stato associato alcun farmaco. Sorprendentemente l outcome tra questi 2 ultimi gruppi non ha mostrato sostanziali variazioni, tanto da indurci a ritenere che l esclusiva azione del dispositivo vaginale sia il reale artefice dei benefici ottenuti. Ultima notazione va fatta sull epoca gravidica di posizionamento del pessario che nella stragrande maggioranza di casi è avvenuto tra la 22 a e la 28 a settimana (n=29 p=90%), mentre in soli 3 casi (p=10%) l epoca di inserimento è stata maggiore delle 28 settimane. Quasi tutte le gravide presentavano all atto dell inserimento un BMI>25 (n=30 p=94%), mentre solo 2 erano 25. INTRODUCTION The threatened preterm delivery, or SPB (Spontaneous Preterm Birth), is a syndromic disease that recognizes a variety of causes. Almost 100 years the pessaries have been successfully used in genital prolapse treatment (4,6,8,42). Different types of pessary have succeeded over the years, from the classic ring pessaries (Figure 1) to Donut Correspondence to: pessaries (Figure 2), by Hodge pessary (Figure 3) to Jorde-Hamann pessaries (Figure 4 ), all used in the symptomatic treatment of genital prolapse and therefore not very considered by gynecologists with higher surgical inclinations that saw, and in some cases can still be seen today, in the packaging of surgical cervical cerclage the only successful attempt to oppose the SPB, regardless of the many failures and multiple complications obtained. Copyright 2014, Partner-Graf srl, Prato 19

20 It. J. Gynaecol. Obstet. 2015, 27: N.1 Figure 1. Ring Pessary. Figure 2. Donut Pessary Figure 3. Hodge Pessary Figure 4. Jorde-Hamann Pessary 20 In 1979 the german gynecologist Hans Arabin devised a flexible silicon device which is well suited to the natural shape of the vaginal fornices, with a circular central space to permit the entire cervix to be included and therefore supported and angulated in a position more suited to the physiological hereinafter of pregnancy. Just this latter point has been to intuition of dr. Arabin, which assumed that he must not forcibly close the cervical canal, the principle on which is based the surgical cerclage, but restore to the cervix the natural angle with the uterine body to ensure that it interrupted the inevitable evolution towards the onset of contractions that ultimately led to preterm delivery. As indeed it himself wrote in his publication Pessartherapie (Gynäkologie ed. Thieme 1991, ),..the body of the uterus and cervix are 2 entities histologically and functionally different, so different that they can be considered as two bodies which form part of the same apparatus; must be maintained an angulation between 30 and 45 degrees, a prerequisite to the physiological continuation of the pregnancy. In the moment in which this angle is lost, resulting in straightening of the cervix with respect to the body, it triggers a process that ultimately leads to the onset of uterine contractions, almost like a trigger of a mine that is activated when fit together 2 ends normally separate [..].Therefore the Arabin pessary was designed with the intent not only to hold and squeeze the cervix, but especially to tilt the cervix and rotate it slightly toward the sacred (Figure 5). Only with the advent of transvaginal sonography has been documented effectively reducing or at least stabilizing the cervical funneling after placement of Arabin pessary in selected patients (2,10,25,26,27,29,30,33,37,39,42) (Figure 6). There are several hypotheses regarding Arabin pessary purpose in the prevention of premature rupture of membranes (PROM) and then ultimately prevent the spontaneous preterm birth (SPB) (4,7,8,9,11,12,13,14,20,25,28,40). The evidence which is the starting, documented by studies performed with transvaginal ultrasound (TVS) and with magnetic resonance (RMI), is that the Arabin pessary restores the normal utero-cervical angle, which so it remains until the device stand in place. Figure 5. Arabin pessary and its positioning. The first consequence of this modification is that it removes the direct pressure of amniotic fluid on the membranes covering the internal uterine orifice (IUO), preventing further cervical dilation triggered by the dissociation between amnion and chorion especially when pregnant is in the upright position (2,3,4,7,8,9,11,12,13,14,16). It 'also been postulated that genetically determined factors make the amniotic membranes more susceptible to mechanical stress or infection, for which the effect of the device would suffer from subjective factors not quantifiable. Another interesting hypothesis, advanced by N. Becher in 2009 and taken up by DC Lee in 2011 (18,19), is that the device prevents the mobilization of so-called "mucous plug", much studied issue actually, which seems play a very important role in the maintenance of pregnancy because, due to its unique protein structure and

21 L. Juliano et al. Figure 6. Large cervical funneling (U-shaped) reduced by positioning of Arabin pessary immunological capacity would responsible for protecting the uterine cavity by inflammatory and ascending infectious liables for initiation of preterm labor or PROM; it is well known that expulsion of the mucous plug a few hours preceding the onset of spontaneous labor in pregnant women at term. In a study of 2013, Cannie MM demonstrated with MRI aid that more time stationing the pessary and more greater the chances that the cervix will generates focal thickening and edema phenomena, which could complicate the dynamic changes of the cervix during labor (15). For those headings it is advisable to establish the cut-off tolerance average is 15 weeks, reserving to periodic checks of local conditions any greater permanence. In February of 2013 A. Baschat (pers. com.) has suggested that the pessary may decrease so-called Ferguson reflection, positive feedback that triggers when the cervix or vaginal walls pressure increases inducing production of oxytocin by the hypothalamicpituitary axle (41). Whatever the actual mechanism of pessary action, it is very important to evaluated the correct size to be placed. There are several sizes of Arabin pessary, and it s important to stick to pragmatic criteria in the choice of device that may be specifically adapted to peculiar characteristics of each specific patient. The latest generation devices are made in soft silicone with multiple circumferential perforations that allow secretions outflow that accumulates in the fornices, but the factor that distinguishes them is exclusively the size. The proximal hole diameter varies from 32 to 35 mm, while distal hole diameter goes from 65 to 70 mm; the height can be of and 30 mm. In general a size of 32 mm is used when the pessary is applied during the first trimester of singleton pregnancy or after surgical conization or even in the second and third trimesters without significant cervical funneling (Y-shaped) (9,16,25,42). In pregnants with large and edematous cervix or wide cervical funneling (U-shaped or V-shaped) is preferred devices with inner hole of 35 mm in order to avoid increases in focal pressure on the membranes and the release of prostaglandins during placement. Moreover, in physically smaller woman or nulliparous is advisable an outer diameter of 65 mm, to reserving 70 mm in constitutionally large patients or in multiparous. About the height of the Arabin pessary is advisable to use the small sizes of mm in singleton pregnancies, the 25 mm in pregnants with uterine distension (multiple pregnancies and/or polyhydramnios), and finally the 30 mm in patients with uterine prolapse during pregnancy (Table I). It s guessed that greater is device diameter and the more frequently the pregnant may complain of discomfort, due to distension of fornices operated from normal secretions which inevitably accumulate behind the pessary; this problem has been largely overcome to use of drilled devices (1,7,11,12,13,14,20,25,28,30,31,32,34,42). 21

22 It. J. Gynaecol. Obstet. 2015, 27: N.1 Table I. Sizes of Arabin pessaries Proximal hole diameter Distal hole diameter Height (mm) Clinical state 32 mm 35 mm 65 mm 70 mm Short or Flabby cervix at II trimester 25 mm Singleton Pregnancy o With or without Y-shaped funneling Nulliparous o o o Pluriparous o o o o With V- or U-shaped funneling (Flabby cervix) Nulliparous o o o Pluriparous o o o Twins o Without funneling Nulliparous o o o Pluriparous o o o o With V- or U-shaped funneling (Flabby cervix) Nulliparous o o o Pluriparous o o o Short or Flabby cervix at I trimester or after surgical conization o Singleton Pregnancy Nulliparous o o o Pluriparous o o o o Twins Nulliparous o o o Pluriparous o o o o With genital prolapse Nulliparous o o o Pluriparous o o o 22 Some considerations should be taken prior to placement of vaginal device, regardless of type and size used. We have to carefully evaluate the cervical characteristics by transvaginal ultrasonography (TVS). (10,14,16,22,23,26,29,30,37,39,42) The cut-off of 25 mm so far considered in the definition of short cervix should not be the only discriminating; this parameter might not be to treatment if just isolated finding in gestational age 32 weeks in nulliparous with singleton pregnancy, while it might be an adequate criterion when combined with funnelling cervix and/or cervical hypoechoic pattern. In our experience, lowest is cervical echogenicity and worst is the prognosis in terms of progression to generalized cervical incompetence that led to the triggering of preterm labor for activation of Ferguson reflection. The reasons should be sought in the histological characteristics of the cervix, very poor in muscle fibers which, due to prostaglandins release secondly oxytocic effect of Ferguson reflection, loosen increasing distance between them and making the ultrasound cervical pattern objectively less compact, just hypoechoic. So rather than using short cervix as a marker, we propose to introduce the term of flabby cervix to define by ultrasound (TVS) a cervical length 25 mm with hypoechoic parenchymal pattern and funneling (Y, U or V-shaped). Essential aspect to consider prior to placement of the pessary is the lack of previous vaginal infections by performing a vaginal swab, which excludes the presence of Chlamydia, β-hemolytic Streptococcus, Mycoplasma spp and Candida albicans, Gardnerella and Trichomonas. The secretions which inevitably accumulates in fornices where is placed the Arabin pessary, if copious may creates focal increases of pressure responsible for the Ferguson reflection, with increased risk of amnionitis and PROM (1,2,3,7,14,17,24,25,34,38). To complete prevention against vaginal infections, the pessary should be covered with antibacterial

23 L. Juliano et al. cream before insertion, also for lubricant effects that facilitates the positioning and minimizes the discomfort complained of by pregnant. There is no need to use anesthetics or analgesics (42), partly because the sensations reported by all patients at approximately 30 minutes from the introduction of the device was a subjective sense of relief. In any case it was decided to recommend the resting after the introduction of Arabin pessary, even in cases of marked flabby cervix. MATERIALS AND METHODS Our experience is based on the application of 32 Arabin pessary of ASQ type in the period October May In 28/32 cases (p=87.5%) they were singleton pregnancies and in 4/32 cases (p=12.5%) were twins pregnancies (3 bigemine pregnancies and 1 triplets). Only in 3 patients (p=90.6%) was the first pregnancy (1 triplets, 1 twins and 1 singleton pregnancy), while the others were all multiparous. Regardless the number of fetuses, in all pregnancies the pessary has been positioned between the 22nd and 23rd week due to an apparent shortening of the cervix measured with TVS (average length 23 mm); in 3 cases the shortening was an isolated finding (short cervix) while in the remaining cases were associated sonographic signs of flabby cervix (funnelling and hypoechoic stromal). In the remaining singleton pregnancies (28/32 cases, p=87.5%) the device was inserted between the 22nd and 28th weeks on the basis of ultrasound flabby cervix (short cervix, funnelling and hypoechoic stromal); only in 4/28 cases (p=14.3%) was considered discriminating the presence of only short cervix. In 26/32 cases (p=81%) the pessary was removed between 36th and 37th weeks with spontaneous delivery at 38 weeks (7/26 cases, p=27%), at 39th weeks (12/26 cases p=46%) and at 40th weeks or over (7/26 cases, p=27%); in 2/7 patients who delivered spontaneously were twins pregnancies. In remaining 5/32 cases (p=16%) the device was removed at 34 weeks with cesarean delivery for the 36th to 37th weeks in twins pregnancies in previous cesarean sections (2/5 cases, p =40%) or multiple previous cesarean sections in 3/5 cases (p=60%); in 1/32 case (p=3%) the pessary was removed after cesarean section for forgetfulness. In 2/26 cases (p=7,6%) the pessary was not removed despite premature rupture of membranes at 28 and 31 weeks, but until the complete removal at the term (37 and 38 weeks), we performed weekly vaginal swab, blood count and serum PCR to 23

24 It. J. Gynaecol. Obstet. 2015, 27: N.1 24 exclude corionamnionitis onset. In 22/32 pregnant women (p=69%) application of pessary has been associated with the use of (GROUP A): Progesterone (21,22,23,24,34,40), micronized vaginally or orally, 400 mg bid in 18/22 patients (p=82%); Magnesium [24,40], orally 400 mg m.i.d. in 18/22 patients (p=82%); Nifedipine (21,23), orally 20 mg b.i.d. in 4/22 patients (p=18%); Lactoferrine o Lactoglobuline (40,42), vaginally 300 mg m.i.d. in 4/22 patients (p=18%). In 10/32 cases (p=31%) was not associated any medications (GROUP B). So let s see how to insert and remove the Arabin pessary. The Arabin pessary, covered with antibacterial cream on the surface that will contact with fornices, is squeezed between thumb and forefinger with the larger hole facing up and plugged intake vagina with the major axis parallel to the major axis of the vagina. Within the vagina the device opens and with 2 fingers gently pushing towards fornices and place it so that cervix is completely included in the smaller hole. Once obtained the positioning, remains the most important act, or give the right angle to the cervix in order to maintain the cervixuterine angle at a value comprised between 30 and 45 (16,42). To achieve this objective to push with the index finger on the front edge of the rear toward the sacral bone. Immediately after insertion, the patient is asked to walk for a few minutes and to report any unpleasant sensations; the presence of a prolonged and worsening sense of discomfort should make us reconsider the size or type of device placed (9,16,42). Usually the device has been removed around the 37th week, except the onset of contractions or PROM before that period; in our series in 2 cases the pessary was not removed despite premature rupture of membranes at 28 and 31 weeks, but until the complete removal at the term (37 and 38 weeks), we performed weekly vaginal swab, blood count and serum PCR to exclude corionamnionitis onset. Of course the use of the pessary should not be extended to all women with flabby cervix, but there are some conditions that contraindicate the use of the pessary. Should be considered absolute contraindications (9,14,36,42) : presence of major fetal malformations incompatible with life; corionamnionitis known or suspected; protrusion of the amniotic membranes over an external uterine gaping orifice; valid and rhythmic uterine contractions; bleeding of uterine origin; placenta praevia major; previous cervical conization with the remaining cervix of <30%; premature rupture of membranes; gestational age <22 or> 30 weeks. Instead should be considered relative contraindications (9,14,36,42) : marginal or partial placenta praevia; rupture of the membranes with small eccentric outflow of amniotic fluid and no sign of amnionitis; further uterine malformations, such as a uterus bicolle in which the positioning of the pessary may be very problematic; previous cervical conization with residual cervix of 50%; gestational age between 30 and 32 week. RESULTS We ve applicated 32 Arabin pessary of ASQ type in the period October 2012-May In 28/32 cases (p=87.5%) they were singleton pregnancies and in 4/32 cases (p=12.5%) were twins pregnancies (3 bigemine pregnancies and 1 triplets). Only in 3 patients (p=90.6%) was the first pregnancy (1 triplets, 1 twins and 1 singleton pregnancy), while the others were all multiparous. All patients showed flabby cervix or simply short cervix, but all of them have reached the end of pregnancy despite initial expectations. In 26/32 cases (p=81%) the pessary was removed between 36th and 37th weeks with spontaneous delivery at 38 weeks (7/26 cases, p=27%), at 39th weeks (12/26 cases p=46%) and at 40th weeks or over (7/26 cases, p=27%); in 2/7 patients who delivered spontaneously were twins pregnancies. In remaining 5/32 cases (p=16%) the device was removed at 34 weeks with cesarean delivery for the 36th to 37th weeks in twins pregnancies in previous cesarean sections (2/5 cases, p =40%) or multiple previous cesarean sections in 3/5 cases (p=60%); in 1/32 case (p=3%) the pessary was removed after cesarean section for forgetfulness. In 2/26 cases (p=7,6%) the pessary was not removed despite premature rupture of membranes at 28 and 31 weeks, but until the complete removal at the term (37 and 38 weeks), we performed weekly vaginal swab, blood count and serum PCR to exclude corionamnionitis onset.

25 L. Juliano et al. We already said that in 22/32 pregnant women (p=69%) application of pessary has been associated with a medication (GROUP A), while in 10/32 cases (p=31%) was associated anything (GROUP B). Surprisingly, the outcome of these 2 latter groups did not show substantial changes, so as to lead us to believe that the exclusive action of the vaginal device is the real creator of obtained benefits. Last notation should be made on the weight of pregnant women at insertion; the majority of pregnant women showed when inserting a BMI> 25 (n =30, p =94%) while only 2 were 25, which account for the increased risk of preterm delivery in pregnant women are overweight. All the foregoing is however a speech in constant evolution; thus, for example, as squeezing and angling the cervix prevents the mobilization of the cervical mucus, whose key role in the stabilization of collagen tissue and extracellular matrix by the hydration of the fibers is still today under study, both through the new techniques of PCR molecular biology both by promising transvaginal sonoelastography. DISCUSSION While as claimed by anglosaxon authors to do nothing is not an option any longer [42], the American College of Obstetricians and Gynecologists (ACOG) underlines the risk of unnecessary interventions in single pregnancies without a history of childbirth spontaneous preterm. In one of the most important study published by Goya in Lancet on 2012 (14), a multicenter study on the use of the pessary in women with short cervical length selected (<25mm) aged between 18 and 22 weeks showed that the use of the pessary increases the pregnancy rate come to term with respect to control. In this study, 385 women were recruited: 192 was placed an Arabin pessary, while 193 were adopted alternative therapeutic measures. Were excluded women with a higher fetal malformation, those with actual uterine contractions, vaginal bleeding, and premature rupture of membranes, placenta previa, or a history of conization or cerclage in situ. In the group with pessary has had the lowest rate of births before 34 weeks (6% vs27%), before the 37th week (22% vs 59%) and before the 28th week (2% vs 8%). Of course the use of the pessary should not be extended to all women with flabby cervix, but there are some conditions that contraindicate the use of the pessary, conditions, as already mentioned, unanimously shared by the various authors consulted in indexed publications. As mentioned in our experience the sensation reported by all patients at approximately 30 minutes from the introduction of the Arabin pessary has been enjoyable and a subjective sense of relief. The Arabin pessary is officially indicated in all cases of preterm delivery threatened, certified registered with the Ministries of Health in all countries of the European Union (Identification number: MED/ CERT0482 EN ISO13485 Council directive 93/42/EEC reg. medical devices), in Scandinavia, the Russian Federation, Indonesia and the United Arab Emirates (9,14,36,42). It s necessary to confirm the correct positioning of the pessary after insertion through a clinical and sonographic examination. In all cases of expulsion of device, operator independent, the pessary can be repositioned; a further expulsion should lead one to consider a change of measure or type of pessary. In general, the pessary should be kept in place for up to 37 weeks if there are no indications for early removal. The patient will be asked to notify the obstetrician in case of discomfort, contractions or vaginal bleeding. The pessary should always be considered a foreign body in the vagina, so it is important to carefully observe periodic prophylactic hygienic washes and ovules antiseptic of chlorhexidine. As regards the combination of tocolitic and/ or colpotonic therapies, has already been said that in our report 69% of cases has been associated with use of progesterone, magnesium, nifedipine and lactoferrin, while in 31% of cases was not associated with any medications. In case of hospitalization prior to the planned removal of the pessary, you should always inform the staff of the structure in order to allow the inevitable premature removal if deemed necessary (9,14,36,42). All the foregoing is however a speech in constant evolution; new techniques of PCR molecular biology and promising transvaginal sonoelastography will certainly contribute to the development and refinement of new knowledges for the prevention of preterm birth. 25

26 It. J. Gynaecol. Obstet. 2015, 27: N.1 26 REFERENCES 1) GoldenbergRL, Gravett MG, Iams J, Papageorghiou AT, Waller SA, Kramer M, Culhane J, Barros F, Conde- Agudelo A, Bhutta ZA, Knight HE, Villar J. The preterm birth syndrome: issues to consider in creating a classification system. Am J Obstet Gynecol 2012; 206: ) Romero R, Mazor M, Munoz H, Gomez R, Galasso M, Sherer DM. The preterm labor syndrome. Ann N Y Acad Sci 1994; 734: ) Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, Rudan I, Campbell H, Cibulskis R, Li M, Mathers C, Black RE. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since Lancet 2012; 379: ) Culligan PJ. Nonsurgical management of pelvic organ prolapse. Obstet Gynecol 2012; 119: ) Cross R. Treatment of habitual abortion due to cervical incompetence. Lancet 1959; 274: ) Oster S, Javert CT. Treatment of the incompetent cervix with the Hodge pessary. Obstet Gynecol 1966; 28: ) Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA. Cervical pessary for preventing preterm birth. Cochrane Database Syst Rev 2010; 9: CD ) Arabin H. Pessartherapie (Therapy with pessaries). In Gynakologie, Martius G (ed). Thieme: Stuttgart-New York, 1991, ) Arabin B, Halbesma JR, Vork F, Hubener M, van Eyck J. Is treatment with vaginal pessaries an option in patients with a sonographically detected short cervix? J Perinat Med2003; 31: ) Goya M, Pratcorona L, Higueras T, Perez-Hoyos S, Carreras E, Cabero L. Sonographic cervical length measurement in pregnant women with a cervical pessary. Ultrasound Obstet Gynecol 2011; 38: ) Sieroszewski P, Jasinski A, Perenc M, Banach R, Oszukowski P. The Arabin pessary for the treatment of threatened mid- trimester miscarriage or premature labour and miscarriage: a case series. J Matern Fetal Neonatal Med 2009; 22: ) Kimber-Trojnar Z, Patro-Malysza J, Leszczynska- Gorzelak B, Marciniak B, Oleszczuk J. Pessary use for the treatment of cervical incompetence and prevention of preterm labour. J Matern Fetal Neonatal Med 2010; 23: ) Ting YH, Lao TT, Law LW, Hui SY, Chor CM, Lau TK, Leung TY. Arabin cerclage pessary in the management of cervical insufficiency. J Matern Fetal Neonatal Med 2012; 25: ) Goya M, Pratcorona L, Merced C, Rodo C, ValleL, Romero A, Juan M, Rodriguez A, Munoz B, Santacruz B, Bello-Munoz JC, Llurba E, Higueras T, Cabero L, Carreras E. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet 2012; 379: ) Cannie MM, Dobrescu O, Gucciardo L, Strizek B, Ziane S, Sakkas E, Schoonjans F, Divano L, Jani JC. Arabin cervical pessary in women at high risk of preterm birth: a magnetic resonance imaging observational follow-up study. Ultrasound Obstet Gynecol 2013; 42: ) Arabin B, Roos C, Kollen B, van Eyck J. Comparison of transvaginal sonography in recumbent and standing maternal positions to predict spontaneous preterm birth in singleton and twin pregnancies. Ultrasound Obstet Gynecol 2006; 27: ) Romero R, Friel LA, Velez Edwards DR, Kusanovic JP, Hassan SS, Mazaki-Tovi S, Vaisbuch E, Kim CJ, Erez O, Chaiworapongsa T, Pearce BD, Bartlett J, Salisbury BA, Anant MK, Vovis GF, Lee MS, Gomez R, Behnke E, Oyarzun E, Tromp G, Williams SM, Menon R. A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM). Am J Obstet Gynecol 2010; 203: 361, ) Becher N, Adams Waldorf K, Hein M, Uldbjerg N. The cervical mucus plug: structured review of the literature. Acta Obstet Gynecol Scand 2009; 88: ) Lee DC, Hassan SS, Romero R, Tarca AL, Bhatti G, Gervasi MT, Caruso JA, Stemmer PM, Kim CJ, Hansen LK, Becher N, Uldbjerg N. Protein profiling underscores immunological functions of uterine cervical mucus plug in human pregnancy. J Proteomics 2011; 74: ) Liem SM, van Pampus MG, Mol BW, Bekedam DJ. Cervical pessaries for the prevention of preterm birth: a systematic review. Obstet Gynecol Int 2013; 2013: ) Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med2007; 357: ) Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, mbareyp,dayala,potapovv,o BrienJ,AstakhovV,Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde- Agudelo A, Phillips JA, Creasy GW. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2011; 38: ) Romero R, Nicolaides KH, Conde-AgudeloA, TaborA, O Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Klein K, Rode L, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol 2012; 206: 124, ) Campbell S. Universal cervical-length screening and vaginal progesterone prevents early preterm births, reduces neonatal morbidity and is cost saving: doing nothing is no longer an option. Ultrasound Obstet Gynecol 2011; 38: ) Practice bulletin no. 130: prediction and prevention of preterm birth. Obstet Gynecol 2012; 120: ) Berghella V, Baxter JHK, Hendrix NW. Cervical

27 L. Juliano et al. assessment by ultrasound for preventing preterm delivery. CochraneDatabase Syst Rev 2013; 1: CD ) Nicolaides KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol 2004; 191: ) Hui SY, Chor CM, Lau TK, Lao TT, Leung TY. Cerclage pessary for preventing preterm birth in women with a singleton pregnancy and a short cervix at 20 to 24weeks: a randomized controlled trial. Am J Perinatol 2013; 30: ) HonestH, BachmannLM, CoomarasamyA, GuptaJK, Kleijnen J, Khan KS. Accuracy of cervical transvaginal sonography in predicting preterm birth: a systematic review. Ultrasound Obstet Gynecol 2003; 22: ) Salomon LJ, Diaz-Garcia C, Bernard JP, Ville Y. Reference range for cervical length throughout pregnancy: non-parametric LMS-based model applied to a large sample.ultrasoundobstet Gynecol 2009; 33: ) Alfirevic Z, Owen J, Carreras Moratonas E, Sharp AN, Szychowski JM, Goya M. Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnant women with history of preterm birth and a sonographic short cervix. Ultrasound Obstet Gynecol 2013; 41: ) Makrydimas G. Re: Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnant women with history of preterm birth and a sonographic short cervix. Ultrasound Obstet Gynecol 2013; 41: ) Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM. Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient- level data. Obstet Gynecol 2005; 106: ) Rode L, Klein K, Nicolaides KH, Krampl-Bettelheim E, Tabor A. Prevention of preterm delivery in twingestations (PREDICT): a multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone. Ultrasound Obstet Gynecol 2011; 38: ) Lee SM, Jun JK. Prediction and prevention of preterm birth after cervical conization. J Gynecol Oncol 2010; 21: ) Society of Maternal Fetal Medicine assisted by Vinceco Berghella. Progesterone and preterm birth prevention: trans- lating clinical trials data into clinical practice. Am J Obstet Gynecol 2012; 206: ) Feltovich H, Hall TJ. Quantitative imaging of the cervix: setting the bar. Ultrasound Obstet Gynecol 2013; 41: Romero R, Mazaki-Tovi S, Vaisbuch E, Kusanovic JP, Chaiworapongsa T, Gomez R, Nien JK, Yoon BH, Mazor M, LuoJ,BanksD, RyalsJ, Beecher C. Metabolomics in premature labor: a novel approach to identify patients at risk for preterm delivery. J Matern Fetal Neonatal Med 2010; 23: ) Burwick RM, Lee GT, Benedict JL, Ross MG, Kjos SL. Blinded comparison of cervical portio length measurements by digital examination vs Cervilenz. Am J Obstet Gynecol 2009; 200: e ) Conde-Agudelo A, Romero R, Nicolaides KH, Chaiworapongsa T, O Brien JM, Cetingoz E, da Fonseca E, Creasy G, Soma- Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis. Am J Obstet Gynecol 2013; 208: 42, ) Ferguson JKW. A study of the motility of the intact uterus at term. Surg. Gynecol Obstet. 1941; 73: ) Arabin B, Alfirevic. Cervical Pessaries for prevention of spontaneous preterm birth: past, present and future. Ultrasound Obstet Gynecol. 2013; 42: ) Locci M, Nazzaro G, Miranda M, Salzano E, Montagnani S, Castaldo C, De Placido G. Vaginal lactoferrin in asymptomatic patients at low risk for pre-term labour for shortened cervix: cervical length and interleukin-6 changes. J Obstet Gynaecol Feb;33(2):

28 Serum C-reactive protein as potential independent prognostic factor for breast cancer Adela Stoenescu* 2, Christoph Gerlinger 1, Erich Franz Solomayer 1, Christoph Scholz 2, Ingolf Juhasz-Böss 1, Julia Radosa 1 1 Department of Obstetrics and Gynaecology, University of Saarland, Homburg / Saar, Germany 2 Department of Obstetrics and Gynaecology, University of Ulm, Ulm, Germany ABSTRACT BACKGROUND: The possible involvement of inflammation in breast carcinogenesis has potential prognostic and therapeutic consequences. We investigated whether C-reactive protein is expressed in breast cancer and evaluated its correlation with clinicopathological findings. METHODS: We analyzed CRP in plasma samples of 219 cases of metastatic and nonmetastatic invasive cancer and carcinoma in situ, selected among participants in a retrospective study. Circulating plasma CRP measurements were performed at the time of primary diagnosis. RESULTS: We observed higher levels of CRP in patients with cancer compared with patients with non-invasive tumors (p=0.0037) and a significant association between elevated CRP levels and advanced tumor stage only in patients with nonmetastatic breast cancer. The CRP level significantly increases with the size of the breast cancer in patients with non-metastatic disease: Tis 1.58 mg/l, T mg/l, T mg/l, T mg/l, T mg/l; p= CONCLUSION: Our data suggest that elevated plasma CRP levels are associated with advanced stages of breast cancer and bad prognosis. CRP levels might be an independent and potential long-term prognostic factor for breast cancer and could be probable used as tumor marker in patients without inflammatory diseases. Non-steroidal anti-inflammatory drugs could be used in the treatment of malignancy. Several trials are being conducted to study the use of COX (enzyme cyclo-oxygenase) inhibitors in the treatment of breast cancer. Keywords: Breast cancer, prognosis, inflammation, tumor maker. SOMMARIO BACKGROUND: Il possibile coinvolgimento dell infiammazione nella carcinogenesi ha un potenziale prognostico e delle conseguenze terapeutiche. Abbiamo investigato sull eventualità che la proteina C-reattiva sia coinvolta nel cancro al seno e abbiamo valutato la sua correlazione con i riscontri clinicopatologici. METODOLOGIA: abbiamo analizzato il CRP nei campioni di sangue di 219 casi di cancro invasivo metastatico e non, e nel carcinoma in situ, selezionati tra I partecipanti agli studi retrospettivi. I valori di CRP nel plasma sono stati misurati al momento della diagnosi primaria. RISULTATI: Abbiamo osservato un maggiore livello di CRP in pazienti con il cancro rispetto a pazienti con tumori non invasivi (p = ) e una significativa correlazione tra i livelli di CRP elevati e il tumore in uno stadio avanzato presente nei pazienti con cancro al seno non metastatico. Il livello di CRP aumenta significatamente con l ingrandirsi del cancro al seno non metastatico: Tis 1.58 mg/l, T mg/l, T mg/l, T mg/l, T mg/l; p= CONCLUSIONI: I nostri dati suggeriscono che elevati livelli di CRP nel sangue sono associabili con stadi avanzati di cancro al seno e prognosi maligne. I livelli di CRP potrebbero essere un potenziale fattore di prognosi a lungo termine del cancro al seno e probabilmente potrebbe venir usato come marcatore tumorale nei pazienti senza malattie infiammatorie. Farmaci anti-infiammatori non steroidei possono essere usati nel trattamento delle neoplasie maligne. Sono stati condotti numerosi trials sullo studio dell utilizzo dei COX (enzima ciclo-ossignasi) inibitori nel trattamento del cancro al seno. INTRODUCTION Chronic inflammation has been hypothesized for many years to be associated with cancer development and progression and has been studied for a long time (1-3). Serum C-reactive protein (CRP), an acute phase protein and a sensitive nonspecific marker of systemic inflammation, has been reported to be associated with a number of cancers, including breast cancer. Its expression is induced by proinflammatory cytokines and is produced mainly in hepatocytes (17). However, results in the literature Correspondence to: Copyright 2014, Partner-Graf srl, Prato are inconsistent and remain controversial. There are two hypotheses that might explain the correlation between CRP and cancer: 1) high CRP levels are a result of cancer or a premalignant state; 2) chronic inflammation with elevated CRP concentrations promotes cancer growth (6). The production of cytokines and growth factors, the induction of cyclooxygenase-2 in macrophages and epithelial cells, the generation of mutagenic reactive oxygen, and nitrogen species are possible mechanisms for carcinogenesis (18). Cytokines (interleukin-1, interleukin-6, tumour necrosis factor) regulate the synthesis of CRP. The role of elevated CRP levels in patients with carcinoma is not yet clear. Nozoe et al. first described an association between CRP and carcinogenesis in patients with oesophageal 28

29 A. Stoenescu et al. squamous carcinoma (19). They demonstrated an increased incidence of peritoneal, lymph node and liver metastases, intravascular invasion and poor prognosis in patients with preoperatively increased CRP levels. It has been reported that serum CRP expression has a prognostic value for gastric, colorectal, esophageal carcinoma, multiple myeloma and malignant fibrous histiocytoma (19-23). It has not been clarified, however, whether the serum CRP expression is a prognostic indicator in patients with breast cancer. Some previous studies have reported that breast cancer patients have elevated levels of CRP before surgery, especially in women with advanced disease (16). The results showed that the higher the CRP level at diagnosis, the worse the prognosis was. Elevated levels have been associated with poor prognosis in patients with breast cancer (6,12). Therefore, the aim of our retrospective study was to investigate the association between serum CRP levels before treatment and the pathological stages of breast cancer. PATIENTS AND METHODS We analyzed CRP in plasma samples of 532 cases of invasive cancer and 49 cases of carcinoma in situ, selected among participants in a retrospective study. The study population included participants who were diagnosed and treated at the Department of Gynaecology at the Saarland University Hospital between January 2010 and December Patients with documented bacterial infections and high CRP levels were excluded from the study. Information concerning age, menopausal status, diagnosis, and clinical pathology were collected for each patient and are summarized in Table I. The breast cancer patients were staged according to TNM-UICC classification. 532 patients were diagnosed histologically with ductal infiltrating carcinoma, along with 49 of carcinoma in situ. Tumor size was classified as T1 (less than or equal to 2 cm) in 297 (50.77 %), T2 (tumor size between 2 and 5 cm) in 157 (26.84 %), T3 (tumor size more than 5 cm) in 27 (4.62 %) and T4 (tumor extends to chest wall) in 29 (4.96 %) of the cases. Table I: Main clinical-pathological tumor characteristics of 586 breast cancer patients Characteristic Patients Percent Characteristic Patients Percent Age < 50 years years > 70 years % % % Menopausal status Premenopausal Perimenopausal Postmenopausal % 5.97 % % Histological diagnosis Grading Infiltrating carcinoma In situ carcinoma % 8.43 % G1 G2 G % % % Tumor size Nodal involvement T % N % T % N % T % N % T % N % Metastatic site HER2/neu status M % Negative % M % Positive % ER status % PgR status Negative % Negative % Positive Positive % Local relapse Death No % No % Yes % Yes % 29

30 It. J. Gynaecol. Obstet. 2015, 27: N.1 There were 400 patients with negative lymph nodes and 162 patients with positive lymph nodes. Main tumor characteristics are shown in Table I. Circulating plasma CRP measurements were performed at the time of primary diagnosis in 219 participants. The cut-off level for serum CRP was established at 5 mg/l. We determined the plasma CRP levels in fresh plasma samples in our laboratories at the Department of Clinical Biochemistry, Saarland University Hospital. The statistical analyses were carried out using SAS version 9.2 statistics software. The Kruskal-Wallis test was used for relating CRP levels to clinicopathological parameters. A p-value of less than 0.05 was considered to be significant. Serum levels of CRP in patients with nonmetastatic and low-grade malignancy cancers (G1) did not differ significantly as compared with patients with medium (G2), respectively high-grade malignancy cancers (G3): 2.84 mg/l vs mg/l, respectively 4.84 mg/l, p>>0.05 (Figure 2). RESULTS High circulating plasma levels (> 5 mg/l) of CRP were associated with advanced-stage breast cancer and metastasis. Of the 219 patients with data, 43 (19.63%) showed an abnormal CRP level at the time of primary diagnosis. Patients diagnosed with invasive cancers had significantly higher levels of CRP than patients with carcinoma in situ; p= A mean CRP concentration of 5.91 mg/l was found, while patients with noninvasive cancers had a mean CRP level of 1.25 mg/l. Relationship between CRP and tumor characteristics in adjuvant patients We noted that CRP levels did differ significantly with tumor size. The CRP level significantly increases with the size of the breast cancer in patients with nonmetastatic disease: Tis 1.58 mg/l, T mg/l, T mg/l, T mg/l, T mg/l; p= (Figure 1). Figure 2: CRP and grading We evaluated correlation of CRP level at the time of primary diagnosis with nodal burden. CRP concentrations were higher in patients with positive nodal status. Patients with no lymph node involvement (N0) had a mean CRP level of 4.07 mg/l, while patients with positive axillary lymph nodes as follows: N mg/l, N mg/l. There was only one patient with N3 breast cancer, who had a CRP level at the time of primary diagnosis of 1.80 mg/l. However, the observed differences of CRP levels are not significant (Figure 3). Figure 3: CRP and nodal status 30 Figure 1: CRP and tumor stage Relationship between CRP and tumor characteristics in patients with metastatic disease 26 patients with data had distant metastasis at time of their initial breast cancer diagnosis as follows: 5 patients had lung metastases, 8 bone metastases, 2 liver metastases and the others had more than one

31 A. Stoenescu et al. location of distant metastasis. Patients with metastatic disease had a mean CRP level of 3.43 mg/l, almost equal to patients with non-metastatic disease (Figure 4). Figure 6: CRP and nodal status Figure 4: Relationship between CRP and distant metastases in patients with non-metastatic vs. metastatic disease Non-significant elevations of CRP levels were observed in patients with T2, respectively T4 breast cancer and distant metastases (4.44 mg/l, respectively 4.10 mg/l). A CRP level of 3.70 mg/l was observed in patients with T1 breast cancer. There was only one patient with T3 breast cancer and distant metastases with a CRP level of 1.40 mg/l (Figure 5). Figure 7: CRP and grading Figure 5: CRP and tumor stage CRP serum levels increase with nodal status of breast cancer. This difference again did not reach statistical significance. A level of 3.15 mg/l was observed in nodal negative patients. Patients with N1 and N2 breast cancer had a CRP level of 3.85 mg/l and 3.80 mg/l, respectively, while a level of 4.00 mg/l was observed in patients with N3 breast cancer (Figure 6). The CRP concentrations were independent of grading in patients with distant metastases (Figure 7). Correlation of CRP level at the time of primary diagnosis with ER, PgR and HER2-expressions We didn t notice any significant correlations of CRP levels with receptor status in our study. A detailed breakdown of distribution is shown in Figures No difference was observed in patients with nonmetastatic compared to metastatic hormone receptor positive, HER2-negative breast cancer (Figure 8). Patients with metastatic hormone receptor positive, HER2-positive breast cancer had non-significant lower CRP levels than patients with non-metastatic disease, 2.75 mg/l compared to 4.37 mg/l (Figure 9). Slightly higher CRP levels were observed in patients with non-metastatic triple negative breast cancer (3.52 mg/l) compared to patients with metastatic triple negative breast cancer (2.30 mg/l) (Figure 11). Similarly, patients with non-metastatic hormone receptor negative, HER2-positive disease had a non-significant higher CRP level than patients with metastases, 7.72 mg/l vs mg/l (Figure 10). 31

Quali indicazioni nelle donne con BRCA sane, mutate

Quali indicazioni nelle donne con BRCA sane, mutate Negrar, 13 0ttobre Quali indicazioni nelle donne con BRCA sane, mutate Annamaria Molino, oncologa Di cosa stiamo parlando Mastectomia bilaterale e ovariectomia profilattiche Nonna ca mammella Rischio cumulativo

Dettagli

IL NODULO ALLA MAMMELLA

IL NODULO ALLA MAMMELLA IL NODULO ALLA MAMMELLA SCUOLA REGIONALE DI FORMAZIONE SPECIFICA IN MEDICINA GENERALE 18.04.2012 Giancarlo Bisagni Dipartimento di Oncologia SERVIZIO SANITARIO REGIONALE EMILIA-ROMAGNA AZIENDA OSPEDALIERA

Dettagli

MALATTIA TROMBOEMBOLICA VENOSA 2014 : NUOVI FARMACI = NUOVI PERCORSI? Rino Migliacci

MALATTIA TROMBOEMBOLICA VENOSA 2014 : NUOVI FARMACI = NUOVI PERCORSI? Rino Migliacci MALATTIA TROMBOEMBOLICA VENOSA 2014 : NUOVI FARMACI = NUOVI PERCORSI? Rino Migliacci Choice of Initial Anticoagulant Regimen in Patients With Proximal DVT In patients with acute DVT of the leg, we

Dettagli

REGISTRATION GUIDE TO RESHELL SOFTWARE

REGISTRATION GUIDE TO RESHELL SOFTWARE REGISTRATION GUIDE TO RESHELL SOFTWARE INDEX: 1. GENERAL INFORMATION 2. REGISTRATION GUIDE 1. GENERAL INFORMATION This guide contains the correct procedure for entering the software page http://software.roenest.com/

Dettagli

ISAC. Company Profile

ISAC. Company Profile ISAC Company Profile ISAC, all that technology can do. L azienda ISAC nasce nel 1994, quando professionisti con una grande esperienza nel settore si uniscono, e creano un team di lavoro con l obiettivo

Dettagli

La malattia oligometastatica: clinica o biologia nella strategia terapeutica?

La malattia oligometastatica: clinica o biologia nella strategia terapeutica? La malattia oligometastatica: clinica o biologia nella strategia terapeutica? Lucia Del Mastro SS Sviluppo Terapie Innovative Bergamo 6 luglio 2014 IRCCS Azienda Ospedaliera Universitaria San Martino IST

Dettagli

ELCART. Manuale di istruzioni/scheda tecnica SPECIFICATION

ELCART. Manuale di istruzioni/scheda tecnica SPECIFICATION PAGINA 1 DI 7 SPECIFICATION Customer : ELCART Applied To : Product Name : Piezo Buzzer Model Name : : Compliance with ROHS PAGINA 2 DI 7 2/7 CONTENTS 1. Scope 2. General 3. Maximum Rating 4. Electrical

Dettagli

Sezione 1 / Section 1. Elementi d identità: il marchio Elements of identity: the logo

Sezione 1 / Section 1. Elementi d identità: il marchio Elements of identity: the logo Sezione 1 / Section 1 2 Elementi d identità: il marchio Elements of identity: the logo Elements of identity: the logo Indice 2.01 Elementi d identità 2.02 Versioni declinabili 2.03 Versioni A e A1, a colori

Dettagli

Sessione IV Ricerca e sviluppo per i programmi di screening

Sessione IV Ricerca e sviluppo per i programmi di screening Sessione IV Ricerca e sviluppo per i programmi di screening o L Adeguamento delle linee-guida dello screening del cervicocarcinoma o I Vaccini anti-hpv e gli Screening o Modelli di interazione tra screening

Dettagli

La terapia farmacologica

La terapia farmacologica La terapia farmacologica Angelo Bianchetti Gruppo di Ricerca Geriatrica, Brescia Dipartimento Medicina e Riabilitazione, Istituto Clinico S.Anna, Brescia Gli outcome del trattamento del delirum Prevenzione

Dettagli

La terapia non chirurgica!

La terapia non chirurgica! La gestione dell incontinenza urinaria da sforzo, costi sociali e qualità di vita!! La terapia non chirurgica!! GF. Lamberti!! Commissione Riabilitazione SIUD!! ambulatorio riabilitazione perineale! ASL

Dettagli

Copyright 2012 Binary System srl 29122 Piacenza ITALIA Via Coppalati, 6 P.IVA 01614510335 - info@binarysystem.eu http://www.binarysystem.

Copyright 2012 Binary System srl 29122 Piacenza ITALIA Via Coppalati, 6 P.IVA 01614510335 - info@binarysystem.eu http://www.binarysystem. CRWM CRWM (Web Content Relationship Management) has the main features for managing customer relationships from the first contact to after sales. The main functions of the application include: managing

Dettagli

Innovazioni terapeutiche in Oncologia Medica Cagliari 23/24 Giugno 2005

Innovazioni terapeutiche in Oncologia Medica Cagliari 23/24 Giugno 2005 Innovazioni terapeutiche in Oncologia Medica Cagliari 23/24 Giugno 2005 Associazione Trastuzumab e chemioterapia nel carcinoma mammario metastatico e localmente avanzato. Nostra casistica. Carlo Floris

Dettagli

On Line Press Agency - Price List 2014

On Line Press Agency - Price List 2014 On Line Press Agency - Price List Partnerships with Il Sole 24 Ore Guida Viaggi, under the brand GVBusiness, is the official publishing contents supplier of Il Sole 24 Ore - Viaggi 24 web edition, more

Dettagli

Sponsorship opportunities

Sponsorship opportunities The success of the previous two European Workshops on Focused Ultrasound Therapy, has led us to organize a third conference which will take place in London, October 15-16, 2015. The congress will take

Dettagli

Alfredo Berruti Università degli Studi di Brescia Azienda Ospedaliera Spedali Civili Brescia

Alfredo Berruti Università degli Studi di Brescia Azienda Ospedaliera Spedali Civili Brescia HOT TOPICS MALATTIA METASTATICA Malattia Ormonosensibile Alfredo Berruti Università degli Studi di Brescia Azienda Ospedaliera Spedali Civili Brescia MALATTIA METASTATICA ORMONOSENSIBILE Nel paziente in

Dettagli

SCREENING PER LA PREVENZIONE DEL TUMORE DELLA MAMMELLA

SCREENING PER LA PREVENZIONE DEL TUMORE DELLA MAMMELLA SCREENING PER LA PREVENZIONE DEL TUMORE DELLA MAMMELLA Controversie sullo screening mammografico: pro e contro Edda Simoncini Breast Unit A.O.Spedali Civili Brescia Spedali Civili di Brescia Azienda Ospedaliera

Dettagli

GLI ANDAMENTI TEMPORALI DELLA PATOLOGIA ONCOLOGICA IN ITALIA

GLI ANDAMENTI TEMPORALI DELLA PATOLOGIA ONCOLOGICA IN ITALIA e&p GLI ANDAMENTI TEMPORALI DELLA PATOLOGIA ONCOLOGICA IN ITALIA Linfomi: linfomi di Hodgkin e linfomi non Hodgkin Lymphomas: Hodgkin and non-hodgkin Lymphomas Massimo Federico, 1 Ettore M. S. Conti (

Dettagli

ATTESTATO DELL ATTIVITÀ DI VOLONTARIATO CERTIFICATE OF VOLUNTARY ACTIVITIES

ATTESTATO DELL ATTIVITÀ DI VOLONTARIATO CERTIFICATE OF VOLUNTARY ACTIVITIES ASSOCIAZIONE CONSORTI DIPENDENTI MINISTERO AFFARI ESTERI ATTESTATO DELL ATTIVITÀ DI VOLONTARIATO CERTIFICATE OF VOLUNTARY ACTIVITIES ASSOCIAZIONE CONSORT I DIPENDENTI MINISTE RO AFFARI ESTER I ATTESTATO

Dettagli

La vaccinazione HPV: dalla prevenzione primaria alla riduzione delle recidive G. Baitelli G. Tisi (AO Spedali Civili BS)

La vaccinazione HPV: dalla prevenzione primaria alla riduzione delle recidive G. Baitelli G. Tisi (AO Spedali Civili BS) La vaccinazione HPV: dalla prevenzione primaria alla riduzione delle recidive G. Baitelli G. Tisi (AO Spedali Civili BS) In Italia, ogni anno, si stimano 14.700 casi di CIN 2/3 e 47.000 CIN1 È INDICATO:

Dettagli

I COSTI RAPPRESENTANO UN PROBLEMA IN CHIRURGIA LAPAROSCOPICA?

I COSTI RAPPRESENTANO UN PROBLEMA IN CHIRURGIA LAPAROSCOPICA? I COSTI RAPPRESENTANO UN PROBLEMA IN CHIRURGIA LAPAROSCOPICA? M.M. Lirici SESSIONE SIC-SICE Sistema ABC ACTIVITY BASED COSTING Gli elementi che generano il costo sono quelli che richiedono una prestazione

Dettagli

Le cellule staminali dell embrione: cosa possono fare Embryonic stem cells are exciting because they can make all the different types of cell in the

Le cellule staminali dell embrione: cosa possono fare Embryonic stem cells are exciting because they can make all the different types of cell in the 1 2 3 Le cellule staminali dell embrione: cosa possono fare Embryonic stem cells are exciting because they can make all the different types of cell in the body scientists say these cells are pluripotent.

Dettagli

Bruno Meduri. Radioterapia Oncologica - A.O.U. Policlinico di Modena. Associazione Italiana di Radioterapia Oncologica

Bruno Meduri. Radioterapia Oncologica - A.O.U. Policlinico di Modena. Associazione Italiana di Radioterapia Oncologica Bruno Meduri Radioterapia Oncologica - A.O.U. Policlinico di Modena Associazione Italiana di Radioterapia Oncologica Follow up condiviso Il follow-up attivo della donna trattata è parte integrante del

Dettagli

NORME E GUIDE TECNICHE PROGRAMMA DI LAVORO PER INCHIESTE PRELIMINARI TECHNICAL STANDARDS AND GUIDES PROGRAMME OF WORKS FOR PRELIMINAR ENQUIRY

NORME E GUIDE TECNICHE PROGRAMMA DI LAVORO PER INCHIESTE PRELIMINARI TECHNICAL STANDARDS AND GUIDES PROGRAMME OF WORKS FOR PRELIMINAR ENQUIRY NORME E GUIDE TECNICHE PROGRAMMA DI LAVORO PER INCHIESTE PRELIMINARI TECHNICAL STANDARDS AND GUIDES PROGRAMME OF WORKS FOR PRELIMINAR ENQUIRY Il presente documento viene diffuso attraverso il sito del

Dettagli

Misure fisiche di accettazione e prospettive d impiego di un sistema MRgFUS

Misure fisiche di accettazione e prospettive d impiego di un sistema MRgFUS Misure fisiche di accettazione e prospettive d impiego di un sistema MRgFUS A.Torresin, P.Colombo, A.Moscato SC di Fisica Sanitaria Azienda Ospedaliera, alberto.torresin@unimi.it Terminology HIFU (High

Dettagli

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org) 1. Siena X-linking. Siena 2 Febbraio 2007

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org) 1. Siena X-linking. Siena 2 Febbraio 2007 1 Siena X-linking Siena 2 Febbraio 2007 Andrea Paolini Comitato Etico per la sperimantazione clinica dei medicinali Azienda Ospedaliera Universitaria Senese 0577 233204 c_etico@unisi.it Fondazione Toscana

Dettagli

Quality Certificates

Quality Certificates Quality Certificates Le più importanti certificazioni aziendali, di processo e di prodotto, a testimonianza del nostro costante impegno ed elevato livello di competenze. Qualità * certificata * Certified

Dettagli

Stefano Goldwurm Medical geneticist Centro Parkinson - Parkinson Institute Istituti Clinici di Perfezionamento-Milan neurodegenerative diseases,

Stefano Goldwurm Medical geneticist Centro Parkinson - Parkinson Institute Istituti Clinici di Perfezionamento-Milan neurodegenerative diseases, Stefano Goldwurm Medical geneticist Centro Parkinson - Parkinson Institute Istituti Clinici di Perfezionamento-Milan neurodegenerative diseases, movement disorders, Parkinson disease 1- genetic counselling

Dettagli

Combinazioni serie IL-MIL + MOT

Combinazioni serie IL-MIL + MOT Combinazioni tra riduttori serie IL-MIL e MOT Combined series IL-MIL + MOT reduction units Combinazioni serie IL-MIL + MOT Sono disponibili varie combinazioni tra riduttori a vite senza fine con limitatore

Dettagli

UNIVERSITÀ DEGLI STUDI DI TORINO. Instructions to apply for exams ONLINE Version 01 updated on 17/11/2014

UNIVERSITÀ DEGLI STUDI DI TORINO. Instructions to apply for exams ONLINE Version 01 updated on 17/11/2014 Instructions to apply for exams ONLINE Version 01 updated on 17/11/2014 Didactic offer Incoming students 2014/2015 can take exams of courses scheduled in the a.y. 2014/2015 and offered by the Department

Dettagli

Corsi di Laurea Magistrale/ Master Degree Programs

Corsi di Laurea Magistrale/ Master Degree Programs Corsi di Laurea Magistrale/ Master Degree Programs Studenti iscritti al I anno (immatricolati nell a.a. 2014-2015 / Students enrolled A. Y. 2014-2015) Piano di studi 17-27 Novembre 2014 (tramite web self-service)

Dettagli

Appropriatezza nella prescrizione di esami di diagnostica per immagini. 19 settembre 2013 IL PUNTO DI VISTA DELLO SPECIALISTA OSPEDALIERO

Appropriatezza nella prescrizione di esami di diagnostica per immagini. 19 settembre 2013 IL PUNTO DI VISTA DELLO SPECIALISTA OSPEDALIERO Appropriatezza nella prescrizione di esami di diagnostica per immagini 19 settembre 2013 IL PUNTO DI VISTA DELLO SPECIALISTA OSPEDALIERO S.C Oncologia Medica DIPO XVI - Lecco Appropriatezza Appropriato:

Dettagli

WELCOME. Go to the link of the official University of Palermo web site www.unipa.it; Click on the box on the right side Login unico

WELCOME. Go to the link of the official University of Palermo web site www.unipa.it; Click on the box on the right side Login unico WELCOME This is a Step by Step Guide that will help you to register as an Exchange for study student to the University of Palermo. Please, read carefully this guide and prepare all required data and documents.

Dettagli

New, Classic & Old, History, Concept car, Meeting Day, Lifestyle, for fans and members in the world

New, Classic & Old, History, Concept car, Meeting Day, Lifestyle, for fans and members in the world MercedesRoadster.IT New, Classic & Old, History, Concept car, Meeting Day, Lifestyle, for fans and members in the world Newspaper supplement Emmegi Magazine Independent unaffiliated / funded by Daimler

Dettagli

La chirurgia: come, quando e quale

La chirurgia: come, quando e quale La chirurgia: come, quando e quale V. Ziparo Facoltà di Medicina e Psicologia Dipartimento Medico-Chirurgico e Medicina Translazionale Azienda Ospedaliera Sant Andrea Epidemiologia dell Adenocarcinoma

Dettagli

Corneal Cross-Linking Indications

Corneal Cross-Linking Indications Corneal Cross-Linking Indications Aldo Caporossi MD, FRCS Cosimo Mazzotta MD, PhD Stefano Baiocchi MD, PhD Department of Ophthalmology and Neurosurgery Siena University Head: Prof. Aldo Caporossi First

Dettagli

ISO 9001:2015. Ing. Massimo Tuccoli. Genova, 27 Febbraio 2015

ISO 9001:2015. Ing. Massimo Tuccoli. Genova, 27 Febbraio 2015 ISO 9001:2015. Cosa cambia? Innovazioni e modifiche Ing. Massimo Tuccoli Genova, 27 Febbraio 2015 1 Il percorso di aggiornamento Le principali novità 2 1987 1994 2000 2008 2015 Dalla prima edizione all

Dettagli

Il supporto del chirurgo generale. Giovanni Sgroi Direttore Dipartimento Scienze Chirurgiche U.O. Chirurgia Generale 2ª ed Oncologica A.O.

Il supporto del chirurgo generale. Giovanni Sgroi Direttore Dipartimento Scienze Chirurgiche U.O. Chirurgia Generale 2ª ed Oncologica A.O. Il supporto del chirurgo generale Giovanni Sgroi Direttore Dipartimento Scienze Chirurgiche U.O. Chirurgia Generale 2ª ed Oncologica A.O. Treviglio Rispettando il principio del trattamento guidato dai

Dettagli

Solutions in motion.

Solutions in motion. Solutions in motion. Solutions in motion. SIPRO SIPRO presente sul mercato da quasi trent anni si colloca quale leader italiano nella progettazione e produzione di soluzioni per il motion control. Porsi

Dettagli

Customer satisfaction and the development of commercial services

Customer satisfaction and the development of commercial services Customer satisfaction and the development of commercial services Survey 2014 Federica Crudeli San Donato Milanese, 27 May 2014 snamretegas.it Shippers day Snam Rete Gas meets the market 2 Agenda Customer

Dettagli

CODI/21 PIANOFORTE II // CODI/21 PIANO II

CODI/21 PIANOFORTE II // CODI/21 PIANO II MASTER di II livello - PIANOFORTE // 2nd level Master - PIANO ACCESSO: possesso del diploma accademico di II livello o titolo corrispondente DURATA: 2 ANNI NUMERO ESAMI: 8 (escluso l esame di ammissione)

Dettagli

Innovazione e ingegno

Innovazione e ingegno 10 Congresso Nazionale SEGI 26 Maggio 2015 Video Meeting SICHIG ISTERECTOMIA OGGI Innovazione e ingegno TECNICHE A CONFRONTO L. Frigerio Roma - Università Cattolica del Sacro Cuore Isterectomia Eseguita

Dettagli

HTA e screening. Paolo Giorgi Rossi AUSL Reggio Emilia

HTA e screening. Paolo Giorgi Rossi AUSL Reggio Emilia HTA e screening Paolo Giorgi Rossi AUSL Reggio Emilia L Aquila 20 Giugno 2012 Perchè? Obiettivi di un Sistema Sanitario Dare una risposta alle aspettative dei cittadini fornendo servizi di altà qualità

Dettagli

User Guide Guglielmo SmartClient

User Guide Guglielmo SmartClient User Guide Guglielmo SmartClient User Guide - Guglielmo SmartClient Version: 1.0 Guglielmo All rights reserved. All trademarks and logos referenced herein belong to their respective companies. -2- 1. Introduction

Dettagli

We take care of your buildings

We take care of your buildings We take care of your buildings Che cos è il Building Management Il Building Management è una disciplina di derivazione anglosassone, che individua un edificio come un entità che necessita di un insieme

Dettagli

GstarCAD 2010 Features

GstarCAD 2010 Features GstarCAD 2010 Features Unrivaled Compatibility with AutoCAD-Without data loss&re-learning cost Support AutoCAD R2.5~2010 GstarCAD 2010 uses the latest ODA library and can open AutoCAD R2.5~2010 DWG file.

Dettagli

I lipidi nella alimentazione del bambino. Carlo Agostoni Clinica Pediatrica, Ospedale San Paolo Università degli Studi di Milano

I lipidi nella alimentazione del bambino. Carlo Agostoni Clinica Pediatrica, Ospedale San Paolo Università degli Studi di Milano I lipidi nella alimentazione del bambino Carlo Agostoni Clinica Pediatrica, Ospedale San Paolo Università degli Studi di Milano ! I lipidi del latte materno: composizione e significato - acidi grassi -

Dettagli

You can visualize the free space percentage in Compact Flash memory from the MENU/INFO C.F. UTILITY-FREE SPACE page.

You can visualize the free space percentage in Compact Flash memory from the MENU/INFO C.F. UTILITY-FREE SPACE page. This release introduces some new features: -TUNE PITCH -FREE SPACE -TUNER -DRUMKIT EDITOR From the PARAM MIDI page, it is possible to modify the "TUNE PITCH" parameter, which allows you to tune up the

Dettagli

Pubblicazioni COBIT 5

Pubblicazioni COBIT 5 Pubblicazioni COBIT 5 Marco Salvato CISA, CISM, CGEIT, CRISC, COBIT 5 Foundation, COBIT 5 Trainer 1 SPONSOR DELL EVENTO SPONSOR DI ISACA VENICE CHAPTER CON IL PATROCINIO DI 2 La famiglia COBIT 5 3 Aprile

Dettagli

quali sono scambi di assicurazione sanitaria

quali sono scambi di assicurazione sanitaria quali sono scambi di assicurazione sanitaria These guides have a lot information especially advanced tips such as the optimum settings configuration for quali sono scambi di assicurazione sanitaria. QUALI

Dettagli

AVVISO n.12437. 03 Luglio 2014 --- Mittente del comunicato : Borsa Italiana. Societa' oggetto dell'avviso

AVVISO n.12437. 03 Luglio 2014 --- Mittente del comunicato : Borsa Italiana. Societa' oggetto dell'avviso AVVISO n.12437 03 Luglio 2014 --- Mittente del comunicato : Borsa Italiana Societa' oggetto dell'avviso : -- Oggetto : Modifiche al Manuale delle Corporate Actions - Amendment to the Corporate Action -

Dettagli

consenso informato (informed consent) processo decisionale condiviso (shared-decision making)

consenso informato (informed consent) processo decisionale condiviso (shared-decision making) consenso informato (informed consent) scelta informata (informed choice) processo decisionale condiviso (shared-decision making) Schloendorff. v. Society of NY Hospital 105 NE 92 (NY 1914) Every human

Dettagli

PRESENTAZIONE AZIENDALE ATTIVITA E SERVIZI TECNOLOGIE PERSONALE OBIETTIVI ESPERIENZE

PRESENTAZIONE AZIENDALE ATTIVITA E SERVIZI TECNOLOGIE PERSONALE OBIETTIVI ESPERIENZE PRESENTAZIONE AZIENDALE ABOUT US ATTIVITA E SERVIZI ACTIVITY AND SERVICES TECNOLOGIE TECHNOLOGIES PERSONALE TEAM OBIETTIVI OBJECTIVI ESPERIENZE PRESENTAZIONE AZIENDALE B&G s.r.l. è una società di progettazione

Dettagli

Il punto di vista del prescrittore

Il punto di vista del prescrittore Workshop Screening spontaneo e organizzato: l integrazione è possibile? 3.a Sessione: Doppio binario o integrazione? Moderatori Stefano Ciatto e Antonio Federici Il punto di vista del prescrittore (medico

Dettagli

Quando eseguire il test? Artioli Grazia Dipartimento di Scienze Mediche Onco-ematologia ULSS 13 Mirano Ve

Quando eseguire il test? Artioli Grazia Dipartimento di Scienze Mediche Onco-ematologia ULSS 13 Mirano Ve Quando eseguire il test? Artioli Grazia Dipartimento di Scienze Mediche Onco-ematologia ULSS 13 Mirano Ve The Opinion Pages Op-Ed Contributor My Medical Choice By ANGELINA JOLIE MAY 14, 2013, LOS ANGELES

Dettagli

MANUALE UTENTE MODULO ESPANSIONE TASTI MANUALE UTENTE MANUALE UTENTE Descrizione Il modulo fornisce al telefono VOIspeed V-605 flessibilità e adattabilità, mediante l aggiunta di trenta tasti memoria facilmente

Dettagli

TAVOLO DEGLI ENTI LOCALI PER IL CLIMA

TAVOLO DEGLI ENTI LOCALI PER IL CLIMA TAVOLO DEGLI ENTI LOCALI PER IL CLIMA 22 novembre VERSO LA STRATEGIA NAZIONALE DI ADATTAMENTO Responsabilità di Governo e competenze dei territori Sala Palazzo Bologna Senato della Repubblica Via di S.

Dettagli

up date basic medium plus UPDATE

up date basic medium plus UPDATE up date basic medium plus UPDATE Se si potesse racchiudere il senso del XXI secolo in una parola, questa sarebbe AGGIORNAMENTO, continuo, costante, veloce. Con UpDate abbiamo connesso questa parola all

Dettagli

CONFIGURATION MANUAL

CONFIGURATION MANUAL RELAY PROTOCOL CONFIGURATION TYPE CONFIGURATION MANUAL Copyright 2010 Data 18.06.2013 Rev. 1 Pag. 1 of 15 1. ENG General connection information for the IEC 61850 board 3 2. ENG Steps to retrieve and connect

Dettagli

Painting with the palette knife

Painting with the palette knife T h e O r i g i n a l P a i n t i n g K n i v e s Dipingere con la spatola Painting with the palette knife Made in Italy I t a l i a n M a n u f a c t u r e r La ditta RGM prende il nome dal fondatore

Dettagli

Scritto da DEApress Lunedì 14 Aprile 2014 12:03 - Ultimo aggiornamento Martedì 26 Maggio 2015 09:34

Scritto da DEApress Lunedì 14 Aprile 2014 12:03 - Ultimo aggiornamento Martedì 26 Maggio 2015 09:34 This week I have been walking round San Marco and surrounding areas to find things that catch my eye to take pictures of. These pictures were of various things but majority included people. The reason

Dettagli

Report dei gruppi di lavoro >> [ Mieloma multiplo ]

Report dei gruppi di lavoro >> [ Mieloma multiplo ] Report dei gruppi di lavoro >> [ Mieloma multiplo ] Relatore: M.T. PETRUCCI 27-28 ottobre 2008 Borgo S. Luigi Monteriggioni (Siena) Mieloma multiplo - Copyright FSE 1 Gruppo di lavoro 2 [ Mieloma multiplo]

Dettagli

Summary. Weekly Newsletter 6th November 2015. Dear Parents, We have many activities planned over the next few weeks leading to the winter break.

Summary. Weekly Newsletter 6th November 2015. Dear Parents, We have many activities planned over the next few weeks leading to the winter break. No Images? Click here Weekly Newsletter 6th November 2015 Summary Dear Parents, We have many activities planned over the next few weeks leading to the winter break. However, I will start by the General

Dettagli

Pavia, Giugno 2012. Gualtiero Palareti U.O. di Angiologia e Malattie della Coagulazione Policlinico S. Orsola-Malpighi Bologna

Pavia, Giugno 2012. Gualtiero Palareti U.O. di Angiologia e Malattie della Coagulazione Policlinico S. Orsola-Malpighi Bologna Pavia, Giugno 2012 Gualtiero Palareti U.O. di Angiologia e Malattie della Coagulazione Policlinico S. Orsola-Malpighi Bologna I principali problemi che vedo e il contributo delle ultime LG ACCP Diagnosi

Dettagli

LABORATORIO CHIMICO CAMERA DI COMMERCIO TORINO

LABORATORIO CHIMICO CAMERA DI COMMERCIO TORINO LABORATORIO CHIMICO CAMERA DI COMMERCIO TORINO Azienda Speciale della Camera di commercio di Torino clelia.lombardi@lab-to.camcom.it Criteri microbiologici nei processi produttivi della ristorazione: verifica

Dettagli

Impresa e innovazione nel settore energetico europeo: il contributo della conoscenza alla creazione di valore Silvia Bruzzi

Impresa e innovazione nel settore energetico europeo: il contributo della conoscenza alla creazione di valore Silvia Bruzzi ÉTUDES - STUDIES Impresa e innovazione nel settore energetico europeo: il contributo della conoscenza alla creazione di valore Silvia Bruzzi Polo Interregionale di Eccellenza Jean Monnet - Pavia Jean Monnet

Dettagli

ARRANGEMENT FOR A STUDENT EXCHANGE between University College London and The Scuola Normale Superiore, Pisa

ARRANGEMENT FOR A STUDENT EXCHANGE between University College London and The Scuola Normale Superiore, Pisa ARRANGEMENT FOR A STUDENT EXCHANGE between and The Scuola Normale Superiore, Pisa Preamble 1. The Faculty of Arts and Humanities (FAH) of (UCL) and the Scuola Normale Superiore of Pisa (SNS) have agreed

Dettagli

Can virtual reality help losing weight?

Can virtual reality help losing weight? Can virtual reality help losing weight? Can an avatar in a virtual environment contribute to weight loss in the real world? Virtual reality is a powerful computer simulation of real situations in which

Dettagli

Abstract Women Collection

Abstract Women Collection Abstract collection Head: J 271 Mod.: 3919 Body Col.: 287 Glossy White 2 Head: J 269 Body Col.: Glossy Black Mod.: 3965 3 Head: J 250 Mod.: 3966 Body Col.: 287 Glossy White 4 Head: J 248 Body Col.: 287

Dettagli

AVVISO n.17252 25 Settembre 2007

AVVISO n.17252 25 Settembre 2007 AVVISO n.17252 25 Settembre 2007 Mittente del comunicato : Borsa Italiana Societa' oggetto : dell'avviso Oggetto : Modifiche alle Istruzioni al Regolamento IDEM: Theoretical Fair Value (TFV)/Amendments

Dettagli

Il test valuta la capacità di pensare?

Il test valuta la capacità di pensare? Il test valuta la capacità di pensare? Per favore compili il seguente questionario senza farsi aiutare da altri. Cognome e Nome Data di Nascita / / Quanti anni scolastici ha frequentato? Maschio Femmina

Dettagli

1 1 0 /2 0 1 4. 0 n news

1 1 0 /2 0 1 4. 0 n news news n. 04 10/2011 VICO MAGISTRETTI KITCHEN ISPIRATION VIVO MAGIsTReTTI KITCHen IsPIRATIOn news Il nostro rapporto con il "Vico" è durato per più di quarant anni. era iniziato verso la metà degli anni

Dettagli

Differenze di sopravvivenza e percorsi di diagnosi e trattamento in Europa

Differenze di sopravvivenza e percorsi di diagnosi e trattamento in Europa L impatto dei tumori sui sistemi sanitari: approcci ed esperienze a confronto Aula Marconi, CNR, P.le Aldo Moro, 7 - Roma 4 febbraio 2014 Differenze di sopravvivenza e percorsi di diagnosi e trattamento

Dettagli

U Corso di italiano, Lezione Quindici

U Corso di italiano, Lezione Quindici 1 U Corso di italiano, Lezione Quindici U Buongiorno, anche in questa lezione iniziamo con qualche dialogo formale M Good morning, in this lesson as well, let s start with some formal dialogues U Buongiorno,

Dettagli

PROGETTO PAP TEST. Help for Life. MAM Beyond borders

PROGETTO PAP TEST. Help for Life. MAM Beyond borders PROGETTO PAP TEST Help for Life MAM Beyond borders INTRODUZIONE L International Agency for Research of Cancer (WHO) riporta: Cervical cancer is the fourth most common cancer in women, and the seventh overall,

Dettagli

Newborn Upfront Payment & Newborn Supplement

Newborn Upfront Payment & Newborn Supplement ITALIAN Newborn Upfront Payment & Newborn Supplement Female 1: Ormai manca poco al parto e devo pensare alla mia situazione economica. Ho sentito dire che il governo non sovvenziona più il Baby Bonus.

Dettagli

ISLL Papers The Online Collection of the Italian Society for Law and Literature http://www.lawandliterature.org/index.php?

ISLL Papers The Online Collection of the Italian Society for Law and Literature http://www.lawandliterature.org/index.php? The Online Collection of the Italian Society for Law and Literature http://www.lawandliterature.org/index.php?channel=papers ISLL - ITALIAN SOCIETY FOR LAW AND LITERATURE ISSN 2035-553X Submitting a Contribution

Dettagli

PIANO DI STUDI. Primo anno di corso

PIANO DI STUDI. Primo anno di corso PIANO DI STUDI Laurea in Economia, commercio internazionale e mercati finanziari (DM 270/04) L-33 Bachelor degree in Italian and in English (2 curricula in English) 1) CURRICULUM: Economia internazionale

Dettagli

no. SIC04053.03 Rev. 00 Dated 2008.10.02

no. SIC04053.03 Rev. 00 Dated 2008.10.02 TECHNICAL REPORT RAPPORTO TECNICO no. SIC04053.03 Rev. 00 Dated 2008.10.02 This technical report may only be quoted in full. Any use for advertising purposes must be granted in writing. This report is

Dettagli

Ingegneria del Software Testing. Corso di Ingegneria del Software Anno Accademico 2012/2013

Ingegneria del Software Testing. Corso di Ingegneria del Software Anno Accademico 2012/2013 Ingegneria del Software Testing Corso di Ingegneria del Software Anno Accademico 2012/2013 1 Definizione IEEE Software testing is the process of analyzing a software item to detect the differences between

Dettagli

www.gimsi.it Registro GIMSI

www.gimsi.it Registro GIMSI www.gimsi.it Registro GIMSI Registro GIMSI Board: Ammirati if Badami A Brignole M (responsabile progetto) Casagranda I De Seta F Furlan R Registro multicentrico prospettico costituito dai pazienti valutati

Dettagli

Diversity: un opportunità per il business Diversity: a key business opportunity. Che cos è Parks What is Parks?

Diversity: un opportunità per il business Diversity: a key business opportunity. Che cos è Parks What is Parks? Diversity: un opportunità per il business Diversity: a key business opportunity In un clima economico in cui ogni azienda si trova di fronte alla necessità di razionalizzare le proprie risorse e di massimizzare

Dettagli

Famiglie di tabelle fatti

Famiglie di tabelle fatti aprile 2012 1 Finora ci siamo concentrati soprattutto sulla costruzione di semplici schemi dimensionali costituiti da una singola tabella fatti circondata da un insieme di tabelle dimensione In realtà,

Dettagli

A Solar Energy Storage Pilot Power Plant

A Solar Energy Storage Pilot Power Plant UNIONE DELLA A Solar Energy Storage Pilot Power Plant DELLA Project Main Goal Implement an open pilot plant devoted to make Concentrated Solar Energy both a programmable energy source and a distribution

Dettagli

Domanda. L approccio interprofessionale in sanità: razionale ed evidenze. Programma. Programma

Domanda. L approccio interprofessionale in sanità: razionale ed evidenze. Programma. Programma Domanda L approccio interprofessionale in sanità: razionale ed evidenze Perché è necessario un approccio interprofessionale in sanità? Giorgio Bedogni Unità di Epidemiologia Clinica Centro Studi Fegato

Dettagli

Esercizi Programming Contest

Esercizi Programming Contest Esercizi Programming Contest Alberto Montresor 22 maggio 2012 Alcuni degli esercizi che seguono sono associati alle rispettive soluzioni. Se il vostro lettore PDF lo consente, è possibile saltare alle

Dettagli

Italian Journal Of Legal Medicine

Italian Journal Of Legal Medicine Versione On Line: ISSN 2281-8987 Italian Journal Of Legal Medicine Volume 1, Number 1. December 2012 Editore: Centro Medico Legale SRL - Sede Legale: Viale Brigata Bisagno 14/21 sc D 16121 GENOVA C.F./P.IVA/n.

Dettagli

Integrazione degli approcci molecolare e bioinformatico al profiling molecolare delle linee cellulari di tumore della mammella estrogeno responsivo

Integrazione degli approcci molecolare e bioinformatico al profiling molecolare delle linee cellulari di tumore della mammella estrogeno responsivo Integrazione degli approcci molecolare e bioinformatico al profiling molecolare delle linee cellulari di tumore della mammella estrogeno responsivo 16 novembre 2004 Studio comparativo dei profili di espressione

Dettagli

La gestione dell urgenza cardiologica: il punto di vista del medico d urgenza Ivo Casagranda

La gestione dell urgenza cardiologica: il punto di vista del medico d urgenza Ivo Casagranda La gestione dell urgenza cardiologica: il punto di vista del medico d urgenza Ivo Casagranda Key points: 1 Funzioni e organizzazione del PS 2 Position paper ANMCO SIMEU 3 Real world It is one thing to

Dettagli

IL PERCORSO DI AMD PER LA MEDICINA DI GENERE: dalle differenze di genere alle pari opportunità

IL PERCORSO DI AMD PER LA MEDICINA DI GENERE: dalle differenze di genere alle pari opportunità 1 Giornata Nazionale del Gruppo Donna IL PERCORSO DI AMD PER LA MEDICINA DI GENERE: dalle differenze di genere alle pari opportunità Olbia, 16 e 17 marzo 2012 Mercure Olbia Hermaea Il Gruppo Donna di AMD:

Dettagli

AVVISO n.14114 08 Settembre 2009

AVVISO n.14114 08 Settembre 2009 AVVISO n.14114 08 Settembre 2009 Mittente del comunicato : Borsa Italiana Societa' oggetto : dell'avviso Oggetto : Modifiche alle Istruzioni: Codice di Autodisciplina/Amendemnts to the Instructions: Code

Dettagli

E-Business Consulting S.r.l.

E-Business Consulting S.r.l. e Rovigo S.r.l. Chi siamo Scenario Chi siamo Missione Plus Offerti Mercato Missionedi riferimento Posizionamento Metodologia Operativa Strategia Comunicazione Digitale Servizi Esempidi consulenza Clienti

Dettagli

Il delirium: problematiche extraospedaliere

Il delirium: problematiche extraospedaliere Roma, 19 marzo 2015 Il delirium: problematiche extraospedaliere Marco Trabucchi Università di Roma Tor Vergata Gruppo di Ricerca Geriatrica, Brescia Associazione Italiana Psicogeriatria 1 Intensive Care

Dettagli

http://www.homeaway.it/info/guida-proprietari Copyright HomeAway INC

http://www.homeaway.it/info/guida-proprietari Copyright HomeAway INC Cambiare il testo in rosso con i vostri estremi Esempi di lettere in Inglese per la restituzione o trattenuta di acconti. Restituzione Acconto, nessun danno all immobile: Vostro Indirizzo: Data

Dettagli

DESTINAZIONE EUROPA. BOARDING PASS PER LE MARIE CURIE FELLOWSHIP Focus sul capitolo B4 IMPLEMENTATION

DESTINAZIONE EUROPA. BOARDING PASS PER LE MARIE CURIE FELLOWSHIP Focus sul capitolo B4 IMPLEMENTATION A P R E AGENZIA P E R L A PROMOZIONE D E L L A RICERCA EUROPEA DESTINAZIONE EUROPA BOARDING PASS PER LE MARIE CURIE FELLOWSHIP Focus sul capitolo B4 IMPLEMENTATION Di Angelo D Agostino con la collaborazione

Dettagli

UNI EN ISO 12944-6. Corrosion protection of steel structures by protective paint systems. Laboratory performance test for

UNI EN ISO 12944-6. Corrosion protection of steel structures by protective paint systems. Laboratory performance test for via di Marmiceto, 6/C-56016 Ospeetto PISA P.IVA 01115340505 CCIAA Pi 101169 Report n 2050451/5 UNI EN ISO 12944-6 Corrosion protection of steel structures by protective paint systems Laboratory performance

Dettagli

Renzo Andrich renzo.andrich@siva.it

Renzo Andrich renzo.andrich@siva.it Gruppo di Studio SIGG La cura nella fase terminale della vita sostenuto da un contributo non condizionato della Fondazione Alitti SOSTENIBILITA DELLE CURE DI FINE VITA TRA CULTURA E ORGANIZZAZIONE Bologna

Dettagli

English-Medium Instruction: un indagine

English-Medium Instruction: un indagine English-Medium Instruction: un indagine Marta Guarda Dipartimento di Studi Linguistici e Letterari (DiSLL) Un indagine su EMI presso Unipd Indagine spedita a tutti i docenti dell università nella fase

Dettagli

Settori Applicativi Field of Application

Settori Applicativi Field of Application ERIMAKI Brochure_23 Luglio_okDEFINITIVO_Layout 1 23/07/12 12.51 Pagina 1 Settori Applicativi Field of Application Trattamento Plastica Plastic treatment Legno e Vetro Wood and glass Stoccaggio Storage

Dettagli

touch&spot 0 V E R 2 1 3 0 FULL - 5 Medical functions 0 V E R 2 1 4 0 I.P.L. - 3 Medical functions 0 V E R 2 1 4 5 DEPY - 2 Funzioni

touch&spot 0 V E R 2 1 3 0 FULL - 5 Medical functions 0 V E R 2 1 4 0 I.P.L. - 3 Medical functions 0 V E R 2 1 4 5 DEPY - 2 Funzioni R E S O L U T I O N I. P. L. touch&spot 0 V E R 2 1 3 0 FULL - 5 Medical functions 0 V E R 2 1 4 0 I.P.L. - 3 Medical functions 0 V E R 2 1 4 5 DEPY - 2 Funzioni SCEGLI RESOLUTION I.P.L. LAVORA IN LIBERTÀ

Dettagli