Federica Perelli

HIPEC in recurrent ovarian cancer patients: Morbidity-related treatment and long-term analysis of clinical outcome

OBJECTIVE To evaluate morbidity and mortality rates associated with the use of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) after optimal cytoreduction (CRS) in a large single-institutional series of platinum-sensitive recurrent ovarian cancer patients. Moreover, disease free (DFS) and overall survival (OS) of previously studied patients have been assessed after a longer follow-up period. METHOD From May 2005 to October 2010, recurrent ovarian cancer patients with a platinum-free interval of at least 6 months have been prospectively enrolled in a protocol of CRS plus HIPEC with oxaplatinum (460 mg/m(2)) heated to 41.5 °C for 30 min, followed by 6 cycles of systemic chemotherapy with taxotere 75 mg/m(2) and oxaliplatin 100 mg/m(2). RESULTS Forty-one patients experienced 43 procedures (CRS+HIPEC). An optimal cytoreduction was achieved in all cases (CC-0 95.3%; CC-1 4.7%). A complication rate of 34.8% was registered, with no case of intraoperative death or within 30 days after surgery. Survival curves have been calculated in a group of 25 patients with a minimum follow-up of 18 months, obtaining a median DFS and OS of 24 (range 6-60) and 38 months (range 18-60), respectively. CONCLUSION In recurrent platinum-sensitive ovarian cancer patients, the use of CRS plus HIPEC represents a safe treatment, able to significantly influence the survival rates compared to chemotherapy alone or surgery plus standard chemotherapy.

Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD): A systematic review of randomized clinical trials

BACKGROUND The treatment of postpartum depression with selective serotonin reuptake inhibitors (SSRIs) has been claimed to be both efficacious and well tolerated, but no recent systematic reviews have been conducted. METHODS A qualitative systematic review of randomized clinical trials on women with postpartum depression comparing SSRIs to placebo and/or other treatments was performed. A comprehensive literature search of online databases, the bibliographies of published articles and grey literature were conducted. Data on efficacy, acceptability and tolerability were extracted and the quality of the trials was assessed. RESULTS Six randomised clinical trials, comprising 595 patients, met quality criteria for inclusion in the analysis. Cognitive-behavioural intervention, psychosocial community-based intervention, psychodynamic therapy, cognitive behavioural therapy, a second-generation tricyclic antidepressant and placebo were used as comparisons. All studies demonstrated higher response and remission rates among those treated with SSRIs and greater mean changes on depression scales, although findings were not always statistically significant. Dropout rates were high in three of the trials but similar among treatment and comparison groups. In general, SSRIs were well tolerated and trial quality was good. LIMITATIONS There are few trials, patients included in the trials were not representative of all patients with postpartum depression, dropout rates in three trials were high, and long-term efficacy and tolerability were assessed in only two trials. CONCLUSIONS SSRIs appear to be efficacious and well tolerated in the treatment of postpartum depression, but the available evidence fails to demonstrate a clear superiority over other treatments.

How to Manage Bowel Endometriosis: The ETIC Approach

A panel of experts in the field of endometriosis expressed their opinions on management options in a 35-year-old patient desiring pregnancy with a history of previous surgery for endometrioma and bowel obstruction symptoms. Many questions that this paradigmatic patient may pose to the clinician are addressed, and various clinical scenarios are discussed. A decision algorithm derived from this discussion is proposed as well.

Current Recommendations for Minimally Invasive Surgical Staging in Ovarian Cancer

Opinion statementMinimally invasive surgery (MIS) currently is performed to stage and treat ovarian cancer at different stages of disease; however, the higher level of evidence from existing studies is IIB. Despite the absence of randomized controlled trials, MIS represents a safe and adequate procedure for treating and staging early ovarian cancer, and its use has increased significantly in clinical practice. Major concerns are related to minimizing tumor disruption or dissemination, removing the adnexal mass intact, adequate retroperitoneal staging, and fertility-sparing surgery for young patients. The main goal for patients with advanced ovarian cancer is to determine the best therapeutic strategy by evaluating the risks and benefits of primary debulking surgery versus neoadjuvant chemotherapy followed by interval debulking surgery. The use of staging laparoscopy in patients with advanced epithelial ovarian cancer appears to be the most researched and accepted approach. Regarding other types and stages of ovarian cancer, although the evidence is very promising, clinical trials performed by expert gynecologic oncology surgeons in referral centers are still needed to prove the efficacy of such an approach in these patients. In particular, MIS has provided an opportunity to remove localized recurrences, with both retroperitoneal and intraperitoneal diffusion.

Management of osteogenesis imperfecta type I in pregnancy; a review of literature applied to clinical practice

PurposeOsteogenesis imperfecta (OI) is a rare heritable heterogenous disorder characterized by bone fragility and susceptibility to fractures with a wide spectrum of clinical expression due to defects in collagen type I biosynthesis. The purpose of the review is to highlight the practical norms in pregnancies with osteogenesis imperfecta.MethodsWe carried out a literature review in MEDLINE on OI during pregnancy, focusing on diagnosis, therapy and delivery. We reviewed 28 articles (case reports, original articles and reviews).ResultsPregnant women affected by type I OI should be closely monitored to assess fetal well-being and detect pregnancy-related complications associated with an increased risk for osteoporosis, restrictive pulmonary disease, cephalopelvic disproportion and other problems related to connective tissue disorders. Mode of delivery remains controversial and should be determined on an individual basis.ConclusionIn conclusion, women affected by type I OI represent a subset of patients whose pregnancies should be considered high risk and warrant a multidisciplinary approach in a referral center.

Dysmenorrhea and related disorders

Dysmenorrhea is a common symptom secondary to various gynecological disorders, but it is also represented in most women as a primary form of disease. Pain associated with dysmenorrhea is caused by hypersecretion of prostaglandins and an increased uterine contractility. The primary dysmenorrhea is quite frequent in young women and remains with a good prognosis, even though it is associated with low quality of life. The secondary forms of dysmenorrhea are associated with endometriosis and adenomyosis and may represent the key symptom. The diagnosis is suspected on the basis of the clinical history and the physical examination and can be confirmed by ultrasound, which is very useful to exclude some secondary causes of dysmenorrhea, such as endometriosis and adenomyosis. The treatment options include non-steroidal anti-inflammatory drugs alone or combined with oral contraceptives or progestins.

Successful Obstetric Management of Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic myocardial disorder characterized by the replacement of myocardium by fibro-adipose tissue. The proper obstetric management of this disease remains unclear due to the lack of an adequate number of cases reported in the literature. We report the successful management of a pregnant patient with ARVC. A female patient with ARVC presented to our hospital at 9 weeks of gestation. Before pregnancy, she was treated with bisoprolol, which resulted in a reduction in extrasystoles and she never developed palpitations. Periodical cardiological examinations showed clinical stability, and the only therapeutic change consisted of an increase in the bisoprolol dosage. She delivered at term by elective cesarean section. We decided that avoiding changes in the chronic therapy of our patient was the best management because she had reached clinical stability before pregnancy and discontinuation of therapy may pose an addition risk. In our opinion, cesarean section was the best mode of delivery in our ARVC patient to avoid the stress of labor, which may raise heart rate and cause arrhythmia. Our experience and the case reports in the literature suggest that pregnancy is tolerated in female patients with ARVC, but they need to be monitored during pregnancy by a multidisciplinary team.

Keep in mind foetomaternal haemorrage in case of reduced foetal movements: a successful obstetric management

Foetomaternal blood exchange occurs in about 50–75% of pregnancies with an unclear physiopathology. Foetomaternal haemorrhage (FMH) is a poorly understood clinical condition with an incidence of between 0.3 and 1, over 1000 deliveries (Sueters et al. 2003). This clinical condition seems to be responsible for 14% of perinatal deaths of unknown cause, and several studies suggest that there is a potential link between FMH and decreased or absent foetal movements, sinusoidal foetal heart rate pattern, stillbirths and hydrops foetalis (Giacoia 1997). If this condition is suspected, the delivery and neonatal blood transfusion if necessary represent an appropriate management in addition to the Kleihauer–Betke test to confirm the diagnosis. We describe a case of FMH of unknown cause, in which reduced foetal movements were associated with severe neonatal anaemia.

Ultrasonographic early diagnosis of osteogenesis imperfecta type I: implications for pre and post-natal therapy

We have read with great interest the ‘Letter to the Editor’ by Takahashi et al. [1] related to our article. We agree with Takahashi et al. that osteogenesis imperfecta (OI) is a serious disease for both mother and fetus. Cozzolino et al. [2] defined the proper monitoring and treatment of women affected by OI during pregnancy to minimize maternal and fetal risks, and in that case the fetus was not affected. Takahashi et al. suggested the fetal surveillance, proposed ultrasound features, the increased nuchal translucency (NT) and thin skull bone, as instrument to formulate an early suspected diagnosis of OI type I. The infant of their case showed blue sclerae and thinner skull, clinically consistent with OI type I, but the current lack of genetic testing does not allow to make a definite correlation. In our opinion these are really relevant observations. If increased NT can be not specific, thin skull bone can be a more selective marker. It will be essential to find a precise definition of thin skull bone and ultrasonographic cut-off will be necessary. Although other studies will be required to confirm this observation, we can assume an interesting clinical use of this information. During the pre-conception counseling or at the first pre-natal visit of patients suffering from OI, clinicians will eventually propose to proceed with the noninvasive ultrasound identification of these two signs, in order to provide a diagnostic hypothesis on fetus health. Patients can use this ultrasound information to improve their decision to carry out or not an invasive diagnosis with chorionic villus sampling or amniocentesis, which remains the only current alternative for a certain diagnosis. If the NT and thin skull bone may allow early diagnosis of this disease, which are the therapeutic implications of this early diagnosis of OI type I? What life prospects can have these children? Osteogenesis imperfecta (OI) is a genetic disorder of mesenchymal cells characterized by defective type I collagen, the major structural protein in bone. Patients with severe OI have numerous painful fractures, progressive skeletal deformities, and retarded bone growth, resulting in short stature. There is no cure for OI, and only one class of drugs, the bisphosphonates, has shown therapeutic potential [3]. Mesenchymal stem cells (MSCs) are bone marrowderived mesenchymal progenitors that can serve as longterm precursors for the regeneration of a variety of nonhematopoietic tissues, including bone, cartilage, muscle, and possibly neural elements [4]. MSCs have the potential to improve skeletal damage. The potential of MSC transplantation for OI was demonstrated initially in the mouse, in which allogeneic transplanted wild-type donor MSCs homed to the bones, in these cases they have increase the osteoprogenitor pool, with an increase in the mechanisms of mineralization and collagen deposition. Later the same therapy has been tested in a clinical trial in children with severe forms of OI type III treated with infusion of MSCs. They have been reported increases in skeletal mineralization and the speed of growth, despite a low level of engraftment (*1 %) [5]. A very promising therapeutic approach was identified by Götherström et al. [6], with the use of mesenchymal stem cells (MSCs) transplantation pre and post-natal. Götherström et al. reported clinical course of two patient with OI, received prenatal human fetal MSCs transplantation and postnatal hosting with same donor MSCs. However both cases were not OI type I, but type III and IV, which are much more severe forms of OI [6]. In conclusion an & Mauro Cozzolino maurocoz@yahoo.it

Peripartum and postpartum outcomes in uncomplicated term pregnancy following ART: a retrospective cohort study from two Italian obstetric units

Abstract STUDY QUESTION Do singleton uncomplicated term pregnancies conceived by assisted reproductive technology (ART) have adverse peripartum and postpartum outcomes? SUMMARY ANSWER Term pregnancies following ART, even if uncomplicated until birth, have a higher risk of retained placenta and postpartum hemorrhage (PPH). WHAT IS KNOWN ALREADY There is consistent evidence that pregnancies following ART have higher incidence of complications during pregnancy. However, few studies specifically investigated birth outcomes in ART term pregnancies. STUDY DESIGN, SIZE, DURATION A retrospective cohort study was conducted on 14 415 deliveries at two university tertiary care obstetric units. Clinical data were extracted by reviewing obstetric records of all deliveries from 1 January 2010 to 31 December 2014, in a standardized electronic database regarding the mother’s health before and during pregnancy, complications during pregnancy and at birth, and neonatal outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS Following an accurate evaluation of exclusion criteria (multiparity, maternal pre-pregnancy diseases, prior uterine surgery, fetal malformations, intrauterine deaths, elective cesarean section and pregnancy complications), the group of uncomplicated singleton term pregnancies from autologous ART conception by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (n = 188) was compared with a maternal age and body mass index (BMI) matched group of spontaneous pregnancies (n = 1168). Cases of intrauterine insemination (IUI) (n = 14) and ovulation induction with timed intercourse (n = 18) were not included. Labor, delivery and postpartum outcomes were evaluated. Odds ratios (OR) were adjusted with multivariable logistic regression to maternal age, BMI, nationality and gestational age at birth. MAIN RESULTS AND THE ROLE OF CHANCE The age of women in the final analysis ranged from 25 to 45 years, while BMI ranged from 17 to 34 kg/m2. Uncomplicated term pregnancies with ART conception had a higher risk of operative delivery (adjusted OR 1.40, 95% confidence interval (CI) 1.01–1.95), retained placenta (adjusted OR 2.63, 95% CI 1.31–5.26) and PPH (adjusted OR 2.86 95% CI 1.37–5.99). Conversely, ART conception did not increase the risk of induced labor (adjusted OR 1.18, 95% CI 0.85–1.65). However, patients that conceived by ART and underwent labor induction had a higher risk of failed induction compared with the control group (adjusted OR 2.53, 95% CI 1.23–5.21). Infants born after ART had a similar birthweight, Apgar score and arterial blood pH compared with spontaneously-conceived ones. LIMITATIONS, REASONS FOR CAUTION The database lacked specific information about causes of infertility, smoking habit, family income and details on ART (fresh versus frozen cycle, IVF versus ICSI), limiting, in part, our analysis of the results. However, only autologous IVF/ICSI pregnancies were included in order to prevent bias related to conception by oocyte/embryo donation. In vivo conception ART cases were excluded because they were too few to allow comparison with IVF/ICSI. Nevertheless, the inclusion of only uncomplicated pregnancies provides a highly homogeneous and still representative population sample. Study sample is representative of a well-resourced obstetric facility in a high-income country, limiting to some extent the generalizability of study results. WIDER IMPLICATIONS OF THE FINDINGS Pregnancies conceived by autologous ART that proceed uncomplicated until term may require counseling about the risk of placental retention with PPH. STUDY FUNDING/COMPETING INTERESTS The authors have no conflict of interest and funding to declare.