Nicolò Bizzarri

Dienogest in the treatment of endometriosis

Introduction: Dienogest (DNG) is an oral progestin, derivative of 19-nortestosterone, that has recently been introduced for the treatment of endometriosis. Areas covered: This review examines the clinical efficacy, safety and tolerability of DNG in the treatment of endometriosis. The material included in the current manuscript was searched and obtained via Medline, Pubmed and EMBASE, from inception until February 2014. The term ‘dienogest’ was associated with the following search terms: ‘endometriosis’, ‘pharmacokinetics’, ‘safety’ and ‘efficacy’. Expert opinion: Several trials demonstrated the clinical efficacy, safety and tolerability of DNG. However the use of DNG is associated with some limitations. So far, no study investigated the potential of contraceptive effect of this treatment and therefore, it should be recommended with other methods of contraception (e.g., barrier methods). A further limitation of the use of DNG as daily therapy in the long term is that the cost of the therapy is higher than other progestins available on the market and combined oral contraceptives. Therefore, future studies should be designed to compare the efficacy and safety of DNG with other progestins.

Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study

OBJECTIVE To compare the usefulness of preoperative treatment with triptorelin, letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas. STUDY DESIGN Single center prospective non-randomized comparative pilot study. The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas graded as type 0, type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm. Exclusion criteria were: associated polyps, associated non-hysteroscopic surgical procedures, >2 myomas requiring hysteroscopic resection. This study enrolled patients who underwent either direct surgery (group S; n=23) or 3-month preoperative treatment with triptorelin (3.75 mg every 28 days; group T; n=20), letrozole (2.5 mg/day; group L; n=11) or ulipristal acetate (5 mg/day; group U; n=7). Patients underwent hysteroscopic resection of the myomas. RESULTS All medical treatments caused a significant decrease in the volume of myomas (group T, p<.001; group L, p<.001; group U, p=.006); however, the percentage decrease in myoma volume was lower in group U than in group T (p=.001) and in group L (p=.010). The hysteroscopy time was higher in group S than in group T (p<.001) and in group L (p=.001); there was no significant difference in the hysteroscopy time between group S and group U (p=.206). Fluid absorption was lower in group T than in group S (p=.002) and in group L than in group S (p=.048); fluid absorption was similar in group S and group U (p=.110). Intra- and postoperative complications, postoperative pain, and patient satisfaction were similar in the four study groups. Surgeons evaluation of operative difficulty was better in group T than in group S (p<.005). CONCLUSIONS Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas.

Bevacizumab for the treatment of cervical cancer

ABSTRACT Introduction: Cervical cancer is still a major cause of morbidity and mortality in women. Early stages and locally advanced cervical cancer are currently treated respectively with surgery and chemoradiation with good prognosis. Persistent, recurrent and metastatic cervical cancers have a poor prognosis. Angiogenesis has been identified as a crucial factor for cervical cancer growth. Recently, research has increasingly focused on the development of targeted therapies, such as anti-angiogenic drugs. Amongst such drugs, bevacizumab, a recombinant humanized monoclonal antibody has been the subject of extensive investigation, including its use in cervical cancer. This was recently approved for the treatment of patients with metastatic, recurrent, or persistent cervical cancer. Areas covered: The aim of this review is to discuss the role of bevacizumab in both locally advanced and metastatic or recurrent cervical cancer and to analyze the studies that have led to the approval of bevacizumab in cervical cancer. Expert opinion: The use of bevacizumab in combination with other chemotherapies in cervical cancer has been proven safe and effective, with a significant improvement in overall survival of patients with advanced cervical cancer. Combination therapy using bevacizumab has been demonstrated to increase toxicity rates but it does not impair patient’s quality of life.

Drug safety evaluation of ulipristal acetate in the treatment of uterine fibroids

Introduction: Ulipristal acetate (UPA) is a selective progesterone-receptor modulator (SPRM). SPRMs are a new class of progesterone-receptor ligands that exert tissue selective agonist, antagonist or mixed agonist–antagonist activity in target cells. UPA inhibits the proliferation, induces apoptosis of leiomyoma cells in vitro and demonstrates potent progesterone antagonist activity in vitro and in vivo. Areas covered: This manuscript aims to review the available data on safety of UPA in the treatment of uterine fibroids. Data and articles included in this manuscript were obtained via PubMed, Medline and Embase up to November 2014. Expert opinion: UPA is efficacious in the treatment of uterine fibroids before surgery; it decreases leiomyoma volume and uterine bleeding; furthermore, it improves quality of life. Short-term administration of UPA has been shown to be safe at short follow-up (months) and it is associated with minimal adverse side effects; further studies with longer follow-up are required to define the safety profile of UPA on endometrial histology.

Pharmacokinetic and pharmacodynamic profile of dronedarone, a new antiarrhythmic agent for the treatment of atrial fibrillation

Introduction: Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects. Areas covered: This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial). Expert opinion: Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone’s pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF.

Symptomatic endometriosis of the posterior cul-de-sac is associated with impaired sleep quality, excessive daytime sleepiness and insomnia: a case–control study

OBJECTIVE To assess the impact of endometriosis of the posterior cul-de-sac on quality of sleep, average daytime sleepiness and insomnia. STUDY DESIGN This age-matched case-control study was conducted in a tertiary referral centre for the diagnosis and treatment of endometriosis between May 2012 and December 2013. It included 145 women with endometriosis of the posterior cul-de-sac (cases; group E) and 145 patients referred to our Institution because of routine gynaecologic consultations (controls; group C). This study investigated whether sleep is impaired in patients with endometriosis of the posterior cul-de-sac. Sleep quality, daytime sleepiness and insomnia were assessed using the following self-administered questionnaires: the Pittsburgh Sleep Quality Index, the Epworth sleepiness scale and the Insomnia Severity Index, respectively. The primary objective of the study was to evaluate sleep quality in the two study groups. Secondary outcomes of the study were to assess average daytime sleepiness and insomnia in the two study groups. RESULTS The prevalence of poor sleep quality was significantly higher in group E (64.8%) than in group C (15.1%; p<0.001). The prevalence of excessive daytime sleepiness was significantly higher in group E (23.4%) than in group C (12.9%; p=0.033). Patients of group E experienced subthreshold insomnia (29.0%) and moderate clinical insomnia (16.6%) significantly more frequently than patients in group C (24.4% and 5.0%; p=0.002). CONCLUSION A substantial proportion of women with endometriosis of the posterior cul-de-sac experiences poor sleep quality, excessive daytime sleepiness and insomnia.

Intraoperative Transrectal Ultrasonography for Hysteroscopic Metroplasty: Feasibility and Safety.

The primary objective of this prospective comparative nonrandomized study was to assess the feasibility and safety of intraoperative transrectal ultrasonography (TRUS) during hysteroscopic metroplasty (HM). The secondary objective of the study was to assess whether TRUS facilitates complete removal of the uterine septum. Septate uterus was diagnosed by 3-dimensional transvaginal ultrasonography (3D-TVS) and confirmed by magnetic resonance imaging. In the control group (HM group; n = 18), patients underwent HM according to the traditional standard of operative hysteroscopy. In the study group (HM+TRUS group; n = 27), HM and TRUS were performed simultaneously; the hysteroscopic procedure was continued until a normal uterine fundus was observed. At 6 to 8 weeks after HM, 3D-TVS was performed to identify the numbers of complete resections (residual septum absent or <5 mm), suboptimal resections (residual septum 5-10 mm), and incomplete resections (residual septum > 10 mm). The 2 study groups did not differ significantly in terms of demographic and clinical characteristics, or in the volume of fluid infused and absorbed. There were no severe intraoperative or postoperative complication in either group; 2 patients in the HM+TRUS group and 1 patient in the HM group experienced urinary tract infection (p = .807). At 6 to 8 weeks after HM, the number of suboptimal resections and incomplete resections was higher in the HM group than in the HM+TRUS group (p = .031). Residual septum >10 mm (incomplete resection) was seen in 1 patient in the HM group but in no patients in the HM+TRUS group. Intraoperative TRUS can be performed safely during HM, and may increase the likelihood of complete resection of the uterine septum; however, this finding should be confirmed by larger studies.

Cutaneous metastasis from vulvar squamous cell carcinoma: a rare occurrence that should not be forgotten

Abstract Vulvar cancer accounts for 5% of the female genital tract cancers. Cutaneous metastases from vulvar cancer are extremely rare and for this reason, it can be difficult to reach a diagnosis with a consequent delay in the treatment. A systematic literature review of articles on this subject was conducted through a MEDLINE-based search for articles published in English or French. To date, 16 cases (including ours unpublished) of cutaneous metastasis from vulvar cancer have been reported. Cutaneous metastasis can occur from any stage of vulvar cancer, even after a short period. Different treatments have been described but none of them seems to be more effective. In all reported cases the prognosis was very poor. Every time a vulvar cancer survivor shows a suspicious cutaneous lesion, this should be biopsied to exclude skin relapse. Impact statement Cutaneous metastases from vulvar cancer are extremely rare and due to its rarity, a standard treatment has not been established yet. Cutaneous metastasis can occur from any stage of vulvar cancer, even after a short period. In all the reported cases, the prognosis was very poor. Every time a vulvar cancer survivor shows a suspect cutaneous lesion, this should be biopsied to exclude skin relapse.

Peritoneal carcinomatosis from ovarian paraganglioma: Report of a rare case and systematic review of the literature

Paraganglioma is one of the rarest neoplasms involving the ovary, with only 10 previous reports. We present a case of peritoneal carcinomatosis from primary ovarian paraganglioma and a systematic review of the literature. Clinical information was retrieved from medical records, and a systematic review of the literature was performed according to meta‐analysis of observational studies in epidemiology guidelines. A 33‐year‐old woman presented with a 12‐month history of hypertension and weight loss. She was diagnosed with ovarian paraganglioma and was treated with extensive debulking surgery to no residual disease after three cycles of neoadjuvant chemotherapy. She recurred after 6 months and was started on somatostatin‐analogue. Following further disease progression with bone metastasis (treated with palliative radiotherapy), a trial with Sunitinib was started. The patient died 30 months after initial diagnosis. Of the cases reported to date, only one had peritoneal metastasis at presentation but none of them had such an ominous prognosis. Ovarian paraganglioma is an extremely rare condition. We report the first case of primary malignant ovarian paraganglioma with an exceptionally aggressive behavior. Clinicopathological correlation with immunohistochemistry is essential to avoid misdiagnosis. A standard treatment is not recommended yet but cytoreductive surgery seems to be a favorable approach to prolong survival.

Complete response in a patient with gynecological hidradenocarcinoma treated with exclusive external beam radiotherapy and brachytherapy: a case report

Hidradenocarcinoma (HC) is a very rare disease. This case report illustrates a successful treatment of a 60-year-old woman with vulvo-vaginal localization of hidradenocarcinoma treated with external beam radiotherapy delivered by helical tomotherapy with a simultaneous integrated boost (SIB), followed by brachytherapy. External beam radiotherapy dose prescription was 50.4 Gy in 28 fractions, five fractions per week to whole pelvis (planning target volume 1 – PTV1), 60.2 Gy in 28 fractions to SIB1 (fundus of uterus and right inguinal node), and 58.8 Gy in 28 fractions to SIB2 (lower/middle third of vagina, paraurethral region and right inguinal lymph nodes). Brachytherapy dose prescription was 28 Gy in 4 fractions for cervix, fundus of uterus and upper third of vagina (HR-CTV1), and 22 Gy in 4 fractions to middle third of vagina and paraurethral region (HR-CTV2). D90 for whole treatment was 91.9 Gy and 86.0 Gy for HR-CTV1 and HR-CTV2, respectively. Patient remained 12-months disease-free without treatment related side effects.