Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: Can One Still Effectively Become a Mother? A Systematic Review of Fertility Outcomes.

BACKGROUND: Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC); however, there is currently no standard of care for women with ECC ≥ 2 cm who wish to preserve their fertility. The current orientation of the scientific community comprises upfront surgical techniques and neoadjuvant chemotherapy (NACT) followed by minor surgery such us conization. However these approaches are not standardized. This systematic review aimed to collect the evidence in the literature regarding the obstetric outcomes of the different techniques for applying FSTs in ECC ≥ 2 cm. METHODS: A systematic review was performed in September 2022 using the Pubmed and Scopus databases, from the date of the first publication. We included all studies containing data regarding pregnancy, birth, and preterm rates. RESULTS: Fifteen studies fulfilled the inclusion criteria, and 352 patients were analyzed regarding fertility outcomes. Surgery-based FST showed the pregnancy rate (22%), birth rate (11%), and preterm rate (10%). Papers regarding FST using the NACT approach showed a pregnancy rate of 44%, with a birth rate of 45% in patients who managed to get pregnant. The preterm rate amounted to 44%, and pregnancy rates and birth rates were significantly different between the two groups (p < 0.001). CONCLUSION: Fertility preservation in patients with ECC > 2 cm is challenging. The endpoint for evaluating the best treatment should include oncological and fertility outcomes together. From this prospective, NACT followed by less radical surgery could be a reasonable compromise.

Endometrial cancer in unicornuate uterus: a case report.

PURPOSE OF INVESTIGATION: Miillerian anomalies have not been implicated as a significant risk factor for the development of cervical, uterine, and ovarian cancers; in the present literature, there are only a few reports of endometrial cancer arising in patients with Miillerian abnormalities. To the best of the authors' knowledge, this is the first reported case of endometrial cancer arising in a patient with unicornuate uterus. CASE REPORT: A 69-year-old Caucasian woman underwent clinical examination and office hysteroscopy with endometrial biopsy because of abnormal post-menopausal bleeding. The diagnosis was endometrial cancer in unicornuate uterus, hence the patient underwent total hysterectomy with pelvic lymphadenectomy. CONCLUSION: Uterine malformations and genetic disorders may cause a delayed diagnosis of gynaecological cancers. Gynaecological examination in asymptomatic patients and differential diagnosis in abnormal uterine bleeding patients should be considered.

Benign pulmonary metastasizing leiomyomatosis: case report.

The authors report a rare case of leiomyomatosis of the lung diagnosed in a 43-year-old woman, with uterine intravenous leiomyomatosis. Benign metastasizing leiomyoma (BML) is an extremely rare lesion characterized by usually multiple, benign-appearing smooth muscle tumors of the lung in females with coexisting uterine leiomyoma. On the basis of their histological and immunohistological features, a unified histogenetic view of leiomyomas with vascular invasion (LWVI) and BML of the uterus is proposed. LWVI and BML may be the same pathological entity and microscopic vascular invasion may represent the metastatic mechanism of BML. LWVI seems to be the precursor of BML.

Cord blood unit bankability can be predicted by prenatal sonographic parameters.

OBJECTIVE: To identify possible sonographic prenatal parameters and postnatal parameters in order to obtain more bankable cord blood units (CBUs) containing a high number of primitive progenitor cells, allowing CBUs to be used as a source of haematopoietic progenitors for clinical transplantation. STUDY DESIGN: Prospective study undertaken in the Department of Gynaecology, Obstetrics and Reproductive Science, Second University of Naples, Italy. In total, 219 unrelated CBU donors were enrolled. Ultrasound parameters (biparietal diameter, head circumference, abdominal circumference, femur length, estimation of fetal weight, umbilical artery pulsatility index), collected at hospital admission, together with birth weight and placental weight, were correlated with bankable CBU parameters (CBU volume, total nucleated cell count, CD34+ cell count). RESULTS: Femur length and abdominal circumference correlated positively with bankable CBUs. Receiver operating curve analysis showed that these parameters can identify bankable CBUs. CONCLUSIONS: This is the first prospective study to show the relationship between ultrasonographic fetal parameters at term and the possibility of obtaining high-quality CBUs. As such, cord blood banking could be improved worldwide by performing low-cost ultrasonographic scans.

[Sonographic aspects in the study of endometrial receptivity in women undergoing in vitro fertilization]. / Aspetti ecografici nello studio della recettività endometriale in donne sottoposte a programmi di fertilizzazione in vitro.

AIM: The embryo implant is the limiting step of the reproductive process about the phenomena involved in the determinism of endometrial receptivity. Some aspects of ultrasound could help us in this regard. The aim of this study was to test the relationship between three ultrasound parameters such as endometrial pattern, subendometrial vascularization, and uterine artery pulsatility index with success rates of in-vitro fertilization (IVF) and with pregnancy rates. METHODS: Twenty-four women candidates for IVF in 2009 were enrolled. A transvaginal ultrasound was performed two-four hours before the embryo transfer to assess differences in the endometrial pattern, subendometrial vascularization, and uterine artery pulsatility index with reference to the group of pregnant and non-pregnant women. RESULTS: Pregnant women most often reveal a trilaminar pattern, a subendometrial vascularization with vessels that penetrate the outer hyperechoic edge of endometrium, and a low-medium uterine artery pulsatility index compared to the group of non-pregnant patients. CONCLUSION: All three studied parameters seem to correlate in the determinism of endometrial receptivity. This leads us to conclude that a trilaminar pattern supported by a correct vascularization and by uterine artery pulsatility index of less than three are good predictors of implant. Their evaluation before subjecting the patient to the embryo transfer may help to increase the pregnancy rate.

Endocannabinoid system in first trimester placenta: low FAAH and high CB1 expression characterize spontaneous miscarriage.

Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were the first endocannabinoids to be characterized, that bind two G protein-coupled receptors, CB1 and CB2. AEA synthesized by multiple pathways, including NAPE-specific phospholipase D (NAPE-PLD) and degraded by the fatty acid amide hydrolase (FAAH). AEA levels are critical in regulating embryo development and the "window" of implantation. We examined the expression of nape-pld mRNA, CB1 and FAAH in human placenta hypothesizing that their altered signaling may contribute to spontaneous miscarriage. First trimester placentas from women with spontaneous miscarriage (group 1) were matched with placentas from women who underwent termination (group 2). Nape-pld expression was analyzed by RT-PCR; CB1 and FAAH expression by Western blot and immunohistochemistry. Nape-pld mRNA expression was higher in group 2 than in group 1. Western blot analysis revealed higher CB1 expression and lower or absent FAAH in group 1 than in group 2. Immunohistochemistry confirmed CB1 and FAAH signals in group 1 and group 2 placentas, respectively. Human placenta contains the enzymes to synthesize AEA. Moreover, placental tissue represents a target for endocannabinoids whose activity may regulate pregnancy outcome. In particular, very low or absent FAAH and high CB1 levels correspond with spontaneous miscarriage.

Therapeutic alternatives in Behçet's syndrome.

Behçet's Syndrome (BD) is a chronic, relapsing, recurrent systemic vasculitis with an unknown cause. The disease affects all organs of the body concurrently or consecutively. Its various clinical manifestations result from ubiquitous small-vessel vasculitis, which is the underlying pathology. An Italian study has reported an increased association of the extended haplotype B51-DR5-DQw3. Without a known etiology BD syndrome has no uniformly acceptable therapy. Our study addresses therapeutic alternatives for the treatment of BD, with the systemic use of interferon alpha-2a., which has antiviral. immunomodulatory, antiproliferative, and antitumoral properties. Ten patients diagnosed with BD were referred from September 2002 to September 2005 to the Department of Gynaecology, Obstetrics and Reproduction of the Second University of Naples. The International Study Group (ISG) Criteria for Behçet's Disease (27) was applied. Patients were treated with oral prednisone; sulfasalazine; clobetasol; and interferon alpha-2a. Every month all patients had a complete blood count, platelet count, and liver function test. Biopsies of genital ulcerations identified small vessel vasculitis with mononuclear cell and lynphocytic infiltrates. HLA-B27 and B5 were positive in three subjects. The pathergy test was positive in all patients. Today the therapy is still ongoing, and none of the patients in therapy with our protocol present clinical symptoms of BD or intolerance. Laboratory findings are in a normal range and none have had neurological failure. Our findings may be attributable to less severe disease in a patients, to our smaller number of patients, or to other unknown factors. Nonetheless, these findings remain to be confirmed in a larger number of patients.

A rare case of female pelvic mass: angioleiomyoma of the broad ligament.

Angioleiomyoma is a benign mesenchymal neoplasm composed of smooth muscle cells and thick-walled vessels. It is usually found in the skin of the lower extremities. Angioleiomyoma is a very rare tumor among the ever-expanding repertoire of growth variants described in benign uterine leiomyoma. More rare is a solitary tumor of the broad ligament. Thus angioleiomyoma of the broad ligament is an extremely rare benign tumor of the female pelvis. In this report a 52-year-old woman with a one-year history of abdominal pain was admitted to our hospital. Gynaecological and ultrasonography exams showed a large mass with increased vascularization in the right adnexal region. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy. The site of the benign mass was the left broad ligament of the uterus. On pathologic examination of the specimen, the tumor was diagnosed as angioleiomyoma. We present a case of angioleiomyoma of the broad ligament because of its extreme rarity and the large size of the tumor.

Low-dose hormone therapy in the perimenopause.

OBJECTIVE: To evaluate the effects of low-dose hormone therapy (LD-HT) on bleeding pattern and vasomotor symptoms in perimenopausal women. METHODS: In a prospective, open-label study at an University clinic, 120 perimenopausal women suffering from irregular menstrual cycles and hot flushes were randomized to micronized 17beta-estradiol 1 mg plus dydrogesterone 10 mg sequential added (LD-HT; group A: 60 subjects) or dydrogesterone 10 mg from day 15 to 28 (group B: 60 subjects). Number and severity of hot flushes and bleeding pattern were assessed throughout the study. RESULTS: Women in group A experienced a significant reduction in number of hot flushes while no significant variation was observed in group B. The incidence of cyclic bleeding was 86% in group A and 76% in group B, the mean duration was significantly lower in group A than in group B. CONCLUSIONS: LD-HT may control both irregular bleeding and hot flushes in perimenopausal women.

Association of body weight with sexual function in women.

Sexual difficulties in women appear to be widespread in society; the relationship between female sexual function and obesity is unclear. This study aimed to investigate the relationship between body weight, the distribution of body fat and sexual function in women. Fifty-two, otherwise healthy women with abnormal values of female sexual function index (FSFI) score (< or =23) were compared with 66 control women (FSFI >23), matched for age and menopausal status. All women were free from diseases known to affect sexual function. FSFI strongly correlated with body mass index (BMI) (r=-0.72, P=0.0001), but not with waist-to-hip ratio (r=-0.09, P=0.48), in women with sexual dysfunction. Of the six sexual function parameters, desire and pain did not correlate with BMI, while arousal (r=-0.75), lubrication (r=-0.66), orgasm (r=-0.56) and satisfaction (r=-0.56, all P<0.001) did. FSFI score was significantly lower in overweight women as compared with normal weight women, while cholesterol and triglyceride levels were higher. On multivariate analysis, both age and BMI explained about 68% of FSFI variance, with a primacy of BMI over age (ratio 4:1). In conclusion, obesity affects several aspects of sexuality in otherwise healthy women with sexual dysfunction.

Modulation of apelin and APJ receptor in normal and preeclampsia-complicated placentas.

Apelin is an endogenous ligand of the human orphan receptor APJ. This peptide is produced through processing from the C-terminal portion in the pre-pro-protein consisting of 77 amino acid residues and exists in multiple molecular forms. Although the main physiological functions of apelin have not yet been clarified, it is known that apelin is involved in the regulation of blood pressure, blood flow and central control of body fluid homeostasis in different organs. Since human placenta is a tissue where vasculogenesis, blood pressure and flow are dramatically important to allow a normal embryonic and fetal growth and development, the aim of the present study was to investigate the immunohistochemical distribution of apelin and APJ in normal placentas throughout pregnancy and in preeclampsia-complicated placentas. Specifically, we observed that in normal placentas the expression levels of apelin decreased from the first to the third trimester of gestation in both cytotrophoblast and syncytiotrophoblast cells and in the stroma of placental villi, in contrast with increased expression levels of APJ in the cytoplasm of cytotrophoblast cells and in the cytoplasm of endothelial cells of normal placenta samples. In contrast, in preeclampsia-complicated pregnancies, we observed a very strong increase of expression levels of both apelin and APJ receptor in all the placental compartments, cytotrophoblast, syncytiotrophoblast and stroma with a particular increase in endothelial cells inside preeclamptic placental villi. Our data seem to indicate an important role of apelin and APJ in the regulation of fetal development through a correct regulation of human placenta formation during pregnancy. Moreover, the strong expression levels of apelin and APJ in preeclamptic placentas, suggest their possible involvement in the onset of this pathology.

Expression and distribution of notch protein members in human placenta throughout pregnancy.

Notch signaling is an evolutionarily conserved mechanism used by invertebrates and vertebrates to control cell fates through close-range cell interactions. Four Notch receptors have been identified in vertebrates and different ligands, divided into Delta-like and Serrate-like (Jagged). Several studies have demonstrated that Notch signaling is involved in different branches of the cell fate decision tree: differentiation, proliferation and apoptosis. These three processes are finely regulated in human placenta in order to allow a successful pregnancy and a correct fetal growth. Moreover, Notch and its ligands participate in the vascular remodelling and stabilization, other two processes much important and ticklish in human placenta. So, we decided to investigate the pattern of expression of Notch-1, Notch-4 and Jagged-1, together with two members related to Notch pathway and involved in angiogenesis: VEGF and p21, in human placenta during gestation by immunoblotting and immunohistochemistry. We showed a modulation of Notch proteins throughout the pregnancy; in particular we showed a slight decrease of Notch-1 throughout pregnancy, with a decreased cytoplasmic staining from the first to the third trimester of gestation in cytotrophoblast and syncytiotrophoblast. In contrast Jagged-1 showed an increase throughout pregnancy especially in syncytiotrophoblast and stroma during the third trimester of gestation. In addition, we found by immunoblotting an increase of VEGF expression from the first to the third trimester and an intense VEGF expression inside endothelial cells throughout the gestation as also confirmed by immunohistochemistry. We also showed a decrease of p21 expression during the pregnancy both through immunoblotting and immunohistochemistry assays. Moreover, we observed Notch localization in extravillous trophoblast cells that are able to invade the decidualized endometrium. Our results suggest an involvement of Notch signaling in regulation of placental cell fate decision and in angiogenesis that are dramatically important to maintain a normal physiology of this organ during pregnancy.

The rectal pocket syndrome after stapled mucosectomy.

OBJECTIVE: Stapled rectal mucosectomy (SM) is less painful than manual haemorrhoidectomy but may be followed by unusual complications which may require reinterventions. The aim of the present study was to report on a particular postoperative complication, the rectal pocket syndrome (RPS). METHODS: Six patients, four females and two males, five with severe proctalgia and signs of intermittent sepsis and one with faecal soiling following SM, underwent clinical examination, proctoscopy (n = 5) anal manometry and ultrasound (n = 4) revealing a painful rectal intramucosal pocket with an endoluminal orifice at the level of the suture line. Four of them underwent a reintervention. RESULTS: At surgery, a faecolyth was found to be entrapped in the rectal pocket with an underlying chronic abscess in four patients. The cavity was laid open and curetted in all cases. One of the females needed a fistulotomy of a low intersphincteric track after one year. In none of the others did endorectal pocketing and abscess or prostatitis recur after a mean follow up of 25 months (range 2-60 months). The male patient still had moderate postevacuation pain and prostatitis possibly via a bacterial translocation after two months. Overall, the incidence of the post mucosectomy RPS at our Units was 2.5%. CONCLUSIONS: The RPS can occur after SM, is likely to be due to a failure of either the purse-string or of the staples causing a suture defect leading to an intramural sinus, and may be successfully treated by a transanal lay-open in most cases.

A therapeutic algorithm for early-stage endometrial cancer: indications, patient selection, and feasibility.

Endometrial cancer is the most widely spread gynaecologic neoplasm in industrial countries. Mode of spread includes direct extension, lymphatic and haematic diffusion. Lymphatic involvement, particularly, is a topic of wide debate due to the strong therapeutic implications associated with it. In this regard, anatomic-surgical staging is better in that it corresponds to real conditions whereas clinical-instrumental staging is still today incomplete.

[Fetal and maternal amniocentesis complications]. / Complicanze materno fetali dell'amniocentesi.

AIM: The aim of this study was to estimate the incidence of complications due to the prenatal invasive diagnosis performed by amniocentesis at the Department of Prenatal Diagnosis of the Second University of Naples. METHODS: A total of 1.580 patients who underwent amniocentesis from January 2001 to December 2003, were submitted to a telephone interview concerning the complications that occurred after the invasive diagnosis. RESULTS: Only 1.416 patients out of the total patients interviewed answered correctly to the questionnaire. The complications that occurred in the first 24 h from amniocentesis (early complications) included light contractions and lipothymia respectively in 8.3% and 6.7% of cases; losses of amniotic fluid took place in 1.06% while bleedings were observed in 0.85% of cases. The incidence of abortions occurred in the week following amniocentesis was 0.78%. Preterm labor occurred in only 6% of the patients submitted to amniocentesis, spontaneous labor at term in 43% and cesarean section in 51%. The Apgar index at birth was normal in 95.7% of cases. In the remaining 4.3% pathologies like hypoglycemia or respiratory distress, which promptly regressed, were observed. Early complications and the incidence of abortions were significantly and independently associated with the double needle puncture but not with maternal age or the placenta specimen obtained during amniocentesis. CONCLUSIONS: A careful observation of the technique and the protocol, as well as a careful selection of patients are necessary presuppositions in order to further decrease the occurrence of complications due to amniocentesis.

Third stage ovarian carcinoma--case report: the necessity of a multidisciplinary approach to treatment.

Ovarian carcinoma, part of a heterogeneous group of tumours, is the main cause of death by gynaecological neoplasms. The diagnosis, in general, is delayed. Multiorgan diffusion, the necessity of a surgical operation and strong chemotherapy, and the eventual pathology due to patient age are all factors that require a multidisciplinary approach. In fact the case, here reported, refers to a patient who came under our observation for a bilateral ovarian mass discovered casually during an abdominal ultrasound exam carried out for renal colic. Excellent cytoreduction with peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy (Figure 2), bilateral pelvic lymphadenectomy, total omentectomy, removal of nodules from the mesentery, the colon and three nodules in the abdominal wall thickness was executed. The histological report was G3, angioinvasive bilateral ovarian endometrioid adenocarcinoma. Metastasis was found only in one left obturator lymph node out of 17 lymph nodes removed. All of the removed abdominal, mesenteric and intestinal nodules were neoplastic. It is concluded that the complexity of similar cases always requires a multidisciplinary approach as in our case, involving an oncologist, hematologist, surgeon, gynaecologist, radiologist, anaesthesiologist, and nursing staff in the management of third stage ovarian cancer patients to obtain the best treatment thus guaranteeing a higher survival rate and better quality of life.

[A fetal soft marker in obstetric ultrasonography: single umbilical artery]. / Un fetal soft marker nell' ultrasonografia ostetrica: l'arteria ombelicale unica.

The recent advancement in the field of ultrasonography allows for the prenatal precocious diagnosis of an ever increasing number of congenital defects found in various areas of the foetal body. These phenotype variants (markers) and/or morphological anomalies reveal in the majority of cases of a foetus with chromosome defects. They represent ''alarm bells'' that intrigue us to uncover any average case with more tests. It is for this that many more efforts are made to identify echographical markers which allow us to select among the pregnant women those that are not at risk and to advise those that may be of the existence of a specific cytogenetic test. One of these markers is actually represented by the single umbilical artery. This anomaly is made up of the presence of only two vessels (an artery and a vein) at the level of the umbilical cord, and its lack of an artery. The clinical meaning of this pathology is not yet completely known today. Often, in fact, when isolated, it is not associated with a chromosome defect and to other foetal pathologies. When, however, it is presented as associated to other soft markers or other structural anomalies, the risk of a chromosome defect is notably higher.

Apoptosis and human placenta: expression of proteins belonging to different apoptotic pathways during pregnancy.

Apoptosis occurs during normal development and it is important for the right balance between the loss of old, non-functional cells and the formation of new cells in different organs and tissues. Apoptosis is triggered by different cell-type-specific signals which involve several pathways, such as mitochondrial and receptor-mediated pathways, resulting in caspase cascade activation. Several studies have suggested that apoptosis plays an important role in the normal development, remodelling and aging of the placenta. Moreover, it has been demonstrated that apoptosis increases as pregnancy progresses suggesting that it is a normal physiological phenomenon throughout gestation. In the last years, it has been hypothesized that the process known as syncytial fusion is directly or indirectly related to apoptotic events. In particular, it has been suggested that cytotrophoblast cells early express most important apoptotic proteins that translocate in the syncytiotrophoblast with the fusion. This suggests that apoptosis has a central role in the villous trophoblast turnover. Recently, another important involvement of apoptotic processes in human placenta has been demonstrated. In particular, the apoptosis, mainly through Fas-FasL or TRAIL-R-TRAIL signalling, may be a defence mechanism against rejection of the fetal allograft by maternal immune system. The whole data suggest that regulation of apoptotic events is important to allow a correct development, differentiation and function of the placenta throughout pregnancy and that an unbalance of this process leads to severe pathologies such as pre-eclampsia and intrauterine growth retardation. Therefore, due to its extensive proliferation and invasive properties, the placenta mimics a malignant tumor and represents an interesting model to evaluate those processes leading to carcinogenesis.

Management of poor responders in IVF.

Correct controlled ovarian stimulation is of paramount importance in assisted reproductive technologies. Therefore, analysis of the ovarian reserve of the patient is mandatory to tailor the best ovarian stimulation regimen. When the ovarian reserve is reduced, the induction of a multifollicular growth remains a challenge. Several factors could be associated with reduced ovarian response. However, reduced ovarian reserve either in older patients or in young patients represents the most frequent aetiological factor. Whatever is the aetiology, one of the main problems is how to predict a reduced ovarian response, and although several tests have been suggested, no very accurate predictive test is available. A variety of different stimulation protocols have been suggested but the lack of any large-scale, prospective, randomized, controlled trials of the different management strategies and the lack of a uniform definition of the population may result in comparisons of heterogeneous groups of patients, making it difficult to draw any definitive conclusions. Natural cycle IVF may represent an easy and cheap approach in the management of this group of patients. Although no controlled large prospective randomized studies are available to compare the natural IVF procedure with ovarian stimulation IVF in poor responder patients, the efficacy of natural cycle IVF is hampered by high cancellation rates mainly due to untimely LH surge. The use of gonadotrophin-releasing hormone antagonists in the late follicular phase, which reduces the premature LH rise rate, and the improvements in laboratory conditions and fertilization techniques, increase the embryo transfer rates, making this procedure more cost-effective.