CO2 laser colposcopic guided surgery for the see and treat management of VHSIL: a preliminary experience.

The purpose of this study is to evaluate the efficiency of CO2 laser colposcopic guided surgery performed in an outpatient see and treat setting in the management of VHSIL. Women with a suspected diagnosis of VHSIL and no vulvoscopic suspicion of vSCC were enrolled. An electronic register of CO2 laser treatment was created where description of performing parameters (excision or ablation) was specified and personal history was recorded. Statistical analysis was performed by Fisher's exact test. Relative risks (RR) of risk factor were calculated and expressed in odds. From September 2014 to September 2018, we enrolled a total of 63 patients who underwent CO2 laser procedure and had a minimum follow-up time of 2 years at Careggi University Hospital in Florence. Forty-eight (76.2%) patients underwent laser excision and 15 (23.8%) patients underwent ablative treatment without histological results. Undertreatment was performed in 3 cases (6.3%) with definitive histology of vSCC. Therapeutical appropriateness of CO2 laser excision was reached in 85.4% of the cases (41/48). No volunteer loss to follow-up was registered; thus, fidelity to treatment was assess at 100%. Recurrence rate within 2 years attested in 8/60 followed patients (13.3%). No personal factor was found to influence the VHSIL course. CO2 laser excision may represent an excellent therapeutic option to VHSIL because it provides adequate oncological purpose with good cosmetic and functional results and high patients' loyalty to treatment. An expert team could allow to undergo patients with VHSIL suspicion to unique diagnostic and therapeutic procedure with significant benefits.

Colposcopic patterns of vaginal intraepithelial neoplasia: a focus on low-grade lesions.

OBJECTIVE: The aim of this study was to evaluate the colposcopic patterns observed in women with a histopathological diagnosis of vaginal intraepithelial neoplasia, with a particular interest in analyzing the colposcopic characteristics of low-grade squamous intraepithelial lesions (LSIL). PATIENTS AND METHODS: Medical charts and colposcopy records of women diagnosed with vaginal intraepithelial neoplasia from January 1995 to December 2015, were analyzed in a multicenter retrospective case series. The abnormal colposcopic patterns observed in women with vaginal LSIL and vaginal high-grade SIL (HSIL) were compared. The vascular patterns and micropapillary pattern were considered separately. RESULTS: Regardless the histopathological grading, in women with vaginal SIL, the grade I abnormal colposcopic findings were more frequent than grade II abnormalities. However, a grade I colposcopy was more commonly observed in women with a biopsy diagnosis of LSIL rather than HSIL (p<0.0001). Similarly, the micropapillary pattern was more frequently observed in women with LSIL (p=0.004), while vascular patterns were observed more frequently in women diagnosed with vaginal HSIL (p<0.0001). In women with grade I colposcopy, the menopausal status and a previous hysterectomy appeared to be associated with the diagnosis of vaginal HSIL. CONCLUSIONS: Grade I abnormal colposcopic findings were more commonly observed in women with vaginal LSIL, as well as the micropapillary pattern. On the other hand, grade II abnormal colposcopy and the presence of vascular patterns were more frequently observed in women with vaginal HSIL.

High-grade vaginal intraepithelial neoplasia and risk of progression to vaginal cancer: a multicentre study of the Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV).

OBJECTIVE: The aim of this study was to analyse the women with high grade vaginal intraepithelial neoplasia (HG-VaIN), in order to identify a subset of women at higher risk of progression to invasive vaginal cancer. MATERIALS AND METHODS: The medical records of all the women diagnosed with HG-VaIN, and subsequently treated, from January 1995 to December 2013 were analyzed in a multicentre retrospective case series. The rate of progression to invasive vaginal cancer and the potential risk factors were evaluated. RESULTS: 205 women with biopsy diagnosis of HG-VaIN were considered, with a mean follow up of 57 months (range 4-254 months). 12 cases of progression to vaginal squamocellular cancer were observed (5.8%), with a mean time interval from treatment to progression of 54.6 months (range 4-146 months). The rate of progression was significantly higher in women diagnosed with VaIN3 compared with VaIN2 (15.4% vs. 1.4%, p < 0.0001). Women with HG-VaIN and with previous hysterectomy showed a significantly higher rate of progression to invasive vaginal cancer compared to non-hysterectomised women (16.7% vs. 1.4%, p < 0.0001). A higher risk of progression for women with VaIN3 and for women with previous hysterectomy for cervical HPV-related disease was confirmed by multivariable logistic regression analysis. CONCLUSIONS: A higher rate of progression to vaginal cancer was reported in women diagnosed with VaIN3 on biopsy and in women with previous hysterectomy for HPV-related cervical disease. These patients should be considered at higher risk, thus a long lasting and accurate follow up is recommended.

Spontaneous regression of low-grade cervical intraepithelial lesions is positively improved by topical bovine colostrum preparations (GINEDIE®). A multicentre, observational, italian pilot study.

OBJECTIVES: Human papillomavirus (HPV) is the causal agent of cervical cancer. The great majority of abnormal Pap test results - almost 90% - is referrable to either atypical squamous intraepithelial lesion or CIN1. For these lesions, worldwide agreement exists concerning the high rate - ranging from 40% to 70% - of spontaneous regression over a period of 1-5 years. Host's immune response is a key point influencing the natural history of these conditions. Bovine colostrum is a natural agent positively promoting several immune activities against bacterial and viral agents. The aim of this report was to evaluate the potential positive effect of bovine colostrum-containing vaginal tablets administered to CIN1 diagnosed patients in a prospective trial in regards to spontaneous regression rate. PATIENTS AND METHODS: A series of 256 consecutive patients with histologically proven CIN1 recruited in a multicentre, observational, Italian study. Patients have been enrolled in a 24-weeks protocol of treatment and re-tested at the end of the study. Rates of regression have been recorded. RESULTS: Overall regression rate to a negative histology at the end of the 6 month follow up was 75.5%. CONCLUSIONS: Regression to normal histology was observed in a very high rate of cases in a very short period compared to the natural history of these lesions. CIN1 patients could benefit from bovine colostrum topical administration in terms of significantly shortening the regression time.

Methylation of the HOXA10 homeobox gene promoter is associated with endometrial cancer: a pilot study.

Methylation in the promoter region represents an epigenetic mechanism that silences expression of various homeobox genes in cancers. We compare the methylation profile of HOXA10 promoter gene in 19 histologically proven endometrioid cancers and 27 normal endometrial tissues. Endometrial cancer tissue displays significantly higher methylation status in HOXA10 gene promoter than normal tissue, suggesting a possible role of epigenetic changes in HOXA10 gene regulation in tumorigenesis. Further studies in human tissue and cell lines are necessary to validate these preliminary results and to investigate HOXA10 expression according to methylation status in endometrial cancer.

Stillbirth and fetal growth restriction.

OBJECTIVE: To confirm the role of fetal growth restriction (FGR) as a cause of stillbirth, and to compare diagnostic accuracy of customized fetal growth and population-based standards in identifying FGR within a pathological population of early and late stillbirths. METHODS: Retrospective study on a cohort of 189 stillbirths occurred in single pregnancy between January 2006 and September 2011. Unexplained stillbirths, defined by Aberdeen-Wigglesworth and ReCoDe classifications, were evaluated on the basis of fetal birthweight with both Tuscany population and Gardosi customized standards. Unexplained stillbirths have been classified as early or late depending on the gestational age of occurrence. RESULTS: Aberdeen-Wigglesworth classification, applied to the 189 cases of stillbirth, left 94 unexplained cases (49.7%), whereas the ReCoDe classification left only 40 (21%). By applying population standards to the 94 unexplained stillbirths we have identified 31 FGRs (33% of sample), while customized standards identified 54 FGRs (57%). Customised standards identified a larger number of FGRs with respect to population standards during the third trimester (i.e. 51% vs. 25% respectively) than in the second trimester (73% vs. 54% respectively) (p = 0.05). CONCLUSIONS: Customized standards have a higher diagnostic accuracy in identifying FGRs especially during the third trimester.

OS086. Methylation status of the HOXA13 promoter region in placental tissue of pregnancies complicated by early onset severe preeclampsia.

INTRODUCTION: Compromised placental function and morphology found in early onset preeclampsia as well as a modified phenotype of the fetus may derive from a deviation in the normal gene expression pattern. Previous studies demonstrated by experimental animal models, that the gene HOXA13 plays an essential role in the arrangement of the placental vascular net, identifying direct and indirect target functions this gene has on the endothelial component. Research in model systems and now expanding to human studies has suggested that the causes and consequences of a variety of pregnancy-related pathologies are connected to epigenetic regulation. OBJECTIVES: To evaluate the methylation status of the promoter region of HOXA13 within placental tissue and its association with specific clinical signs of severe early onset preeclampsia. METHODS: A prospective case - control study was performed to evaluate the methylation status of the promoter region of HOXA13 by pyrosequencing analysis within placental tissue and its association with specific clinical signs of severe early onset preeclampsia (EOSP). RESULTS: The group of preeclamptic patients reached a mean methylation degree of 27.06% (±8.94) and 30.56% (±8.08) on two CpG islands of HOXA13 5' promoter respectively. Conversely in the group of physiologic controls the mean degree of methylation resulted 15.12%(±3.64) (p<0.0016) and 18.25% (±3.45) (p<0.0005). CONCLUSION: This study firstly demonstrated that an hypermethylation of placental HOXA13 exists in preeclamptic placental tissues and concentrates only on the gene promoter. Additionally, the existence of a correspondence between themethylation process of the gene promoter HOXA 13 and the clinical manifestation of severe early onset preeclampsia supports the original hypothesis that this process may be at the base of the preeclamptic pathogenesis.

[Tamoxifen, endometrial cancer risk and liquid based cytology. A paradigmatic case]. / Tamoxifene, rischio oncologico endometriale e citologia in fase liquida. Un caso clinico paradigmatico.

Long-term users of tamoxifen (TMX) are at increased risk for developing endometrial cancer. Early diagnosis is mainly based on transvaginal scan (TVS) and hysteroscopy with endometrial biopsy. Nevertheless, TVS does not provide a definitive diagnosis in most cases, particularly due to its high false-positive rate. In addition TMX related changes, such as "pseudocistic" pattern, affect endoscopic evaluation of the endometrium and biopsy sampling (in particular blind procedures) frequently yields insufficient tissue for diagnosis. The cause of the high inadequacy rate of endometrial biopsies in women on TMX might be related to the increase in endometrial fibrous component. The present case emphasizes the main difficulties in surveillance and early diagnosis of endometrial pathologies in TMX users. Liquid-based endometrial cytology played a determinant role in the diagnostic pathway of this patient. We believe it could be used solely or in association with TVS leading to many advantages in the surveillance of women receiving TMX.

Comparison of the number of uterine myomas detected by in-office transvaginal ultrasonography removed by laparotomic myomectomy: preoperative work-up concerns.

PURPOSE OF INVESTIGATION: To assess the ability of detecting the number of uterine myomas by transvaginal ultrasonography (TVS) performed supporting the clinical examination of general gynecologists' office practice. METHODS: A retrospective comparison of the number of myomas revealed by preoperative in-office TVS and documented after laparotomic myomectomy was conducted in 110 consecutive premenopausal patients referred for surgery. RESULTS: The sensitivity of TVS in revealing the exact number of myomas was 59.4% in the whole series. In the subgroup of 88 patients with a preoperative diagnosis of three or fewer myomas TVS missed at least one myoma in 31 (35.2%) cases, achieving a 64.8% sensitivity. Among the 72 women diagnosed with one myoma at preoperative TVS, 19 (26.4%) resulted to have two or more myomas at the end of surgery, reaching a 73.6% sensitivity of TVS in revealing the exact number of myomas. CONCLUSIONS: In-office TVS reinforces the clinical diagnosis of uterine myomas but it often fails in the detection of their number, resulting in a poor preoperative characterization of patients. The fact that one myoma may be overlooked in one-third of patients theoretically eligible for laparoscopic conservative surgery may motivate the implementation of US diagnosis when laparoscopic myomectomy is considered.

Pregnancy outcome in systemic lupus erythematosus complicated by anti-phospholipid antibodies.

OBJECTIVE: Pregnant women affected by SLE are at high risk of gestational hypertension and pre-eclampsia (32-50%). This risk is particularly elevated if aPLs are dosable. The present study was planned to evaluate maternal-fetal outcomes of different groups of SLE pregnant patients characterized by diverse risk factors: patients affected by APS treated with a combination of low-dose aspirin (LDA) and low-molecular weight heparin (LMWH), nulliparous patients with dosable aPL treated by LMWH and SLE patients with no aPL administered no treatment during pregnancy. METHODS: A retrospective description of maternal and fetal outcomes was made in a total of 62 pregnancies presenting APS in 8 cases (12.9%), aPL in 20 (32.2%) and no aPL in 34 (54.8%). RESULTS: No statistically significant difference was found comparing fetal and maternal outcomes of the three groups despite differences in SLE activity: SLE aPL-positive pregnancies were associated with a higher incidence of nephritis and chronic hypertension than pregnancies treated for APS or not presenting with the added risk factor. The incidence of pre-eclampsia is 15% in aPL positive, 12.5% in APS and 14.7% in no aPL pregnancies, respectively. CONCLUSIONS: LMWH is rather a possible option of prophylaxis for SLE aPL-positive pregnancies with potential maternal-fetal outcomes similar to aPL-negative patients or to standard treated APS.

Prognostic significance of high-risk HPV persistence after laser CO2 conization for high-grade CIN: a prospective clinical study.

PURPOSE OF INVESTIGATION: To estimate the persistence rate of high-risk HPV DNA (HR-HPV DNA) in a population treated totally by laser CO2 conization for high-grade cervical intraepithelial neoplasia (HG-CIN), and to examine if this persistence might be considered an independent risk factor for relapsing disease. METHODS: All women with a histological diagnosis of HG-CIN and planned for laser CO2 conization from January 2003 to December 2004 were prospectively submitted to a HR-HPV test prior to surgery and at three and six months of follow-up. Women providing written informed consent with 24 months of follow-up were enrolled in the study group. A positive HPV test, involvement of resection margins, age at first intercourse, smoking habits, parity and age at conization > 50 years old were considered as risk factors for relapsing HG-CIN during follow-up, and were univariately and multivariately analyzed to discover any independent influencing factors. RESULTS: Of HG-CIN 15.4% resulted not to be HPV related nor relapsing. The HPV clearance rate after treatment was 78.8%. Involvement of resection margins and HR-HPV DNA persistence post-treatment resulted as the only two statistically significant risk factors for HG-CIN recurrence (rate 3.8%). HR-HPV DNA persistence in follow-up resulted to be independent from other risk factors at multivariate analysis. CONCLUSIONS: Although able to reach a low recurrence rate of HG-CIN, laser CO2 conization does not remove HPV infection completely from the cervix with a case of persistence in every five treated patients. In our experience this persistence in itself represents an independent risk factor for developing relapsing disease and constitutes the basis to introduce HPV testing even in the follow-up of patients treated for HG-CIN by laser CO2 conization.

Clinical utility of liquid-based cytology for the characterization and management of endometrial polyps in postmenopausal age.

The proper management of endometrial polyps still represents a clinical ongoing challenge, especially when they are asymptomatic and occasionally discovered. The aim of this study was to evaluate liquid-based endometrial cytology to manage endometrial polyps in postmenopausal age by its ability to exclude hidden premalignant and malignant changes within polyps. Three hundred fifty-nine consecutive postmenopausal patients who underwent hysteroscopic diagnosis of endometrial polyp over a 3-year period and who were scheduled for surgical removal within the three subsequent months were retrospectively evaluated. Histologic results after resection during operative hysteroscopy or during hysterectomy were compared with liquid-based cytology and endometrial biopsy obtained at the time of diagnostic hysteroscopy. Eight of 359 patients (2.2%) had malignant or premalignant polyps interpreted as benign finding at hysteroscopy. Unsatisfactory samples were higher for endometrial biopsy compared to liquid-based cytology in the whole series and in the subgroup of low-risk asymptomatic patients (P < 0.001). Endometrial biopsy and liquid-based cytology revealed a sensitivity of 62% and 87.5%, respectively and a 100% specificity. Considering the subgroup of low-risk asymptomatic patients, liquid-based cytology disclosed all the five pathologic lesions with a 100% sensitivity and specificity. In conclusion, liquid-based cytology proved to be a useful tool to establish the nature of endometrial polyps in postmenopausal patients. Complete removal of the lesion should be offered to all symptomatic patients and those with established risk factors for endometrial cancer. Conversely, a wait and see attitude should be considered in case of asymptomatic low-risk polyps with typical appearance on hysteroscopy and negative liquid-based cytology.

Feasibility and outcome of laser CO2 conization performed within the 18th week of gestation.

The purpose of this study is to evaluate the feasibility, safety, and potential therapeutic benefit of laser CO(2) conization of the cervix for in situ and minimally invasive carcinoma diagnosed during pregnancy. Twenty-six pregnant patients with biopsy-proven carcinoma in situ/cervical intraepithelial neoplasia III but colposcopically suspicious for invasion underwent laser CO(2) conization during the 18th week of gestation in an outpatient setting under local anesthesia. No major intraoperative or postoperative complications occurred, and cervical cerclage was not required in any case. Two cases (7.7%) of occult FIGO stage IA1 minimally invasive cervical cancers with free surgical margins were diagnosed. Both patients delivered vaginally at term and were free of disease at postpartum follow-up. Median length of gestation was 39.1 weeks with a median birth weight of 3450 g. All 1-min Apgar scores were 8 or greater. Twenty patients (76.9%) delivered vaginally, while six patients underwent cesarean section for indications not related to the prior conization. After a mean postpartum follow-up of 18 months (range 3-42), 92.3% of patients continued to have both cytologic and colposcopic evaluations negative for persistent or recurrent disease. Two cases of persistent intraepithelial disease were successfully managed by reconization. In summary, our data suggest that laser CO(2) conization performed within the 18th week of gestation is safe for both the patient and the fetus, provides reliable histologic diagnosis, and can be curative. Further studies are required to confirm the favorable risk-benefit ratio of laser CO(2) conization in the management of non-reassuring cervical lesions observed in the first half of pregnancy.