Colposcopic patterns of vaginal intraepithelial neoplasia: a study from the Italian Society of Colposcopy and Cervico-Vaginal Pathology.

The aim of this study was to evaluate the colposcopic patterns observed in women with a histopathological diagnosis of vaginal intraepithelial neoplasia (VaIN). The medical charts and the colposcopy records of women diagnosed with VaIN from January 1995 to December 2013 were analysed in a multicentre retrospective case series. The abnormal colposcopic patterns observed in women with VaIN1, VaIN2 and VaIN3 were compared. The vascular patterns and micropapillary pattern were considered separately. A grade II abnormal colposcopic pattern was more commonly observed in women with a biopsy diagnosis of VaIN3 rather than with VaIN1 or VaIN2 (P<0.001). Vascular patterns were also more common in women with VaIN3 rather than with VaIN1 or VaIN2 (P<0.001). Moreover, in women with grade I colposcopy, the rate of VaIN3 was significantly higher when a vascular pattern was observed (62.5 vs. 37.5%; P=0.04). The micropapillary pattern was more common in women with grade I colposcopy and it was more frequently observed in women with VaIN1 rather than in those with VaIN2 or VaIN3 (P<0.001). Grade II abnormal colposcopic pattern was more commonly observed in women with VaIN3. Moreover, the detection of vascular patterns appeared to be associated with more severe disease (VaIN3) even in women with grade I colposcopy, whereas the micropapillary pattern should be considered an expression of a less severe disease (VaIN1 and VaIN2).

Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression.

To date, there are evidence-based guidelines available for cervical dysplasia diagnosed in pregnancy. Certain functional biomarkers have proven useful in the prediction of regressing and non-regressing cervical intraepithelial neoplasia (CIN) lesions in non-pregnant women. In the present study, Ki-67 and p16 immunostaining were evaluated in different grades of CIN lesions diagnosed in pregnant or non-pregnant women with the aim to identify any differences in order to better understand the behavior of CIN in pregnancy. The current retrospective case-control study included 17 pregnant patients that conceived naturally with first-time onset of CIN occurring at no later than 16 gestational weeks. The control group included 17 non-pregnant patients matched for age, parity and number of previous sexual partners. Exclusion criteria included previous cervical treatment, immunocompromised status, chronic hepatitis B and/or C and cigarette smoking. p16 and Ki-67 protein expression were respectively detected using the CINtec Histology kit and monoclonal antibodies against Ki-67. p16 and Ki-67 staining were analyzed using a classification system based on the distribution of positivity on a semi-quantitative three point-scale. p16 and Ki-67 immune reactivity correlated positively with the grade of epithelial dysplasia in the total cohort of pregnant and non-pregnant patients; expression increased linearly from CIN1 to CIN3. Furthermore, the association between p16 immunostaining and CIN grade was significant in non-pregnant patients but not in pregnant patients. In pregnant patients, positivity for Ki-67 was less intense than in non-pregnant patients. These results appear to suggest that pregnancy status interferes with the expression of cellular proteins involved in cell-cycle regulation and the carcinogenic process induced by high-risk human papilloma virus, exhibiting increased variability in their staining.

Procedures of cervical conization: a national survey among Italian colposcopy units.

BACKGROUND: The recent evolution of surgical techniques, anesthesia and treatment strategies has led to a decrease in the number of cervical conization procedures performed in ordinary hospitalization or with anesthetics other than local infiltration anesthesia of the cervix. Conization should be as least invasive as possible, favor women's compliance and resumption of normal daily activities after surgery. We evaluated various aspects of patient care revolving around conization (technical, healthcare, and administrative aspects) in the clinical practice of 26 Italian colposcopy units. METHODS: A standard multiple-choice questionnaire was used. The retrospective study covered a period of 10 years. RESULTS: The overall number of conization procedures performed over the 10 years' observation period ranged from 20,000 to 37,500. The techniques used were the loop electrosurgical excision procedure in 79.9% of cases, CO2 laser in 16.7%, and the cold-knife biopsy in 3.4%. An outpatient regimen was reported in 62.1% of cases, a day-surgery regimen in 35.2% and an ordinary hospitalization in 2.7%. Local anesthesia, deep sedation and general anesthesia were usually performed in 86.7%, 11.9% and in 1.4% of cases, respectively. The use of prophylactic antibiotics was common only in 8% of cases. The rate of major adverse events recorded over the observed period varied between 0.04% and 0.02% (15,000-29,000 conizations). CONCLUSIONS: The administrative regimen in which conizations are performed is an expression of behaviors of different health authorities and hospitals in relation to the costs that this procedure entails.

Management of pathological femoral fracture secondary to breast cancer in pregnancy: A case report.

Bone metastasis resulting from breast cancer in pregnancy is rare. In the literature there are few reports regarding osteolytic lesions in pregnancy and no data on the treatment of such femoral fractures. The present study reports a case of a 29-week primigravida presenting with severe lumbosciatica in the left side, refractory to medical therapy. During neurosurgical examination a spontaneous pathological fracture of the left femur occurred. Damage control orthopedic principals were applied and a biopsy specimen from the femoral lesion was obtained, providing a diagnosis of metastases from breast adenocarcinoma. Cesarean section was performed at 32 gestational weeks. Following delivery, an internal fixator was placed in the left femur for definitive treatment of the fracture and staging of cancer was conducted. Subsequently, adjuvant treatment comprising left mastectomy and percutaneous radiofrequency thermoablation of the sacroiliac lesion were performed. A follow-up one-year following percutaneous radiofrequency thermoablation of the sacroiliac lesion detected no metastatic bone pain, and identified a stable sacroiliac lesion.

Vaginal Intraepithelial Neoplasia: Histopathological Upgrading of Lesions and Evidence of Occult Vaginal Cancer.

OBJECTIVE: The aim of this study was to analyze women treated with excisional procedures for vaginal high-grade squamous intraepithelial lesions (HSILs). The histopathological upgrading of the lesions previously detected on vaginal biopsy and the presence of occult invasive vaginal cancer in the specimens excised were investigated, to identify a higher risk subset of women. MATERIALS AND METHODS: A retrospective analysis of the medical records of 86 women with a biopsy histopathologic diagnosis of vaginal HSIL (vaginal intraepithelial neoplasias [VaINs]: VaIN2 and VaIN3) and subsequent excisional therapy, consecutively referred to the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014, was performed. RESULTS: Of the 86 patients, 4 cases (4.6%) of occult vaginal cancer were detected, all of them in women previously diagnosed with VaIN3 on biopsy (4/39 cases, 10.3%). Women with diagnosis of VaIN2 on biopsy showed an upgrading of lesions, with diagnosis of VaIN3 on the final specimen in 5 (10.6%) of 47 cases, with no cases of VAIN2 upgraded to invasive cancer. In 33.3% of the women initially diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related disease, a final histopathological upgrading of lesions emerged. Furthermore, tobacco use was significantly related to the histopathological upgrading of lesions previously detected on vaginal biopsy. CONCLUSIONS: Women diagnosed with VaIN3 should be treated with excisional procedures as first-line surgical approach, given the risk of occult invasive disease in 10% of the cases. Women diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related cervical diseases should always be carefully evaluated and possibly excised, given the higher risk of histopathological upgrading of lesions and thus the potential risk of occult vaginal cancer. Tobacco users should be considered as high-risk group.

Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2-VaIN 3) and the cytological abnormalities on the referral pap smear.All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed.A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P = 0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P = 0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P < 0.001).The diagnosis of HG-VaIN can be preceded by different abnormalities on referral pap smear. Major abnormalities are usually reported in postmenopausal women and in women with previous cervical HPV-related disease. However, ASC-US or LSIL do not exclude HG-VaIN, especially VaIN2. An accurate examination of the whole vaginal walls (or vaginal vault) must be performed in all the women who underwent colposcopy for an abnormal pap smear, and a biopsy of all suspicious areas is mandatory.

Laser CO2 treatment for vulvar lymphedema secondary to gynecological cancer therapy: A report of two cases and review of the literature.

Vulvar lymphedema is an uncommon and disabling side-effect of pelvic lymphadenectomy and pelvic radiotherapeutic treatment for invasive genital cancer. Lymphorrhea, a complication of lymphedema, may be extremely distressing for patients due to the requirement to wear sanitary towels and as the pain and loss of elasticity of the vulvar skin and mucosa can cause discomfort during coitus. Surgical treatments of lymphorrhea and vulvar lymphedema secondary to gynecological cancer treatments remain controversial and are not currently considered to be the standard therapy. The present study reports two cases of vulvar lymphedema complicated by vulvar lymphorrhea in females who had undergone treatment for cervical and endometrial cancer, respectively; a review of the literature is also included. In the two present cases, vulvar lymphedemas were refractory to standard treatments, including decongestive therapy, manual lymph drainage, elastic bandaging, low-stretch bandaging, exercises and skin care. Laser CO2 excision and vaporization of the whole skin and mucosal tissue of the vulva was successfully performed to treat the lymphorrhea and improve quality of life. Thus, the present two cases indicated that laser CO2 surgery may present an additional therapy for the treatment of genital lymphedema that is refractory to other treatments.

Gynecologic laparoscopy in patients aged 65 or more: feasibility and safety in the presence of increased comorbidity.

OBJECTIVES: To evaluate the feasibility, operative outcome and postoperative complications of laparoscopic gynaecologic surgery in patients aged 65 or more, with increased comorbidity and obesity. STUDY DESIGN: The medical records of patients aged 65 or more with uterine or ovarian disease admitted to minimally invasive gynecologic surgery units from January 2009 to December 2011 were retrospectively analyzed in an observational cohort study. Surgical outcomes of the laparoscopic cohort (n=65) were compared with the outcomes of those who had laparotomy (n=67) at general gynecologic surgery units, and evaluated with respect to indication for surgery, medical comorbidity and obesity. Laparoscopic surgery was attempted in women who accepted minimally invasive management and who had no absolute contraindications to laparoscopy. Surgical inclusion criteria were benign and malignant uterine and adnexal pathologies; benign uterine pathologies when uterine size was less than 18 weeks' gestation or myoma smaller than 10cm; malignancies in apparent early-stage disease. There was no attempt to use laparoscopy for tumor debulking and cytoreductive surgery. Exclusion criteria were patients with emergency operations or a concomitant urogynecologic procedure. Data were analyzed using Student's t-test, the Mann-Whitney U test, χ(2) testing and the Fisher exact test. RESULTS: Patients undergoing laparoscopy had a significantly shorter hospital stay (p<0.001), less intraoperative bleeding (p<0.001), less postoperative hemoglobin decline (p<0.001), less need for blood transfusions (p=0.007) and a generally lower incidence of complications compared to women who had laparotomy, regardless of medical comorbidity. Obese patients who had laparoscopy had significantly less intraoperative bleeding and a smaller postoperative hemoglobin drop; no adjunctive complication was observed. In patients over 70 (80 cases) the laparoscopic group (39 cases) maintained significantly less intraoperative bleeding (p<0.001) and a smaller hemoglobin drop (p<0.001) with respect to laparotomy, with few postoperative complications. CONCLUSIONS: According to the results of the study, laparoscopic surgery appears feasible and safe in elderly patients, regardless of medical comorbidity and obesity.

The impact of loop electrosurgical excision procedure (LEEP) for CIN 2,3 on spontaneous preterm delivery in twin pregnancies by assisted reproductive technique: preliminary data.

The objective of this study was to compare the frequency of spontaneous preterm delivery before 35 weeks in 7 dichorionic twin pregnancies obtained after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2,3 with respect to 21 twin pregnancies without previous cervical treatment. All the pregnancies were obtained after assisted reproduction techniques (ART). Same age at delivery was observed between two groups (p = 0.81) and none of our twin pregnancies after LEEP had a threatened preterm labor while four controls (19%) underwent a spontaneous preterm delivery (p = 0.35). These preliminary data seem to indicate that LEEP may not be responsible of spontaneous preterm delivery in twin pregnancies subsequent to ART.

Knowledge of HPV infection and vaccination among vaccinated and unvaccinated teenaged girls.

OBJECTIVE: To assess the knowledge of teenaged girls on human papillomavirus (HPV) infection and vaccination 12 months after the start of a vaccine administration and information campaign. METHODS: Between May 15 and June 15, 2009, an anonymous questionnaire was given to 629 girls attending a secondary school in a northeastern Italian city (286 were vaccinated against HPV, 343 were unvaccinated) to investigate their knowledge on HPV infection, transmission, prevention, vaccination, and post-vaccination behaviors. The responses were evaluated with respect to the vaccination status of the participants. RESULTS: Vaccinated teenaged girls had no more knowledge than unvaccinated ones about the route of HPV transmission, and the relationship between HPV and AIDS. Vaccinated girls had less knowledge than unvaccinated girls about preventing transmission by condom (P=0.003) and about the correlation between HPV and penile cancer (P=0.034) and warts (P=0.001). Furthermore, compared with unvaccinated girls, more vaccinated girls believed that contraceptive pills might prevent HPV-related disease (P=0.001). Vaccinated girls better understood the importance of performing regular Pap smears after vaccination (P=0.021). CONCLUSION: Knowledge on HPV infection and vaccination remains suboptimal, especially among vaccinated teenaged girls, despite a broad information campaign. Misconceptions about the utility of secondary prevention may increase risky sexual behaviors.

Placental expression of CD100, CD72 and CD45 is dysregulated in human miscarriage.

CONTEXT AND OBJECTIVE: The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques. PATIENTS: Placenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8(th) and 12(th) week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38-40 weeks of gestation was also studied. RESULTS: CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. CONCLUSIONS: Fetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure.