Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study.

BACKGROUND: The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was to assess the long-term risk of residual/recurrent high-grade CIN. MATERIALS AND METHODS: We evaluated 760 women treated by loop electrosurgical excision procedure (684) or conization (76) between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4-14). Visits every 6 months for the first year after treatment and yearly for up to the following 10 years included cytology, colposcopy when indicated, and HPV testing (search and typing). RESULTS: CIN2+ or vaginal intraepithelial neoplasia grade 2 or worse (VAIN2+) was detected in 67 cases (8.8%), 39 at first follow-up and 28 after one/more negative visits. The risk of CIN2+ was higher in case of positive margins (odds ratio (OR) 8.04, 95% CI 4.31-15.0), type 3 transformation zone (OR for CIN3 27.7, 95% CI 2.07-36.9), CIN3+ excision (OR 6.02, 95% CI 1.73-20.9), and positive high-risk HPV test at first follow-up (OR for HPV16: 20.6, 95% CI 6.8-62.6; OR for other hrHPV types: 18.3, 95% CI 5.9-57.0). CONCLUSION: Residual/recurrent high-grade CIN occurred in <9% cases, and the risk was associated with transformation zone type, lesion grade, margins status, and hrHPV test result at 6-12 months of follow-up.

Informed cytology for triaging HPV-positive women: substudy nested in the NTCC randomized controlled trial.

BACKGROUND: Human papillomavirus (HPV)-based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status. METHODS: Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients' HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status-informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided. RESULTS: Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to 68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status-informed cytology greater than or equal to ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95% CI = 0.86 to 1.04). CONCLUSIONS: Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women.

Suicidal ideation among surgeons in Italy and Sweden - a cross-sectional study.

BACKGROUND: Suicidal ideation is more prevalent among physicians, compared to the population in general, but little is known about the factors behind surgeons' suicidal ideation. A surgeon's work environment can be competitive and characterised by degrading experiences, which could contribute to burnout, depression and even thoughts of suicide. Being a surgeon has been reported to be predictor for not seeking help when psychological distressed. The aim of the present study was to investigate to what extent surgeons in Italy and Sweden are affected by suicidal ideation, and how suicidal ideation can be associated with psychosocial work conditions. METHODS: A cross-sectional study of surgeons was performed in Italy (N = 149) and Sweden (N = 272), where having suicidal ideation was the outcome variable. Work-related factors, such as harassment, depression and social support, were also measured. RESULTS: Suicidal ideation within the previous twelve months was affirmatively reported by 18% of the Italian surgeons, and by 12% of the Swedish surgeons in the present study. The strongest association with having recent suicidal ideation for both countries was being subjected to degrading experiences/harassment at work by a senior physician. Sickness presenteeism, exhaustion and disengagement were related to recent suicidal ideation among Italian surgeons, while role conflicts and sickness presenteeism were associated with recent suicidal ideation in the Swedish group. For both countries, regular meetings to discuss situations at work were found to be protective. CONCLUSIONS: A high percentage of surgeons at two university hospitals in Italy and Sweden reported suicidal ideation during the year before the investigation. This reflects a tough workload, including sickness presenteeism, harassment at work, exhaustion/disengagement and role conflicts. Regular meetings to discuss work situations might be protective.

Confidentiality as a barrier to support seeking among physicians: the influence of psychosocial work factors in four European hospitals (the HOUPE study).

BACKGROUND: Concerns about protecting patient's privacy can interfere with proper stress adaptation which is associated with physician's health. It is important to investigate relevant organizational confounders to this phenomenon to enable interventions that can ameliorate the subjective burden of patient confidentiality. OBJECTIVES: This study investigates factors in the psychosocial work environment that can explain patient confidentiality's prominence in social support seeking among physicians, and if these factors covary differently with support seeking according to country. PARTICIPANTS: University hospital physicians in four European cities (N=2095) in Sweden, Norway, Iceland and Italy participated in a cross-sectional survey. METHODS: Questionnaire comprised items on psychosocial work environment, basic socio-demographics, presence of formal and informal meetings at work, and measurement of confidentiality as a barrier for support. RESULTS: High role conflict, availability of formal or informal meetings, lack of control over decisions, and lack of control over work pace were predictors of confidentiality as a barrier to support. There were differences between countries in how these factors covaried with confidentiality as a barrier to support. High role conflict was the strongest predictor of confidentiality as a barrier to support across all samples. CONCLUSIONS: Psychosocial work factors predicted confidentiality as a barrier to support seeking among physicians. It is important to create routines and an organizational framework that ensures both the patient's right to privacy and physician's ability to cope with emotional demanding situations from work.

Psychological and ethical implications related to infertility.

Being a parent is deeply demanding and one of the most important events in life; parents experience the deepening of human relationships with their partner, within their families, and in society, and moreover the fundamental relationship between parent and child. Every medical, social, and political effort must be made to prevent infertility but also to offer infertile couples the best diagnostic and therapeutic paths. Understanding the suffering of the couple and their families prevents and helps ease the possible psychological and social complications of infertility. Therefore, infertility concerns not only biomedical sciences but also psychological and social ones-ethics and law-in their combined efforts to identify areas of understanding and of research for solutions while respecting the dignity of the couple and unborn child. The Catholic Church offers an ongoing contribution through dialogue in looking for ethical principles guiding scientific and medical research respectful of the true life of human beings.

Work environment and recent suicidal thoughts among male university hospital physicians in Sweden and Italy: the health and organization among university hospital physicians in Europe (HOUPE) study.

BACKGROUND: Male and female physicians are at elevated suicide risk. The work environment has become a focus of attention as a possible contributor to this risk. The potential association between work environment and suicidal thoughts has been examined among female physicians in several countries, and significant findings have been reported. OBJECTIVE: The purpose of this study was to examine the role of the work environment in relation to suicidal thoughts among male university hospital physicians in 2 European countries. METHODS: Cross-sectional multivariate analysis was performed to identify significant associations between work-related factors and suicide risk among male physicians from the Health and Organization among University Hospital Physicians in Europe (HOUPE) study. The dependent variable was termed recent suicidal thoughts, which includes having thought about suicide and/or having thought about specific ways to commit suicide within the previous year. Adjusted odds ratios (ORs) and CIs are reported. RESULTS: Of the 456 Swedish (56%) and 241 Italian (39%) male physicians who participated, 12% of the physicians from each country reported affirmatively regarding recent suicidal thoughts. Degrading work experiences were associated with recent suicidal thoughts for the Swedish and Italian physicians (OR = 2.1; 95% CI, 1.01-4.5; OR = 3.3; 95% CI, 1.3-8.0, respectively). Role conflict was associated with recent suicidal thoughts among the Swedish physicians (OR = 1.6; 95% CI, 1.1-2.2). Support at work when difficulties arose appeared to be protective for the Swedish physicians (OR = 0.7; 95% CI, 0.5-0.96). Italian physicians with little control over working conditions had an increased risk of recent suicidal thoughts, whereas confidential discussions about work experiences appeared to be protective (OR = 0.6; 95% CI, 0.4-0.9). CONCLUSION: Attention should be paid to the work environment as it relates to suicide risk among male university hospital physicians, particularly to bolstering social support and preventing harassment.

Triage of women with atypical squamous cells of undetermined significance (ASC-US): results of an Italian multicentric study.

OBJECTIVES: To compare the performance of immediate colposcopy, repeat Pap test and HPV test as triage options for women diagnosed as having atypical squamous cells of undetermined significance (ASC-US) while attending organised screening for cervical carcinoma in five centres of the Veneto region. METHODS: Women consecutively diagnosed as having ASC-US were included in a prospective study, and underwent colposcopy and collection of cervico-vaginal cells for conventional Pap test and HPV test (Hybrid Capture 2, High-risk probe set, Digene). Repetition of all three tests was scheduled for 12 months later. DNA was subsequently extracted from residual cells of positive samples, and analysed by polymerase chain reaction with several primers for typing of HPV sequences. Sensitivity, specificity and positive predictive value (PPV) of the different triage options for histology-confirmed cervical intraepithelial neoplasia, grade 2 or worse (CIN2+) were calculated among all women and by age (under and above 35 years). RESULTS: Seven hundred forty-nine women 25-64 years old (median age 42 years) were enrolled in the study. Pap smears at enrolment were read as ASC-US or more severe in 211 (29.4%) cases, colposcopy disclosed an atypical transformation zone in 254 (34.2%) women, and HPV test was positive in 181 (24.2%). High-grade cervical lesions developed in 29/749 (3.9%) women. HPV typing was possible in 163 (90%) of the samples, and carcinogenic types were present in 123. CONCLUSIONS: HPV test showed the best performance; overall, it had the highest sensitivity (92.3%), specificity (78.6%) and PPV (14.9%).

Survey on recent suicidal ideation among female university hospital physicians in Sweden and Italy (the HOUPE study): cross-sectional associations with work stressors.

BACKGROUND: Suicide rates among physicians are higher than in the general population, and rates among female physicians are particularly high. More female than male physicians report suicidal thoughts, with suicidal ideation being a well-recognized precursor of suicide. The urgent need to find the reasons for suicide risk in female physicians is underscored by society's increasing dependence on this group of health care providers. OBJECTIVE: The aim of this paper was to identify potential risk and protective factors associated with recent suicidal ideation in female physicians. METHODS: A cross-sectional survey analysis of work-related health, organizational culture, career paths, and working conditions was performed among permanently employed female physicians from the HOUPE (Health and Organisation among University Physicians in four European countries) study: 385 in Sweden and 126 in Italy. The main outcome measure was recent (within the prior 12 months) suicidal thoughts. RESULTS: Overall, 13.7% and 14.3% of the participants from Sweden and Italy, respectively, reported suicidal thoughts within the prior 12 months. Among the physicians from Sweden, the most powerful multivariate model for such thoughts included 2 independent variables related to work: degrading experiences/harassment at work (odds ratio [OR], 3.03; 95% CI, 1.48-6.23), and work meetings to discuss stressful situations (OR, 0.36; 95% CI, 0.19-0.69). The model included self-diagnosis and self-treatment as a significant factor. Work meetings to discuss stressful situations were also in the multivariate model for the Italian physicians (OR, 0.21; 95% CI, 0.05-0.86), together with being given work assignments without adequate resources (OR, 5.0; 95% CI, 1.32-18.8). Significant non-work-related factors in the Italian model were younger age and seeking professional help for depression or burnout. CONCLUSIONS: In both Sweden and Italy, work stressors have been identified that may increase the risk for suicide for female physicians. A potential protective factor was meetings to discuss stressful work experiences. These findings suggest that such meetings should be more broadly implemented.

Successful topical treatment with mitomycin-C in a female with post-brachytherapy vaginal stricture.

Vaginal strictures are rare entities in pediatric population, mainly due to congenital genito-urinary tract malformations and sequelae of their surgical treatment, recurrent vaginitis and multisciplinary therapy for malignant tumors. The therapy of choice is not standardized. Conservative treatments are favored and dilators seem to be very effective, but their use in children is difficult due to poor compliance. We report our experience with topical application of mitomycin-C in a female with vaginal stricture secondary to brachytherapy.

Results at recruitment from a randomized controlled trial comparing human papillomavirus testing alone with conventional cytology as the primary cervical cancer screening test.

BACKGROUND: In the first recruitment phase of a randomized trial of cervical cancer screening methods (New Technologies for Cervical Cancer Screening [NTCC] study), we compared screening with conventional cytology with screening by human papillomavirus (HPV) testing in combination with liquid-based cytology. HPV-positive women were directly referred to colposcopy if aged 35 or older; if younger, they were retested after 1 year. METHODS: In the second recruitment phase of NTCC, we randomly assigned women to conventional cytology (n = 24,661) with referral to colposcopy if cytology indicated atypical squamous cells of undetermined significance or more severe abnormality or to testing for high-risk HPV DNA alone by Hybrid Capture 2 (n = 24,535) with referral to colposcopy if the test was positive at a concentration of HPV DNA 1 pg/mL or greater. For the main endpoint of the study, histologic detection of cervical intraepithelial neoplasia of grade 2 or more (CIN2+), we calculated and compared sensitivity and positive predictive value (PPV) of the two screening methods using HPV DNA cutoffs of 1 pg/mL and 2 pg/mL. All statistical tests were two-sided. RESULTS: For women aged 35-60 years, the relative sensitivity of HPV testing for detection of CIN2+ at a cutoff of 1 pg/mL vs conventional cytology was 1.92 (95% CI = 1.28 to 2.87) and the relative PPV was 0.80 (95% CI = 0.55 to 1.18). At a cutoff of 2 pg/mL HPV DNA, the relative sensitivity was 1.81 (95% CI = 1.20 to 2.72) and the relative PPV was 0.99 (95% CI = 0.67 to 1.46). In this age group, there was no evidence of heterogeneity between study phases. Among women aged 25-34 years, the relative sensitivity for detection of CIN2+ of HPV testing at a cutoff of 1 pg/mL vs cytology was 3.50 (95% CI = 2.11 to 5.82), statistically significantly larger (P = .019) than that observed in phase 1 at this age (1.58; 95% CI = 1.03 to 2.44). CONCLUSIONS: For women aged 35-60 years, HPV testing with a cutoff of 2 pg/mL achieves a substantial gain in sensitivity over cytology with only a small reduction in PPV. Among women aged 25-34 years, the large relative sensitivity of HPV testing compared with conventional cytology and the difference between relative sensitivity during phases 1 and 2 suggests that there is frequent regression of CIN2+ that are detected by direct referral of younger HPV-positive women to colposcopy. Thus, triage test or repeat testing is needed if HPV is to be used for primary testing in this context.

The New Technologies for Cervical Cancer Screening randomised controlled trial. An overview of results during the first phase of recruitment.

OBJECTIVES: To study the impact of different cervical cancer screening strategies including HPV testing. METHODS: A randomised controlled trial with a conventional arm (conventional cytology) and an experimental arm following two phases (first HPV testing+conventional cytology, second HPV testing alone). In phase one, different protocols were applied to different age groups (25-34 and 35-60). Published data on test accuracy during the phase one of recruitment are summarised. RESULTS: 45,307 women were recruited in phase one (about 95,000 overall). In the age group 35-60, HPV testing (by Hybrid Capture 2) alone at 2 RLU cut-off increased sensitivity vs. conventional cytology (relative sensitivity 1.41; 95% CI: 0.98-1.02) with a small loss in Positive Predictive Value (PPV; relative PPV 0.75; 95% CI: 0.45-1.25). Adding liquid-based cytology as screening test and referring to colposcopy women positive to either only marginally increased sensitivity but strongly reduced PPV. In the age group 25-34, similar results (relative sensitivity vs. conventional cytology 1.58; 95% CI: 1.032.44; relative PPV 0.78; 95% CI: 0.72-1.16) were obtained, despite 14% of women were HPV positive, with a strategy based on HPV alone as screening test, triaging HPV positive women by cytology, directly referring those ASCUS+ to colposcopy and repeating both tests after 1 year in those with normal cytology. CONCLUSIONS: HPV testing, if used as screening test, should be applied alone, with cytology triage essential in younger women but preferable at all ages. Follow-up data will allow analysis of the safety of prolonging screening intervals and the relative persistence of lesions detected with different methods.

Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening: randomised controlled trial.

OBJECTIVE: To compare the accuracy of conventional cytology with liquid based cytology for primary screening of cervical cancer. DESIGN: Randomised controlled trial. SETTING: Nine screening programmes in Italy. PARTICIPANTS: Women aged 25-60 attending for a new screening round: 22 466 were assigned to the conventional arm and 22 708 were assigned to the experimental arm. INTERVENTIONS: Conventional cytology compared with liquid based cytology and testing for human papillomavirus. MAIN OUTCOME MEASURE: Relative sensitivity for cervical intraepithelial neoplasia of grade 2 or more at blindly reviewed histology, with atypical cells of undetermined significance or more severe cytology considered a positive result. RESULTS: In an intention to screen analysis liquid based cytology showed no significant increase in sensitivity for cervical intraepithelial neoplasia of grade 2 or more (relative sensitivity 1.17, 95% confidence interval 0.87 to 1.56) whereas the positive predictive value was reduced (relative positive predictive value v conventional cytology 0.58, 0.44 to 0.77). Liquid based cytology detected more lesions of grade 1 or more (relative sensitivity 1.68, 1.40 to 2.02), with a larger increase among women aged 25-34 (P for heterogeneity 0.0006), but did not detect more lesions of grade 3 or more (relative sensitivity 0.84, 0.56 to 1.25). Results were similar when only low grade intraepithelial lesions or more severe cytology were considered a positive result. No evidence was found of heterogeneity between centres or of improvement with increasing time from start of the study. The relative frequency of women with at least one unsatisfactory result was lower with liquid based cytology (0.62, 0.56 to 0.69). CONCLUSION: Liquid based cytology showed no statistically significant difference in sensitivity to conventional cytology for detection of cervical intraepithelial neoplasia of grade 2 or more. More positive results were found, however, leading to a lower positive predictive value. A large reduction in unsatisfactory smears was evident. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81678807 [controlled-trials.com].

Plasma exchange in the management of high risk pregnant patients with primary antiphospholipid syndrome. A report of 9 cases and a review of the literature.

A second-line treatment protocol including plasma exchange (PE) in addition to the standard therapies was scheduled and utilized in our hospital with the intent of improving the outcome of high risk pregnancies of women with primary antiphospholipid syndrome (APS). This paper chronologically reports and discusses the results obtained in these patients over a 15-year period. Between April 1991 and September 2006, 142 pregnancies of patients with APS were followed by us. Nine of these (6.3%), who did not respond to the conventional procedures or showed complications during the treatments were shifted to a PE protocol management. All these women had a history of previous thromboembolism associated to triple antiphospholipid antibody positivity. Nine pregnancies of 7 patients (2 women were treated twice) were thus followed using PE therapy, which has undergone modification over the years. In the cases studied the outcome of pregnancy varied according to the different PE therapy conditions. This study suggests that prophylactic PE treatment administered along with full anticoagulation and IVIG therapy could be a valuable therapeutic option in high risk pregnant APS women. Further studies in this type of patients are certainly warranted.

Human papillomavirus typing of invasive cervical cancers in Italy.

BACKGROUND: Human papilloma viruses (HPV) are the necessary cause of invasive cervical cancer (ICC). Of the many different types identified so far, only a few of them account for the great majority of cases worldwide, with geographical differences in their distribution. Data on the local distribution are now of interest in view of the soon-to-come introduction of HPV type-specific prophylactic vaccines. RESULTS: We have investigated HPV type distribution in samples of 48 ICC cases occurred in women living in North-East Italy in the years 1997-1999. Cases were extracted from the Venetian Tumour Registry files, as incident cases whose specimens had been processed in two Pathology Departments. Search and typing were performed by polymerase chain reaction (PCR) using GP5+/GP6+ primers, followed by direct sequencing or reverse dot blot. Three cases were PCR negative using the housekeeping primers and hence excluded. One case was negative by all HPV tests used. HPV 16 was present in 32 (72.7%) cases, as single infection in 28, in mixed infection in 4. Of the 44 positive cases, HPV 16 and HPV 18 accounted for 33 (75%), as single or mixed infections. The other high risk HPV types accounted for 11 (25%) of the remaining infections. Of the 32 HPV 16 positive cases, sequencing of the E6 gene could be performed in 25; the prototype isolate was identified in 7, and the variant T350G in 18; in 4 cases one or more additional mutations were present. CONCLUSIONS: Our results suggest that HPV 16 has a very high prevalence among women with invasive cervical cancer in Italy; therefore, the use of a prophylactic vaccine for HPV types 16 and 18 could prevent up to 75% of invasive cervical cancers in Italy.

Ballantyne syndrome: a case report.

Ballantyne syndrome (also called mirror syndrome or triple edema) describes the unusual association of fetal and placental hydrops with maternal preeclampsia. This is a case report illustrating a 37-year-old patient who was referred to our clinics at 28 weeks of gestation (wg) because of fetal hydrothorax. On examination, the woman did not show signs of preeclampsia. The fetal ultrasound examination revealed bulky hydrothorax, generalized subcutaneous edema, placental edema, and polyhydramnios. It was not possible to find the cause of the fetal hydrops. At 29 weeks and 4 days of gestation, the fetal hydrothorax was removed by two pleuro-amniotic shunts, but at the moment of our intervention anasarca was already present. In the following 3 days, despite observing bed rest, the mother developed edema of hands and face, while blood pressure remained normal. At 30 wg the patient underwent cesarean section because fetal movements ceased and the fetal heart rate monitoring showed loss of variability and decelerations. Before dying, the neonate lived for 20 days in a state of deep hypotension.

Antiretroviral therapy and the clinical evolution of human papillomavirus-associated genital lesions in HIV-positive women.

The effect of antiretroviral therapy on the natural history of human papillomavirus (HPV)-associated genital lesions was evaluated in 201 human immunodeficiency virus (HIV)-infected women who were followed-up for 1-6 years. Gynecologic examinations were performed every 6-12 months. HPV sequences in cervico-vaginal cells, analyzed by polymerase chain reaction and typed by restriction fragment-length polymorphism analysis, were repeatedly detected in 126 women; 29 had transient HPV infection. Genital lesions were found in 137 patients; prevalence was comparable in women who were receiving different antiretroviral regimens. Regression of low-grade lesions was more prevalent among patients receiving highly active antiretroviral therapy than among those receiving other regimens; high-grade lesions regressed in the majority of cases, regardless of antiretroviral therapy. HPV infection persisted in nearly 80% of the cases. In conclusion, our data show that antiretroviral therapy does not prevent the development of HPV-associated lesions and does not eliminate HPV infection; therefore, early and strict gynecologic follow-up of HIV-infected women is warranted.