Molecular analysis of endometrial inflammation in preterm birth.

Spontaneous preterm birth (sPTB) represents the 35%-45% of all preterm birth (PTB) cases and its etiology is unknown. We investigated if the expression level of endometrial cytokines and angiogenetic factors is related to the onset of sPTB.Endometrial tissues from non-pregnant women who experienced sPTB and from non-pregnant women who did not experience sPTB were collected and examined for their expression profile. With this aim, the PCR Array analysis was performed and data were confirmed by Real-Time PCR. Differential gene expression measurements (pathological vs control tissues) showed a significant up-regulation for genes codifying for two angiogenetic factors known as connective tissue growth factor (CTGF), and coagulation factor III (F3). An increased level of expression was detected both for tyrosine kinase endothelial (TEK) and for transforming growth factor beta 2 (TGF-ß2) genes but without reaching the statistical significance. The expression level of interleukin 10 receptor alpha (IL10RA) gene was slightly decreased in pathological group compared to control one but, as well as forTEK and TGF-ß2 measurements, without reaching the statistical significance. Our work is the first to correlate the imbalance in endometrial district of non -pregnant women with sPTB. These data could suggest a new point of view whence to read sPTB. We need additional clinical and biological studies to clarify sPTB pathogenesis.

Predictors of malignancy in endometrial polyps: a multi-institutional cohort study.

PURPOSE OF INVESTIGATION: The risk of endometrial cancer in women with endometrial polyps (EPs) has been reported to vary between 0.3% and 4.8%. There is a lack of data about the management of asymptomatic women with incidental diagnosis of EPs. In the present study the authors correlated demographic and clinical characteristics with histopathological features of the EPs hysteroscopically removed. MATERIALS AND METHODS: An observational multi-institutional cohort study was conducted from February 2010 to December 2012 to identify all the premenopausal and postmenopausal women consecutively undergoing hysteroscopic polypectomy. The data of women were reviewed and clinical features were related to histopathologic results. RESULTS: The patients recruited were 813. The mean age was 52.5 years (range 22-87). The results showed a correlation between older age, high body mass index (BMI) and obesity, postmenopausal state, abnormal uterine bleeding (AUB), hypertension, and risk of malignant EPs. On multivariable analysis, the correlation remained only for age (OR 1.08, 95% CI 1.03 - 1.14) and AUB (OR 3.53, 95% CI 1.87 - 6.65). CONCLUSION: Older patients in postmenopausal status with AUB, a high BMI, and hypertension are at higher risk for premalignant and malignant polyps. In these patients a surgical approach should be used, consisting in hysteroscopical removing of the polyp.

Risk of recurrent menorrhagia after hydrothermoablation: role of GnRH analogues neoadjuvant treatment in long-term successful rate.

OBJECTIVE: To evaluate the long-term effectiveness of presurgical therapy with GnRH analogues in patients who underwenthydrothermal endometrial ablation (HTA) for menorrhagia and assess the relationship between sonographically measured myometrium thickness and pelvic pain. MATERIALS AND METHODS: A prospective randomized control study comparing 15 women (Group A) with presurgical subcutaneous triptorelin depot injection before HTA with controls (Group B, n = 15). Inclusion criteria were: recurrent menorrhagia, uterus length < 12 cm, no previous hormonal therapy for at least six month, and family plan completed. Student's t test was applied, as appropriate, to compare continuous variables. Proportion were compared with chi-squared. RESULTS: After 12 months of follow-up, Group A showed a significantly lower (0% vs 20%; p = 0.03) failure rate after hydrothermoablation than the Group B and a generally higher successful rate at 24 and 48 months. The discomfort, evaluated with VAS, showed a mean value of 47.6 +/- 15.9 +/- SD); 96.7% of women reported a mild-moderate postoperative pain. No perioperative and late complications were recorded. CONCLUSIONS: Presurgical treatment with GnRH analogues seems to improve long-term efficacy of HTA. Perioperative pelvic pain seems to not be affected by myometrium thickness.

Cervical pessary for preterm birth prevention after an episode of arrested preterm labor: a retrospective cohort study with targeted maximum likelihood estimation of the average treatment effect.

OBJECTIVE: To evaluate whether cervical pessary effectively reduces the preterm birth < 37 weeks rate in patients who have not delivered after an episode of arrested preterm labor. PATIENTS AND METHODS: Retrospective cohort study was conducted on singleton pregnant patients admitted to our institution between January 2016 and June 2021 for threatened preterm labor and who had a cervical length < 25 mm. Women in whom a cervical pessary was placed were considered as exposed, while women in whom expectant management was preferred were considered as unexposed. The primary outcome was the rate of preterm birth before 37 weeks. A targeted maximum likelihood estimation was used to estimate the average treatment effect of cervical pessary by adjusting for a-priori-defined confounders. RESULTS: A cervical pessary was placed in 152 (36.6%) patients (exposed), while the remaining 263 (63.4%) were managed expectantly (unexposed). The adjusted average treatment effect was -14% (-18 to -11%), -17% (-20 to -13%), and -16% (-20 to -12%) for preterm birth < 37 weeks, < 34 weeks, and < 32 weeks, respectively. The average treatment effect for adverse neonatal outcomes was -7% (-8 to -5%). No difference in gestational weeks at delivery between exposed and unexposed emerged when gestational age at first admission was > 30.1 gestational weeks. CONCLUSIONS: The positioning of a cervical pessary placement may be evaluated to reduce the risk of a subsequent preterm birth after an episode of arrested preterm labor in pregnant patients with onset of symptoms before 30 gestational weeks.

Teenagers' knowledge about HPV infection and HPV vaccination in the first year of the public vaccination programme.

The aim of this study was to assess teens' knowledge of HPV infection and vaccination one year after the initiation of the public vaccination programme and information campaign on the disease and the opportunity of vaccination. Between 15 May and 15 June 2009, a survey was carried out on 1,105 teenagers attending high schools in a town in the northeast of Italy by means of an anonymous and unannounced questionnaire covering the knowledge of HPV infection, transmission, prevention, vaccination and post-vaccination behaviours. Only 75% of teens knew what HPV infection is (92% of girls vs 51% of boys, p < 0.001); only 70% knew that it is a sexually-transmitted infection. Only 69.3% associated condoms with HPV disease prevention (72.6% girls vs 61.5% boys, p = 0.002). About 18.8% of girls and 33.2% of boys believe that HPV can lead to AIDS (p < 0.001). Among teens aware of HPV vaccination, 7.6% of girls and 21.8% of boys believe that it can prevent AIDS (p < 0.001). Only 75.5% of girls and 51.1% of boys (p < 0.001) believe that condom use remains useful for HPV prevention after vaccination. The need for regular pap smears after vaccination is reported by 93.3% of girls. Teens' knowledge about HPV infection and vaccination remains insufficient, despite a broad information campaign. Erroneous information may increase risky sexual behaviours. Without complete information about HPV infection and vaccination and information about other sexually-transmitted diseases, the latter might become difficult to control among teenagers, while some misunderstandings about the usefulness of secondary prevention might linger.

European consensus statement on essential colposcopy.

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix.

Atrophic endometrium in postmenopausal women referred to diagnostic hysteroscopy: a study to avoid unnecessary examinations.

OBJECTIVE: Any diagnostic workup should be based on appropriateness criteria. Diagnostic hysteroscopy is a procedure widely used in endometrial pathology. Its high outpatient feasibility frequently leads to misuse. However, it can cause discomfort and, albeit rarely, complications. The present study aimed to provide an estimate of unnecessary examinations based on variables associated with atrophic endometrium in postmenopausal women referred to diagnostic hysteroscopy. PATIENTS AND METHODS: One-hundred and sixty-six postmenopausal women undergoing hysteroscopy were retrospectively analyzed. All included women had a final histological reference standard. The sample was divided into women with atrophic endometrium vs. women with endocavitary lesions (benign/premalignant/malignant). Univariate and multivariate analysis was performed to assess those patient characteristics associated with atrophic endometrium. Furthermore, based on the likelihood ratios, a post-test probability analysis was performed to provide an estimate of atrophy according to the presence of specific variables. RESULTS: Sixty-one postmenopausal women (36.7%) undergoing diagnostic hysteroscopy showed atrophic endometrium at final histology. Multivariate analysis showed that the independent variables associated with atrophy were the absence of abnormal uterine bleeding [Odds Ratio (OR)=6.43, Confidence Intervals (CI) 2.087 to 19.822], and endometrial thickness (criterion < 7 mm) (OR=0.417, CI 0.300 to 0.578). In women showing both variables associated with negative endometrial outcome, post-test probability analysis resulted in an atrophic endometrium rate of 89.13%, from a pre-test probability of 36.7%. CONCLUSIONS: About 90% of asymptomatic postmenopausal women with endometrial thickness <7 mm resulted in an atrophic endometrium at hysteroscopy. Every gynecologist should know and consider these data before referring such women to further examinations. In these cases, diagnostic hysteroscopy is not cost-effective leading to a high number of false positives.

Sensitivity and specificity values of high-risk HPV DNA, p16/ki-67 and HPV mRNA in young women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL).

OBJECTIVE: The aim of the study was to evaluate the sensitivity and specificity values of high-risk HPV DNA test, p16/ki-67, and HPV mRNA in histologically high-grade cervical intraepithelial lesions (CIN2-CIN3) in women aged 21-24 years with diagnosis of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) at pap smear. PATIENTS AND METHODS: 342 patients between 21-24 years old, attending spontaneously our clinics, 118 with ASCUS and 224 with LSIL, were enrolled in the study. All patients underwent colposcopy and biopsies were performed in the areas with major changes. All patients were tested at the same time for p16/ki-67, high-risk HPV DNA and HPV mRNA. RESULTS: Nineteen out of 118 women with ASCUS showed a high-grade cervical intraepithelial lesion, 11 out of 118 (9.32%) CIN2, and 8 out of 118 (6.78%) CIN3. The sensitivity of high-risk HPV DNA was 99.9%, and the specificity 23.2%; p16/ki-67 pointed out a sensitivity of 90.9%, and a specificity of 81.8%; HPV mRNA showed a sensitivity of 81.8%, and specificity of 87.9% in CIN2 lesions. In CIN3 lesions, the sensitivity of high-risk HPV DNA was 99.9%, while the specificity was 19.1%; p16/ki-67 showed a sensitivity of 99.9%, and a specificity of 73.7%; HPV mRNA relived a sensitivity of 87.5%, and a specificity of 80.8%. In women with LSIL, a total of 42/224 (18.75%) of CIN2 were found at the histopathological examination, while 17/224 (7.59%) women presented a CIN3. No case of invasive cancer was identified. High-risk HPV DNA was positive in 190/224 (84.8%), p16/ki-67 in 119/224 (53.1%), and HPV mRNA in 104/224 (46.4%). In women with CIN2, the sensitivity of high-risk HPV DNA was of 92.8%, and the specificity 17.5%, the sensitivity of p16/ki-67 was 95.2%, and specificity 61.8%. HPV mRNA showed a sensitivity of 88.8% and a specificity of 87.8%. In women with CIN3, the sensitivity of high-risk HPV DNA was 88.2%, and the specificity 29.7%; p16/ki-67 pointed out a sensitivity of 94.1%, and a specificity of 49%; HPV mRNA showed a sensitivity of 88.2% and a specificity of 80.6. CONCLUSIONS: Taking into account the high rate of spontaneous regression of high-grade lesions in young women, these tests, in particular, the HPV mRNA test, used as a triage test for ASCUS or LSIL, can modify follow-up triage strategy. In fact, this biomarker, due to its high specificity, could lead to a cytology repetition instead of an immediate colposcopy, avoiding over diagnosis and potential overtreatment in this category of women.

Vaginal natural oxygenation device (VNOD) for concomitant administration of hyaluronic acid and topical hyperbaric oxygen to treat vulvo-vaginal atrophy: a pilot study.

OBJECTIVE: This is a pilot study to evaluate the effectiveness of concomitant administration of hyaluronic acid and topical hyperbaric oxygen therapy (THOT) by a specifically designed medical device (vaginal natural oxygenation device, VNOD) in improving the symptomatology of postmenopausal patients with vulvo-vaginal atrophy (VVA). PATIENTS AND METHODS: Women with diagnosis of severe VVA from September 2017 to May 2018 were included. Five biweekly administration of THOT and concomitant of hyaluronic acid were performed with a specifically designed medical device. In each occasion, the intensity of patient's symptoms (well-being such as absence of dyspareunia, vaginal dryness, vulvar and/or vaginal itching; vaginal burning; presence of fluid) was determined with a graduated scale from 1 to 6 and the vaginal elasticity and the vaginal wall epithelium appearance were also determined with a graduated scale from 1 to 5. The change in all parameters from baseline to end of therapy was evaluated. RESULTS: Twenty-five patients were considered for the final analysis. A significant improvement in well-being (0.3 vs. 5.1, p < 0.001), vaginal burning (0.2 vs. 5.1, p < 0.001), presence of fluid (0.6 vs. 4.9, p < 0.001), vaginal epithelium appearance (1.8 vs. 4.7, p < 0.001), and vaginal elasticity (1.1 vs. 3.8, p < 0.001) was observed between the first and the last therapy session. All the patients reported a recovery of their sexuality at the end of the five treatment sessions. CONCLUSIONS: In this pilot study, the use of VNOD seems to be a valid treatment of VVA, resulting in a completely natural type of therapy well accepted by patients with immediate therapeutic effects and without side effects; these findings must be confirmed in a well-designed randomized controlled trial.

Preterm birth after loop electrosurgical excision procedure (LEEP): how cone features and microbiota could influence the pregnancy outcome.

OBJECTIVE: In the last years, the mean age of women who underwent cervical treatment for high-grade cervical intraepithelial neoplasia (CIN 2-3) is similar to the age of women having their first pregnancy. The aim of this study was to evaluate the risk of preterm birth in subsequent pregnancies after loop electrosurgical excision procedure (LEEP). PATIENTS AND METHODS: From January 2013 to January 2016 the study identified a total of 1435 women, nulliparous, who underwent LEEP for CIN 2-3, and who wished to have their first pregnancy. Before surgery, the lengths of the cervix were calculated by transvaginal sonography. After the treatment, the dimension of the removed tissue was evaluated. During the pregnancy, all women carried out periodic transvaginal sonography and vaginal-cervical swabs. RESULTS: The average age of patients was 31.96±5.24 years; the interval between the surgical procedure and pregnancy was 12.04±4.67 months; the gestational age at births was 37.53±2.91 weeks. The first vaginal and cervical swab performed during pregnancy was negative in 81.8% of patients. The most prevalent infections were related to C. Albicans, G. Vaginalis, and Group B Streptococcus (GBS). The rate of preterm delivery was significantly higher in women with a minor cervical length. CONCLUSIONS: The length and the volume of cervical tissue excised have been shown to be directly related to the risk for preterm birth. Furthermore, vaginal infections and their persistence during pregnancy in women with a history of LEEP may be associated with an increased risk for preterm birth, compared with women with no history of LEEP.

Relationship between maternal hemodynamics and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia and fetal growth restriction.

OBJECTIVE: A proper maternal cardiovascular adaptation to the pregnancy plays a key role for promoting an adequate uteroplacental perfusion, for ensuring normal fetal development and for preventing gestational hypertensive complications such as preeclampsia. This study aims to evaluate hemodynamic measurements obtained by noninvasive methods among preclamptic women with and without fetal growth restriction (FGR) and the relationship with plasma levels of natriuretic peptides. STUDY DESIGN: The study compared 98 pregnant women (n=48 with preeclampsia; n=50 normotensive pregnant women) and 50 nonpregnant normotensive control subjects undergoing anultrasonic cardiac output monitor (USCOM) and plasma assessment of atrial N-terminal pro B-type natriuretic peptide (NT-proBNP). The statistical analysis was carried out by analysis of variance and correlation analysis. RESULTS: Preeclampsia state is associated with increased vascular resistance (mean 1587±236 vs 978±153 dyn s cm-3) and lower cardiac output (mean 5.7±1.1 vs 6.78±0.8 l) and this hemodynamic state is associated with higher levels of NT-proBNP (mean 121.2±26.3 vs 42.5±11.4 pg ml-1); furthermore, we found an inverse correlation between maternal cardiac output and plasma levels of NT-proBNP only if preeclampsia is associated with FGR. CONCLUSION: The elevated NT-proBNP in preeclampsia may reflect ventricular stress and subclinical cardiac dysfunction worsening if FGR is present. This may have implications for the acute management of the preeclampsia and FGR women and for appropriately timed therapeutic interventions later in life.

Detection of occult endocervical glandular dysplasia in cervical conization specimens for squamous lesions.

The aim of this work was to evaluate the incidence of occult cervical glandular intraepithelial neoplasia (CGIN) and adenocarcinoma of the cervix (AC) in women treated with CO2-laser conization for cervical intraepithelial neoplasia (CIN) or squamocellular cervical cancer (SCC). The medical records of all women with a histological diagnosis of squamous lesions of the uterine cervix (persistent CIN1, CIN2, CIN3 and SCC) who were subsequently treated with CO2-laser conization at our institution, during the period from January 1991 to December 2014, were analyzed in a retrospective case series. Among the 1004 women fulfilling the study inclusion/exclusion criteria, 77 cases (7.7%) of occult glandular lesions (CGIN and AC) were detected on the final cone specimen (48 cases of occult low-grade cervical glandular intraepithelial neoplasia (LCGIN), 25 cases of occult high-grade cervical glandular intraepithelial neoplasia (HCGIN), and four cases of occult "usual-type" AC). No difference in the mean age between women diagnosed with occult glandular lesions and women without occult glandular lesions on the final specimen emerged (39.1±9.3 vs 38.4±9.4, p=0.5). In women with occult LCGIN on cone specimen, mean follow-up of 48 months was reported (range 7-206 months) and no cases of progression to HCGIN or AC were observed. In conclusion, a relatively high rate of occult glandular lesions was found in women treated for squamous lesions. The natural history of CGIN is still uncertain and, in particular, there are some controversies as to whether LCGIN is a precursor lesion of HCGIN or AC. In this context the role of pathologists become very important since the appropriate diagnosis of these lesions could have potential implications in the clinical management of these patients.

Trend of decreasing length of cervical cone excision during the last 20 years.

OBJECTIVE: The aim of the present investigation was to evaluate the cervical conizations performed in the last 20 years in a single institution, with a particular interest in analyzing the trend of the length of cone excisions. PATIENTS AND METHODS: A retrospective cohort study of women who underwent a CO2-laser cervical conization between January 1996 and December 2015. Cytological abnormalities on referral pap smear, colposcopic findings and pertinent clinical and socio-demographic characteristics of each woman were collected. In particular, the length of cone specimen was evaluated, taking into account all the factors potentially influencing the length of excision. RESULTS: A total of 1270 women who underwent cervical conization from January 1996 to December 2015 were included in the analysis. A mean cone length of 15.1 ± 5.7 mm was reported, and we observed a significant decrease in the length of cone excisions over the whole study period. Age (rpartial = 0.1543, p < 0.0001), see & treat procedure (rpartial = -0.1945, p < 0.0001) and grade II colposcopic findings (rpartial = 0.1540, p < 0.0001) were significantly associated with the length of cone excision on multivariate analysis. CONCLUSIONS: In the last 20 years, a significant decrease in the length of cone excision was observed. In our opinion, this can be due to the acquired awareness by the gynecologists of the potential disadvantages of wide cone excision in term of adverse obstetric outcomes in future pregnancies.

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.

Laparoscopic colorectal resection for endometriosis.

BACKGROUND: The rectosigmoid colon is affected by deep pelvic endometriosis in 3-37% of cases. In the past, treatment of the affected gastrointestinal tract generally required conversion to conventional surgery. We describe our experience with complete laparoscopic management of deep pelvic endometriosis with bowel involvement. METHODS: From March 1995 to March 2003, 29 consecutive patients with endometriosis requiring laparoscopic intervention were evaluated. In seven patients (24%) colorectal involvement was identified prior to the operation. A low anterior resection was performed in four patients (57%) and a sigmoid resection in three (43%). In all cases, colonoscopy showed a normal mucosa. In all cases, treatment consisted of resection of the bowel involved together with the excision of all other implants. Data analysis included age, previous abdominal operations, previous history of endometriosis, operative time, conversion rate, complications, length of stay, and pain relief. RESULTS: There were seven patients with colorectal involvement whose median age was 32.8 years (range, 28-40), with a history of previous abdominal operation in two (28%). Preoperative symptoms were as follow: dysmenorrea in four patients (57%), dyspareunia in four (57%), pelvic pain in seven (100%), rectal bleeding in one (14%), and tenesmus in five (71%). Mean operative time was 190 min (range, 165-230). Length of stay was 8.3 days (range, 7-11). There were no anastomotic leak and no major postoperative complication. One patient had temporary urinary retention. At a median follow-up of 38.7 months (range, 1-84), complete relief of pelvic symptoms was achieved in five patients (71%), and there was improvement in one patient. In one patient complaining of persistent pain, a new colonic implant was diagnosed two years after the surgery requiring reoperation. CONCLUSIONS: The results show that provided that the surgeon is highly skilled in laparoscopy, laparoscopic resection of deep pelvic endometriosis with rectosigmoid involvement is feasible and effective in nearly all patients.

High temperature requirement A1, transforming growth factor beta1, phosphoSmad2 and Ki67 in eutopic and ectopic endometrium of women with endometriosis.

Increasing evidence supports the hypothesis that TGFb1 signalling may be mediated by high temperature requirement A1 (HtrA1) serine protease, acting on important regulatory mechanisms such as cell proliferation and mobility. Evidence is now accumulating to suggest that HtrA1 is involved in the development and progression of several pathologies. The aim of this study was to evaluate: i) if HtrA1 and TGFb1 expressions differ in eutopic and ectopic endometrium in women with endometriosis; ii) if HtrA1 correlates to TGFb1, pSmad and Ki67. This study was carried out including 10 women with ovarian endometriosis (cases) and 10 women with non endometriotic diseases (controls). Endometrial tissue underwent immunohistochemical H-score analysis for HtrA1, TGFb1, pSmad and Ki67 molecules. Data evaluation was performed by a nonparametric Kruskal-Wallis test and Spearman correlation was applied to evaluate the relationship among the molecules investigated in the epithelial and in the stromal compartment. The HtrA1 was significant decreased in ectopic and eutopic endometrium of women with endometriosis when compared with control endometrium in epithelial compartment. TGFb1was significantly increased in eutopic endometrium and decreased in ectopic endometrium in epithelial and stromal compartment. In addition, Ki67 was significant increased and an increase, but not significant, was detected for pSMAd2 in eutopic and ectopic endometrium compared to control one.  In summary, the significant direct correlation between TGFb1 and pSmad2 as well as between HtrA1 and TGFb1 and the very significant increase of Ki67 in stromal compartment of eutopic endometrium suggest a possible involvement of HtrA1 in the pathogenesis of endometriosis.

Natural killer cell activity in endometriosis: correlation between serum estradiol levels and cytotoxicity.

OBJECTIVE: To evaluate the correlation between natural killer cell activity and serum estradiol (E2) levels in patients with different stages of endometriosis. METHODS: Natural killer cell activity of peripheral blood lymphocytes and serum E2 levels were evaluated in 73 women who underwent laparoscopy for pelvic pain, infertility, and benign adnexal masses. RESULTS: The 33 patients (45%) with endometriosis showed a significant decrease in natural killer cell activity in relationship to an increase in disease stage (correlation coefficient r = -0.83, P < .001). A significant inverse relationship was observed between cytotoxicity and serum E2 levels (correlation coefficient r = -0.89, P < .001). CONCLUSION: The relationship between natural killer cell activity and serum E2 levels suggests that an immunoendocrine interaction plays an important role in the progression of endometriosis.

Decrease in peripheral blood polymorphonuclear leukocyte chemotactic index in endometriosis: role of prostaglandin E2 release.

OBJECTIVE: To investigate the effect of disease on peripheral blood polymorphonuclear leukocyte chemotactic index and natural killer cell cytotoxicity and to provide additional information concerning the cell-mediated immune function in endometriosis. METHODS: Chemotactic index of peripheral blood polymorphonuclear leukocytes, natural killer cell activity, and plasma estradiol (E2) and plasma prostaglandin (PG) E2 levels were evaluated in 46 women who underwent laparoscopy or laparotomy for pelvic pain, infertility, and/or benign adnexal masses. RESULTS: The 20 women (43%) with endometriosis showed a decrease in peripheral blood polymorphonuclear leukocyte chemotactic index, related to advanced disease stage (P < .001). A significant inverse correlation was observed between plasma PGE2 levels and chemotactic index in stage III and IV endometriosis (r = -.73, P = .004). Similarly, natural cytotoxicity was decreased significantly with respect to the stage of endometriosis (P = .004) and related inversely to plasma PGE2 levels (r = -.74, P = .003). A direct relationship was observed between PGE2 and plasma E2 levels (r = .59, P = .006). CONCLUSION: Advanced endometriosis is associated with decreased peripheral blood polymorphonuclear leukocyte chemotactic index and natural killer cytotoxicity, which may be related to plasma PGE2 and E2 levels.

Natural cytotoxicity and GnRH agonist administration in advanced endometriosis: positive modulation on natural killer activity.

OBJECTIVE: To investigate the effects of pharmacologic suppression of ovarian function on the immune system, with respect to the clinical outcome of endometriosis and the possibility of an immunoendocrine combined treatment. METHODS: After informed consent, 25 of 37 patients with revised American Fertility Society stage III and IV endometriosis who underwent postoperative medical treatment were selected and enrolled for this immunoendocrine longitudinal study. Medical treatment consisted of tryptorelinum depot injection, 3.75 mg/month for 24 weeks. Blood samples were collected before the first injection in the early follicular phase, day 2-3 of the cycle, and during medical treatment (every 4 weeks) and follow-up (every 6 months). At the end of the study, we had ten blood samples per patient to evaluate the cytotoxic activity, the number of natural killer cells, and the serum levels of estradiol. Natural killer activity was determined against the K562 cell line by target cell retention of the fluorescent dye carboxyfluorescein diacetate. RESULTS: A positive immunomodulating effect was observed during GnRH agonist administration. In particular, a significant progressive increase in natural killer cell activity was defined within the first 12 weeks of medical treatment; after three injections, we observed the highest values of cytotoxicity, with a median of 7.1 lytic units (range 0.3-14.0; P = .02). Natural cytotoxicity then decreased toward a plateau, which persisted during therapy completation and follow-up, with slight fluctuations. In patients who had recurrence, the values of natural killer cell activity were constantly lower than those in patients with disease-free follow-up, particularly within the first 12 weeks of medical treatment.