Endocervical crypt involvement by high-grade cervical intraepithelial neoplasia and its association with high-grade histopathological recurrence after cervical excision in women with negative excision margins: a systematic review and meta-analysis.

BACKGROUND: There is a growing body of evidence suggesting that endocervical crypt involvement by high-grade cervical intraepithelial neoplasia (CIN) may represent a risk factor for disease recurrence after cervical treatment. OBJECTIVES: To provide a systematic review and meta-analysis on whether endocervical crypt involvement by high-grade CIN on the excised cervical specimen is associated with high-grade histopathological recurrence during the follow-up of women after cervical excisional treatment. SEARCH STRATEGY: We searched the Medline, Scopus, Central, and Clinical Trials.gov databases from inception till May 2023. SELECTION CRITERIA: Studies that reported on women with a single cervical treatment with any method of excision for CIN2 or CIN3 lesion, negative excision margins, and whose recurrence was defined histopathologically were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated study eligibility. We used the fixed effects model for meta-analysis. MAIN RESULTS: There were 4 eligible studies included in the present systematic review that evaluated 1088 women treated with either large loop excision of the transformation zone (LLETZ) or with cold knife conization (CKC). We found no significant association of endocervical crypt involvement by CIN2-3 with high-grade histopathological recurrence at follow-up after cervical excision (OR 1.93; 95% CI 0.51-3.35). The subgroup analysis of women with LLETZ cervical excision showed again no significant association with high-grade histopathological recurrence at follow-up (OR 2.00; 95% CI 0.26-3.74). CONCLUSION: Endocervical crypt involvement by high-grade CIN does not seem to be a risk factor for high-grade histopathological recurrence after cervical excision with negative excision margins.

A High-Fat Western Diet Attenuates Intestinal Changes in Mice with DSS-Induced Low-Grade Inflammation.

BACKGROUND: A Western diet (WD) is associated with increased inflammation in the large intestine, which is often ascribed to the high dietary fat content. Intestinal inflammation in rodents can be induced by oral administration of dextran sodium sulfate (DSS). However, most studies investigating effects of WD and DSS have not used appropriate low-fat diets (LFDs) as control. OBJECTIVES: To compare the effects of a WD with those of an LFD on colon health in a DSS-induced low-grade colonic inflammation mouse model. METHODS: Six-week-old male C57BL/6JRj mice were fed an LFD (fat = 10.3% energy, n = 24) or a WD (fat = 41.2% energy, n = 24) for 15 wk [Experiment 1 (Exp.1)]. Half the mice on each diet (n = 12) then received 1% DSS in water for 6 d with the remainder (n = 12 in each diet) administered water. Disease activity, proinflammatory genes, inflammatory biomarkers, and fecal microbiota (16S rRNA) were assessed (Exp.1). Follow-up experiments (Exp.2 and Exp.3) were performed to investigate whether fat source (milk or lard; Exp.2) affected outcomes and whether a shift from LFD to WD 1 d prior to 1% DSS exposure caused an immediate effect on DSS-induced inflammation (Exp.3). RESULTS: In Exp.1, 1% DSS treatment significantly increased disease score in the LFD group compared with the WD group (2.7 compared with 0.8; P < 0.001). Higher concentrations of fecal lipocalin (11-fold; P < 0.001), proinflammatory gene expression (≤82-fold), and Proteobacteria were observed in LFD-fed mice compared with the WD group. The 2 fat sources in WDs (Exp.2) revealed the same low inflammation in WD+DSS mice compared with LFD+DSS mice. Finally, the switch from LFD to WD just before DSS exposure resulted in reduced colonic inflammation (Exp.3). CONCLUSIONS: Herein, WDs (with milk or lard) protected mice against DSS-induced colonic inflammation compared with LFD-fed mice. Whether fat intake induces protective mechanisms against DSS-mediated inflammation or inhibits establishment of the DSS-induced colitis model is unclear.

Early and late pregnancy outcomes in women treated with cold-coagulation versus LLETZ cervical treatment for cervical intraepithelial neoplasia; a retrospective cohort study.

PURPOSE: To compare the pregnancy outcomes between women who were treated with cold-coagulation versus large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia. METHODS: This was a retrospective cohort study of women who had a single cervical treatment between 2010 and 2011. We identified those women who had a singleton pregnancy subsequent to their cervical treatment until September 2017. Women with previous cervical treatment, previous miscarriage or preterm delivery were excluded. RESULTS: We identified 86 women with a pregnancy after LLETZ treatment and 75 women after cold coagulation. Those who had LLETZ when compared to cold coagulation miscarried more often in the first trimester (33.7 vs 17.3%; p = 0.01) than in the second trimester. In women with LLETZ this effect of increased early miscarriage was shown to be prolonged and to persist up to 17 months after excision. Women with LLETZ when compared to cold coagulation had higher spontaneous preterm birth rates (8.9 vs 6.7%) even though the difference was non significant, with the earliest spontaneous preterm birth occurring at 32 weeks and 34 weeks, respectively. CONCLUSION: We found that women who received LLETZ treatment when compared to cold coagulation had higher spontaneous preterm birth rates in their subsequent pregnancy and miscarried more frequently in the first trimester, and demonstrated an increased early miscarriage risk that persisted for more than a year after excisional treatment.

Comparison of cure rates in women treated with cold-coagulation versus LLETZ cervical treatment for CIN2-3 on pretreatment cervical punch biopsies: a retrospective cohort study.

PURPOSE: To compare the cure rates between women who were treated with cold-coagulation versus large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia grade 2 (CIN2) or 3 (CIN3) on pretreatment cervical punch biopsies. METHODS: This was a retrospective cohort study of women having had a single cervical treatment for CIN2 or CIN3 on pretreatment cervical punch biopsies between 2010 and 2011. The cure rates were defined as the absence of any dyskaryosis (mild/moderate/severe) on cytology tests during follow-up and were determined at 6 and 12 months after treatment. RESULTS: We identified 411 women having had cervical treatment with 178 cases of cold-coagulation and 233 cases of LLETZ. The cure rates at 6 months following cold-coagulation and LLETZ treatment were 91.6 versus 97.1% (p = 0.02), whereas at 12 months, they were 96.5 versus 97.3% (p = 0.76). Multivariable analysis showed that after adjusting for confounding factors, there was a fourfold higher cure rate with LLETZ in comparison with cold-coagulation at 6 months after treatment (adjusted OR 4.50, 95% CI 1.20-16.83; p = 0.026), with this difference disappearing at 12 months. The lower cure rates with cold-coagulation were due to its higher rates of mild dyskaryosis cytology tests at 6 months. The rates of moderate/severe dyskaryosis cytology tests were similar between the two treatment methods at 6 and 12 months. CONCLUSION: We found that women with CIN2 or CIN3 on pretreatment cervical punch biopsies, after adjusting for multiple confounding factors, had higher cure rates when treated with LLETZ versus cold-coagulation at 6 months, with this difference disappearing at 12 months.

The SaTH risk-assessment tool for the prediction of emergency cesarean section in women having induction of labor for all indications: a large-cohort based study.

PURPOSE: To develop a risk-assessment model for the prediction of emergency cesarean section (CS) in women having induction of labor (IOL). METHODS: This was an observational cohort study of women with IOL for any indication between 2007 and 2013. Women induced for stillbirths and with multiple pregnancies were excluded. The primary objective was to identify risk factors associated with CS delivery and to construct a risk-prediction tool. RESULTS: 6169 women were identified with mean age of 28.9 years. Primiparity involved 47.1 %, CS rate was 13.3 % and post-date pregnancies were 32.4 %. Risk factors for CS were: age >30 years, BMI >25 kg/m2, primiparity, black-ethnicity, non post-date pregnancy, meconium-stained liquor, epidural analgesia, and male fetal gender. Each factor was assigned a score and with increasing scores the CS rate increased. The CS rate was 5.4 % for a score <11, while for a score ≥11 it increased to 25.0 %. The model had a sensitivity, specificity, negative predictive value and positive predictive value of 75.8, 65.1, 93.8 and 25.0 %, respectively. CONCLUSION: We have constructed a risk-prediction tool for CS delivery in women with IOL. The risk-assessment tool for the prediction of emergency CS in induced labor has a high negative-predictive value and can provide reassurance to presumed low-risk women.

The incidence of and risk factors for a repeat obstetric anal sphincter injury (OASIS) in the vaginal birth subsequent to a first episode of OASIS: a hospital-based cohort study.

PURPOSE: To identify the incidence of and risk factors for a repeat obstetric anal sphincter injury (OASIS) in women who sustained an OASIS in their first vaginal delivery and have a subsequent vaginal birth. METHODS: Data were collected retrospectively for women having had singleton cephalic presentation vaginal deliveries between 2007 and 2015. Women with breech deliveries, stillbirths, foetal congenital abnormalities and multiple pregnancies were excluded. RESULTS: Over the study period, we identified 11,191 women who had a first vaginal birth, of which 603 (5.4%) sustained a first episode of OASIS. Of these women, 243 (40.2%) had a subsequent pregnancy with 190 (78.1%) having a second vaginal birth, 13 (5.4%) an emergency caesarean section (CS) delivery while in labour and 40 (16.5%) an elective CS delivery. In those who delivered vaginally, 16 (8.4%) women had a repeat OASIS. After adjusting for several confounding factors, it was found that the risk of a repeat OASIS was associated with the use of epidural analgesia (OR = 3.66; 95% CI: 1.14-11.71) and an episiotomy in the first delivery (OR = 3.93; 95% CI:1. 03-15.02) and a short labour (<2.8 h) in the second delivery (OR = 14.55; 95% CI: 1.83-115.75). The time interval between the two vaginal births was not associated with any increased risk of a repeat OASIS. CONCLUSION: We found that 8.4% of women sustained a repeat OASIS in a subsequent vaginal birth with this risk being associated with the presence of a short second labour and certain features from the first labour.

Vestibular Mast Cell Density in Vulvodynia: A Case-Controlled Study.

OBJECTIVES: To identify whether mast cell densities in vulvar biopsies from the vestibule are associated with vulvodynia. METHODS: We enrolled 100 women aged 19 to 59 years with confirmed vulvodynia cases, 100 racially matched controls, and 100 black control women. All had vulvar biopsies performed at the 7 o'clock position of the vestibule, which were then immunostained to detect c-KIT protein. The numbers of c-KIT positive mast cells per ×400 magnification field were manually counted, and t tests and logistic regression were used to assess the association with case-control status. RESULTS: Of the biopsies, 235 were adequate samples for c-KIT testing for mast cells. The mast cell density was substantially lower in black control women (13.9 ± 10.9) in comparison to white control women (22.5 ± 13.2 p < 0.001): hence the analysis was confined to white cases and racially matched control women. Compared with racially matched controls, cases were younger, more likely to be married, and reported a higher household income. The average number of mast cells per ×400 magnification field overall was 19.1 ± 13.2 (range, 0-62). There was no difference in the mast cell count between racially matched cases (22.4 ± 13.9 per ×400 field) and controls (22.5 ± 13.2) in either the univariate or multivariable analyses. Within the group of cases, there was no difference in mast cell density based on the presence or absence of a variety of urogenital symptoms. CONCLUSIONS: No difference in mast cell density in biopsies of the vestibule was found between white cases and racially matched controls. Black control women have a lower mast cell density compared with white control women.

Perineal support and risk of obstetric anal sphincter injuries: a Delphi survey.

OBJECTIVE: To explore the views of a multidisciplinary group of experts and achieve consensus on the importance of perineal support in preventing obstetric anal sphincter injuries (OASIS). DESIGN: A three-generational Delphi survey. SETTING: A UK-wide survey of experts. POPULATION: A panel of 20 members consisting of obstetricians, midwives and urogynecologists recommended by UK professional bodies. METHODS: A 58-item web-based questionnaire was sent to all participants who were asked to anonymously rate the importance of each item on a six-point Likert scale. They were asked to rate their level of agreement on statements related to hands-on/hands-poised techniques, the association of hands-poised/hands-off approach with OASIS, the need to implement perineal support and the need to improve the evidence to support it. Systematic feedback of responses from previous rounds was provided to participants. MAIN OUTCOME MEASURES: To achieve consensus on key areas related to perineal support. RESULTS: The response rate was 100% in all three iterations. There was consensus that current UK practice regarding perineal protection was not based on robust evidence. The respondents agreed that hands-poised/hands-off and OASIS are causally related and that hands-poised was misinterpreted by clinicians as hands-off. Although 90% of experts agreed that some form of randomized trial was required and that all would be prepared to take part, there was also consensus (75%) that in the meantime, hands-on should be the recommended technique. CONCLUSIONS: Our results highlight the current lack of evidence to support policies of perineal support at time of birth and the need to address this controversial issue.

Risk factors for treatment failure following cold coagulation cervical treatment for CIN pathology: a cohort-based study.

PURPOSE: To determine any risk factors for cytology recurrence in women after cold coagulation ablative treatment for cervical intraepithelial neoplasia (CIN). METHODS: This was a retrospective observational study of a cohort of women having had cold coagulation between 2001 and 2011 in the colposcopy unit of an NHS hospital. We retrospectively collected data from our colposcopy unit database. Women with previous cervical treatment were excluded. RESULTS: 559 eligible women were identified with a mean age of 28.7 ± 6.2 years. Nulliparous women were 66.3 % with smokers involving 35.3 %. Referral cytology, pretreatment cervical punch biopsies and colposcopy were high grade in 51.9, 71.9 and 45.8 % of women. Endocervical crypt involvement (ECI) on pretreatment cervical punch biopsy involved 9.7 % of women. Mean follow-up was 3.1 ± 2.4 years. Overall cytology recurrence (mild/moderate/severe dyskaryosis) at 6 and 12 months follow-up was 7.4 and 5 %. High-grade cytology recurrence (moderate/severe dyskaryosis) involved 2.7 % of women over the entire follow-up period. Multiple regression analysis showed that ECI on pretreatment cervical punch biopsy was a risk factor for high-grade cytology recurrence (HR 3.72; 95 %CI 1.18-11.71; p = 0.024). There were no risk factors identified for overall cytology recurrence. However, when cytology tests with borderline nuclear changes at follow-up were pooled with mild/moderate/severe dyskaryosis cytology tests, then parity ≥2 was a risk factor for abnormal cytology (HR 1.71; 95 %CI 1.08-2.69; p = 0.022). CONCLUSIONS: Endocervical crypt involvement on pretreatment cervical punch biopsy and multiparity ≥2 are risk factors that increase the likelihood of abnormal cytology following cold coagulation. These two risk factors should be taken in consideration when performing cold coagulation cervical treatment for CIN pathology.

Endocervical Crypt Involvement by CIN2-3 as a Predictor of Cytology Recurrence After Excisional Cervical Treatment.

OBJECTIVE: The primary objective was to determine whether endocervical crypt involvement (ECI) by cervical intraepithelial neoplasia (CIN) on the excised cervical tissue after large loop excision of the transformation zone (LLETZ) represents a predictor of cytology recurrence. Secondary objective was to identify the ability of a pretreatment cervical punch biopsy to predict cytology recurrence. MATERIALS AND METHODS: This was a case series study conducted in an NHS hospital. Women with LLETZ treatment performed over a 2-year period (2010-2011) were identified through our colposcopy database. Women with previous cervical treatment, cervical cancer on cone histopathology, or missing follow-up data were excluded. RESULTS: A group of 526 eligible women was identified over the study period. Crypt involvement was not a predictor of recurrence in the total sample. However, in the subgroup of women with CIN2-3 on pretreatment punch biopsy and with ECI on cone specimen in comparison to those without ECI, we identified an increased risk for overall cytology recurrence (HR, 3.1; 95% CI, 1.04-9.28; P = 0.043) and a trend for increased risk of high-grade cytology recurrence (HR, 4.62; 95% CI, 0.84-25.28; P = 0.07). A pretreatment punch biopsy showing crypt involvement by CIN2-3 was indicative of women at risk for abnormal cytology after excision. In women with CIN2-3 on pretreatment punch biopsy and ECI on excised tissue, the high-grade cytology recurrence was significantly reduced if more than 1.9 cm of cervix was removed. CONCLUSIONS: It seems that the presence of crypt involvement on the excised cervix in the subgroup of women with CIN2-3 on pretreatment punch biopsy is predictive of cytology recurrence.

A rare case of Asherman's syndrome after open myomectomy: sonographic investigations and possible underlying mechanisms.

AIMS: To present a study on severe Asherman's syndrome after open myomectomy and investigate the possible reasons for this outcome. METHODS: This study involves a rare case of a 38-year-old nulliparous woman who underwent a relatively minor and straightforward open myomectomy in a university hospital setting, during which the uterine cavity was not entered and there were no post-operative complications. Post-operatively the patient had oligomenorrhoea for over a year. The patient was investigated with three-dimensional power Doppler angiography of the uterus and underwent diagnostic/operative hysteroscopy. Main outcome measures were to sonographically assess the blood flow and vascularisation throughout the uterus and to hysteroscopically confirm diagnosis of Asherman's syndrome and treat the patient at the same time. RESULTS: Sonographically there was reduced perfusion in the outer part of the uterus and the scarred areas of the endometrium. Upon hysteroscopic confirmation of diagnosis, the division of adhesions led to a normal sized uterine cavity. CONCLUSIONS: Among the predisposing and causal factors that have been implicated in post-operative adhesion formation, endometrial trauma, infection and tissue hypoxia are considered the most important. This case supports a role for tissue hypoxia in the development of Asherman's syndrome after open myomectomy.

The improvement and retention of skills in shoulder dystocia management with the use of high-fidelity simulation: The SAFE (SimulAtion high-FidElity) study.

BACKGROUND: Shoulder dystocia is a relatively uncommon but serious childbirth-related emergency. AIM: To explore the improvement and retention of skills in shoulder dystocia management through high-fidelity simulation training. METHODS: The SAFE (SimulAtion high-FidElity) study was a prospective cohort study that utilised a high-fidelity birth simulator. Registered midwives and final year midwifery students were invited to participate in a one-day workshop at 6-monthly intervals. There was a 30-minute initial assessment, a 30-minute theoretical and hands-on training, and a 30-minute post-training assessment on shoulder dystocia management. Pre-training and post-training values for the predetermined outcomes were compared. In each workshop we assessed the proportion of successful simulated births, the performance of manoeuvres to manage shoulder dystocia, the head-to-body birth time, the fetal head traction force, the quality of communication, the perception of time-to-birth, and the self-reported confidence levels. FINDINGS: The baseline workshop recruited 101 participants that demonstrated a significant increase in the proportion of successful simulated births (8.9% vs 93.1%), and a two-fold to three-fold increase in the score of manoeuvres, communication, and confidence after training. Those with low pre-training levels of competency and confidence improved the most post-training at baseline. There was a retention of manoeuvres, communication skills and confidence at 6 months. There was no reduction in fetal head traction force over time. Those being proficient before initial training retained and performed best at the 6-month follow-up. CONCLUSION: The SAFE study found a significant improvement in skills and confidence after the initial high-fidelity simulation training that were retained after 6 months.

Appropriate cone dimensions to achieve negative excision margins after large loop excision of transformation zone in the uterine cervix for cervical intraepithelial neoplasia.

AIMS: To determine appropriate cone dimensions for predicting margin status after large loop excision of transformation zone (LLETZ) treatment. METHODS: An observational study performed at the Colposcopy Unit of a university hospital setting involving patients who underwent LLETZ conisation within a 1-year period. Data concerning the characteristics, cone dimensions, lesion grade and excision margins of the patients were recorded. RESULTS: The median age of the women (n = 61) was 38 years (18-53). LLETZ cone specimens had 36.1% of cervical intraepithelial neoplasia (CIN)2/3 lesion and 13.1% positive margins. Mean cone depth and volume were 10.9 mm and 2.3 cm(3), respectively. Multiple logistic regression for main predictors and after adjustment for age, parity and CIN severity showed that cone volume and length, cone base surface and proportion of excised volume had a significant effect on margin positivity. ROC analysis showed that optimal cut-off for cone volume was 2.1 cm(3) (87.5% sensitivity - 54.7% specificity) or 8.6% of initial cervical volume (75% sensitivity - 75.5% specificity), and for cone length it was 10 mm (100% sensitivity - 52.8% specificity). Optimal cut-off for cone base surface as percentage of ectocervical surface was 32.7% (75% sensitivity - 69.8% specificity). CONCLUSIONS: These findings should be taken into consideration when planning the outer boundaries of excision and cervical tissue to be removed so as to achieve oncologically safe limits.

The purple line and its association with cervical dilatation in labour: A systematic review and meta-analysis.

BACKGROUND: There is a growing body of evidence that the presence and length of the purple line could represent a non-invasive method of estimating and determining labour progress. OBJECTIVES: The primary outcome was to provide a systematic review and meta-analysis on the association between the purple line length and cervical dilatation in active labour. The secondary outcome was to determine the association between the purple line length and the fetal head descent, and to calculate the pooled mean length of the purple line at a cervical dilatation of 3-4 cm and at a cervical dilatation of 9-10 cm. SEARCH STRATEGY: We searched the Medline, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Clinical Trials.gov and Cochrane Pregnancy and Childbirth's Trials Register databases from inception till March 25, 2023. SELECTION CRITERIA: We included observational studies of pregnant women in active first stage of labour who had their labour progress assessed with the use of regular vaginal examinations and who had the occurrence recorded and length of the purple line measured at the same time. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated study eligibility. We used the random effects and fixed effects model for meta-analysis. MAIN RESULTS: There were six eligible studies included in the systematic review that reported on 982 women in total with the purple line appearing in 760 (77.3%) of cases. We found a moderate positive pooled correlation between the purple line length with cervical dilatation (r = +0.64; 95%CI: 0.41-0.87) and fetal head descent (r = +0.50; 95%CI: 0.32-0.68). For women either in spontaneous or induced labour, the pooled mean length of the purple line was more than 9.4 cm when the cervical dilatation was 9-10 cm, whereas it was more than 7.3 cm when the cervical dilatation was 3-4 cm. CONCLUSIONS: The purple line is a non-invasive method that may potentially be used as an adjunct in labour progress assessment.