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Background To evaluate outcomes of laparoscopic retroperitoneal para-aortic lymphadenectomy for stage 1b3-3b cervical cancer.Methods Pathology databases searched for all para-aortic lymphadenectomy cases 2005–2016. Descriptive statistics were used to analyse baseline characteristics, cox models for treatment affect after accounting for variables, and Kaplan Meier curves for survival (STATA v15).Results 191 patients had 1b3-3b cervical cancer of which 110 patients had Para-aortic lymphadenectomy. 8 (7.3%) patients stage 1b3, 82 (74.6%) stage 2b, and 20 (18.1%) stage 3b cervical cancer. Mean lymph node count 11.7 (SD7.6). The intra-operative and post-operative 30 day complication rates were 8.8% (CI: 4.3%, 15.7%) and 5.3% (CI: 1.9%, 11.2%) respectively.Para-aortic nodes were apparently positive on CT/MRI in 5/110 (5%) cases. Cancer was found in 10 (8.9%, CI: 4.3%, 15.7%) cases on histology, all received extended field radiotherapy. Only 2 were identified on pre-operative CT/MRI imaging. 3 of 10 suspected node-positive cases on CT/MRI had negative histology. Para-aortic lymphadenectomy led to alteration in staging and radiotherapy management in 8 (8%, CI: 3.7%, 14.6%) patients. Mean overall survival 42.81 months (SD = 31.79 months). Survival was significantly higher for women undergoing PAN (50.57 (SD 30.7) months) compared to those who didn’t (31.27 (SD 32.5) months)Conclusion Laparoscopic retroperitoneal para-aortic lymphadenectomy is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.

Abstract Background Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. Methods We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls. Results Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment. Conclusions Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.

BackgroundThe impact of COVID-19 virus on menstrual cycles in unvaccinated women is limited.ObjectiveTo investigate the prevalence of changes to menstrual cycle characteristics, hormonal symptoms and lifestyle changes prior to and during the COVID-19 pandemic.MethodsA retrospective online cross-sectional survey completed by social media users between July 2020 to October 2020. Participants were living in the United Kingdom (UK), premenopausal status and, or over 18 years of age.Main outcome(s) and measures(s)The primary outcome was to assess changes to menstrual cycle characteristics during the pandemic following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Secondary outcomes included assessment of hormonal and lifestyle changes.Results15,611 social media users completed the survey. Of which, 75% of participants experienced a change in their menstrual cycle, with significantly greater proportions reporting irregular menstrual cycles (PConclusionThe COVID-19 pandemic resulted in considerable variation in menstrual cycle characteristics and hormonal symptoms. This appears to be related to societal and lifestyle changes resulting from the pandemic, rather than to the virus itself. We believe this may have an impact on the individual, as well as national economy, healthcare, and population levels, and therefore suggest this should be taken into consideration by governments, healthcare providers and employers when developing pandemic recovery plans.

BackgroundDiverticular disease of the colon represents a common clinical condition in the western world. Its prevalence increases with age and only 5% of cases occur in adults younger than 40 years of age, making it a rare condition during pregnancy. The aim of this review was to provide an overview of the reported cases of diverticulitis during pregnancy.MethodsWe conducted a systematic review of the literature based on preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. We searched three different electronic databases namely PubMed, Scopus and Web of Science from inception to December 2021. Literature search and data extraction were completed in duplicates.ResultsThe initial search yielded 564 articles from which 12 were finally included in our review. Ten articles were case reports and two were observational studies. The mean age of the cases was 34 years. The presenting complain was provided for 11 cases. The majority of the patients (10/11, 91%) presented with abdominal pain located mainly on the left (6/11, 55%) or right (4/11, 36%) iliac fossa. The most common diagnostic modality used for the diagnosis of the condition was ultrasonography in nine cases (9/12, 75%) followed by magnetic resonance imaging (MRI) in two cases (2/12, 17%). In spite of clinical and radiological evaluation, the initial diagnosis was inaccurate in seven cases (7/12, 58%). The therapeutic approach was available for 11 cases and it was based on the administration of intravenous antibiotics in six cases (6/11, 55%) and surgical management in five cases (5/11, 45%). Data for the type of delivery was provided in nine studies with five patients (5/9, 56%) delivering vaginally and four patients (4/9, 44%) delivering with cesarean section.ConclusionAs advanced maternal age becomes more common, the frequency of diverticulitis in pregnancy may increase. Although available guidelines do not exist, the clinical awareness, early recognition of the disorder, using diagnostic modalities such as ultrasound and MRI, and rapid therapeutic approach with antibiotics, may improve maternal and neonatal outcomes.

Abstract Background Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here, we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery. Methods Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery. Results The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillus spp., and Gardnerella- spp. depleted) VMB, compared with non-obese subjects (p

Persistent infection with human papillomavirus can lead to cervical intraepithelial neoplasia (CIN). Here, the authors profile the vaginal microbiota in a cohort of non-pregnant young women diagnosed with CIN2 and find that absence of Lactobacillusspp. and presence of a diverse population of strict anaerobes associates with a decreased regression of untreated CIN2 lesions.

Background: Methylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epithelial neoplasia (CIN). Methods: We performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted in duplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effects binary regression model were applied to determine pooled effect estimates. Findings: 44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamous intra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8–92·2))) vs. low-grade CIN (≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0–74·1))). Pooled difference in mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3% (95%CI:6·5–16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5–8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p

Abstract Background Local treatment for cervical intraepithelial neoplasia (CIN) by Loop Electrosurgical Excision Procedure (LEEP) has been correlated with reproductive morbidity, while the cervicovaginal microbiota is also known to affect the risk of preterm delivery. CIN and treatment by LEEP might change the cervical microbiota. The main aim of this study was to describe the cervical microbiota before and after LEEP and assess its associaton with cone depth and HPV persistence. Further, we aimed to compare the microbiota to references with normal cervical cytology. Methods Between 2005 and 2007, we prospectively identified 89 women planned for LEEP in a Norwegian hospital and recruited 100 references with a normal cervical cytology. Endocervical swabs were collected prior to treatment and at six (n = 77) and 12 months (n = 72) post LEEP for bacterial culture and PCR, and post LEEP for DNA testing for human papillomavirus (HPV). We compared the cervical microbiota composition before and after treatment and between women planned for LEEP vs references. Results There was a reduction in the number of non-Lactobacillus bacterial species six and 12 months after LEEP compared to before treatment and a tendency towards a concomitant increase in Lactobacillus. No association between the detection of cervical bacteria, HPV persistence or cone depth was found. Women planned for LEEP carried significantly more Bacteroides spp., Gardnerella vaginalis, Mycoplasma hominis and Ureaplasma parvum as well as a greater number of bacterial species than the references. Conclusions Local excisional treatment appears to alter the cervical microbiota towards a less diverse microbiota. Women with CIN have a more diverse cervical microbiota compared to women with normal cervical cytology.

Background: The introduction of high-risk human papillomavirus (hrHPV) testing as part of primary cervical screening is anticipated to improve sensitivity, but also the number of women who will screen positive. Reflex cytology is the preferred triage test in most settings but has limitations including moderate diagnostic accuracy, lack of automation, inter-observer variability and the need for clinician-collected sample. Novel, objective and cost-effective approaches are needed. Methods: In this study, we assessed the potential use of an automated metabolomic robotic platform, employing the principle of laser-assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) in cervical cancer screening. Findings: In a population of 130 women, LA-REIMS achieved 94% sensitivity and 83% specificity (AUC: 91.6%) in distinguishing women testing positive (n = 65) or negative (n = 65) for hrHPV. We performed further analysis according to disease severity with LA-REIMS achieving sensitivity and specificity of 91% and 73% respectively (AUC: 86.7%) in discriminating normal from high-grade pre-invasive disease. Interpretation: This automated high-throughput technology holds promise as a low-cost and rapid test for cervical cancer screening and triage. The use of platforms like LA-REIMS has the potential to further improve the accuracy and efficiency of the current national screening programme. Funding: Work was funded by the MRC Imperial Confidence in Concept Scheme, Imperial College Healthcare Charity, British Society for Colposcopy and Cervical Pathology, National Research Development and Innovation Office of Hungary, Waters corporation and NIHR BRC.

Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk.MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate.These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

Introduction: Histoplasmosis is a fungal infection caused by the agent Histoplasma capsulatum, a dimorphic fungus. The spectrum of illness ranges from subclinical infection to progressive disseminated disease. The major bulk of histoplasma infections are asymptomatic or pulmonary histoplasmosis. In immune compromised patients it can cause disseminated infections involving different organs of the body. In immune competent individuals it may cause isolated adrenal histoplasmosis. Material and methods: A retrospective study was done to look for mucocutaneous histoplasmosis. The excised tissue samples were cultured and only culture confirmed cases were included in the study. Result: Here, we present five cases of primary mucocutaneous histoplasmosis in immune competent individuals in a tertiary care centre in India. These patients had no other co-morbidities and had only isolated lesions in oral cavity or penis. The tissue on excision was cultured and showed growth of Histoplasma capsulatum. All the patients improved with treatment. There are limited cases of mucocutaneous ulcerated lesions caused by Histoplasma capsulatum in immune competent people in published literature. Conclusion: This study emphasizes the necessity of a vigilant look out and clinical suspicion of fungal causes like histoplasma in chronic non healing ulcers which should be confirmed by the laboratory investigations. Accurate diagnosis helps in specific management of these cases. [ABSTRACT FROM AUTHOR]