Publications
243 results found
Kyrgiou M, Kalliala I, Markozannes G, et al., 2017, Adiposity and cancer at all anatomic sites: an umbrella review of the literature, British Medical Journal, Vol: 356, Pages: 1-10, ISSN: 1468-5833
Objective: Although meta-analyses support associations between obesity and several cancers, some of the claimed associations may be flawed due to inherent biases. We evaluated strength and validity of the evidence for adiposity and risk of cancer development and mortality using an umbrella review methodology.Methods:Design: An umbrella review of systematic reviews and meta-analyses.Data sources: PubMed, EMBASE, Cochrane database of systematic reviews and manual screening. Eligibility criteria for selecting studies: Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer. Main Outcomes: Primary analysis focused on cohort studies exploring associations for continuous contrasts of adiposity. Data synthesis: The evidence was graded into strong, highly suggestive, suggestive or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, between-study heterogeneity, 95% prediction intervals, small study effects, excess significance bias and sensitivity analysis with credibility ceilings.Results: 204 meta-analyses investigated associations between seven indices of adiposity and the development or death from 36 primary cancers and their sub-types. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, 12 (13%) associations for nine cancers demonstrated strong evidence. Elevated BMI was associated with a higher risk of developing oesophageal adenocarcinoma, colon and rectal cancer in men, biliary tract, pancreatic, endometrial cancer in pre-menopausal women, kidney cancer and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with a higher risk of post-menopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectivel
Kottaridi C, Kyrgiou M, Pouliakis A, et al., 2017, Quantitative measurement of L1 HPV16 methylation for the prediction of pre-invasive and invasive cervical disease, Journal of Infectious Diseases, Vol: 215, Pages: 764-771, ISSN: 1537-6613
Background: Methylation of the HPV DNA has been proposed as a novel biomarker. Here, we correlated the mean methylation level of 12 CpG sites within L1 gene, to the histological grade of cervical precancer and cancer. We assessed whether HPV L1 gene methylation can predict the presence of high-grade disease at histology in women testing positive for HPV 16 genotype. Methods: Pyrosequencing was used for DNA methylation quantification and 145 women were recruited. Results: We found that the L1 HPV16 mean methylation (+/-SD) significantly increased with disease severity [CIN3=17.9%(±7.2) vs CIN2=11.6%(±6.5), p<0.001 or vs CIN1 =9.0%(±3.5), p<0.001). Mean methylation was a good predictor of CIN3+ cases; the Area Under the Curve (AUC) was higher for sites 5611 in the prediction of CIN2+ and higher for position 7145 for CIN3+. The evaluation of different methylation thresholds for the prediction of CIN3+, showed that the optimal balance of sensitivity and specificity (75.7% and 77.5%, respectively), PPV and NPV (74.7% and 78.5%, respectively) was achieved for a methylation of 14.0% with overall accuracy of 76.7%. Conclusion: Elevated methylation level is associated with increased disease severity and has good ability to discriminate HPV16 positive women that have high-grade disease or worse.
Kyrgiou M, Kalliala I, Mitra A, et al., 2017, Immediate referral to colposcopy versus cytological surveillance for minor cervical cytological abnormalities in the absence of HPV test, Cochrane Database of Systematic Reviews, Vol: 1, ISSN: 1469-493X
BackgroundA significant number of women are diagnosed with minor cytological abnormalities on cervical screening. Many authorities recommendsurveillance as spontaneous regression might occur. However,attendance for cytological follow-up decreases with time and might putsome women at risk of developing invasive disease.ObjectivesTo assess the optimum management strategy for women with minor cervical cytological abnormalities (atypical squamous cells ofundetermined significance - ASCUS or low-grade squamous intra-epithelial lesions - LSIL) at primary screening in the absence of HPV(human papillomavirus) DNA test.Search methodsWe searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 2016), MEDLINE,and Embase from inception to 21 April 2016.Selection criteriaWe included randomised controlled trials (RCTs) comparing immediate colposcopy to cytological surveillance in women with atyp-ical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/milddyskaryosis).Data collection and analysisThe primary outcome measure studied was the occurrence of cervicalintra-epithelial neoplasia (CIN). The secondary outcome measuresstudied included default rate, clinically significant anxiety and depression, and other self-reported adverse effects.We classified studies according to period of surveillance, at 6, 12, 24 or 36 months, as well as at 18 months, excluding a possibleexit-examination. We calculated pooled risk ratios (RR) and 95%confidence intervals (CI) using a random-effects model with inversevariance weighting. Inter-study heterogeneity was assessedwith I2statistics.Main resultsWe identified five RCTs with 11,466 participants that fulfilledthe inclusion criteria. There were 18 cases of invasive cervical cancer,seven in the immediate colposcopy and 11 in the cytological surveillance groups, respectively. Although immediate colposcopy detectsCIN2+ and CIN3+ earlier
Domenici L, Nixon K, Sorbi F, et al., 2017, Surgery for Recurrent Uterine Cancer: Surgical Outcomes and Implications for Survival-A Case Series, International Journal of Gynecological Cancer, Vol: 27, Pages: 759-767, ISSN: 1525-1438
OBJECTIVE: The purpose of this study was to describe the patterns of relapse in uterine cancer (UC) and the role of surgery in the recurrent setting. METHODS: We describe surgical and clinical outcomes of all patients who underwent surgery for recurrent UC in a gynecological oncology tertiary referral center between May 1, 2013, and April 30, 2016. Progression-free survival and overall survival were estimated using Kaplan-Meier methods with the surgery at relapse being the starting point. RESULTS: We evaluated 15 patients with a median age of 66 years. The predominant histology was the endometrioid variant (n = 11; 73.3%). The median interval between the end of previous treatment and relapse surgery was 24 months (range, 8-164). Locoregional pelvic recurrences were the most common type of recurrence (n = 13; 86.7%) with the para-aortic lymph node space being the most commonly affected extrapelvic site (13%). Patients predominantly presented with a multifocal pattern of relapse (n = 10; 66.7%) requiring multivisceral resections such as bowel (n = 7; 46.6%) and/or bladder/ureteric resections (n = 8; 53.3%) to achieve complete tumor clearance. All patients were operated tumor free with a 30-day major morbidity and mortality rate of 6.7% and 0%, respectively. Five patients (33.3%) received postoperative chemotherapy or radiotherapy. Five patients (33.3%) relapsed, and 3 died within a mean follow-up of 12.4 months (95% confidence interval [CI], 6.5-18.2). Two of those patients had a sarcoma.Mean progression-free survival and overall survival for the entire cohort postrelapse surgery was 21.7 months (95%CI, 13.9-29.5) and 26.0 months (95%CI, 18.4-33.7), respectively. Survival was significantly worse in patients with nonendometrioid histology (P < 0.0001). CONCLUSIONS: Surgery for UC relapse seems feasible with acceptable morbidity and high complete resection rates despite the multifocal patterns of relapse in a selected group of patients in a reference center for gynec
Kyrgiou M, 2016, Tracking the impact of excisional cervical treatment on the cervix using biospectroscopy, Scientific Reports, Vol: 6, ISSN: 2045-2322
Local excisional treatment for cervical intra-epithelial neoplasia (CIN) is linked to significant adverse sequelae including preterm birth, with cone depthand radicality of treatment correlatingto the frequency and severity of adverse events. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy can detect underlying cervical disease more accurately than conventional cytology. The chemical profile of cells pre-and post-treatment may differas a result of altered biochemical processes due to excision,or treatment of the disease.Since pre-treatment cervicallength variesamongst women, the percentage of cervix excised may correlate more accurately to riskthan absolute dimensions. We show that treatment for CIN significantly altersthe biochemistry ofthe cervix, compared with women who have not had treatment; this is due to the excision of cervical tissue rather thana disease-controlling effect. However, the spectra do seem to correlate to the cone depth or proportion of cervical length excised.Future research should aim to explore the impact of treatment in a larger cohort.
Mitra A, Paraskevaidis M, Lai J, et al., 2016, Reduction in antimicrobial peptides after excisional treatment for cervical intraepithelial neoplasia: a possible mechanism of subsequent preterm birth?, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 123, Pages: E11-E11, ISSN: 1470-0328
Paraskevaidi M, Martin-Hirsch PL, Kyrgiou M, et al., 2016, Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research, Mutagenesis, Vol: 32, Pages: 335-342, ISSN: 1464-3804
Mitochondrial diseases have been extensively investigated over the last three decades, but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases but also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat, as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease. Special attention is given to the influence of xenobiotics on mitochondria; environmental factors inducing mutations or epigenetic changes in the mitochondrial genome can alter its expression and impair the whole cell’s functionality. Specifically, we suggest that environmental agents can cause damage in mitochondrial DNA and consequently lead to mutagenesis. Moreover, we describe current approaches for handling mitochondrial diseases, as well as available prenatal diagnostic tests, towards eliminating these maternally inherited diseases. Undoubtedly, more research is required, as current therapeutic approaches mostly employ palliative therapies rather than targeting primary mechanisms or prophylactic approaches. Much effort is needed into further unravelling the relationship between xenobiotics and mitochondria, as the extent of influence in mitochondrial pathogenesis is increasingly recognised.
Kindinger LM, Kyrgiou M, MacIntyre DA, et al., 2016, Preterm Birth Prevention Post-Conization: A Model of Cervical Length Screening with Targeted Cerclage, PLOS One, Vol: 11, ISSN: 1932-6203
Women with a history of excisional treatment (conization) for cervical intra-epithelial neoplasia (CIN) are at increased risk of preterm birth, perinatal morbidity and mortality in subsequent pregnancy. We aimed to develop a screening model to effectively differentiate pregnancies post-conization into low- and high-risk for preterm birth, and to evaluate the impact of suture material on the efficacy of ultrasound indicated cervical cerclage. We analysed longitudinal cervical length (CL) data from 725 pregnant women post-conization attending preterm surveillance clinics at three London university Hospitals over a ten year period (2004–2014). Rates of preterm birth <37 weeks after targeted cerclage for CL<25mm were compared with local and national background rates and expected rates for this cohort. Rates for cerclage using monofilament or braided suture material were also compared. Of 725 women post-conization 13.5% (98/725) received an ultrasound indicated cerclage and 9.7% (70/725) delivered prematurely, <37weeks; 24.5% (24/98) of these despite insertion of cerclage. The preterm birth rate was lower for those that had monofilament (9/60, 15%) versus braided (15/38, 40%) cerclage (RR 0.7, 95% CI 0.54 to 0.94, P = 0.008). Accuracy parameters of interval reduction in CL between longitudinal second trimester screenings were calculated to identify women at low risk of preterm birth, who could safely discontinue surveillance. A reduction of CL <10% between screening timepoints predicts term birth, >37weeks. Our triage model enables timely discharge of low risk women, eliminating 36% of unnecessary follow-up CL scans. We demonstrate that preterm birth in women post-conization may be reduced by targeted cervical cerclage. Cerclage efficacy is however suture material-dependant: monofilament is preferable to braided suture. The introduction of triage prediction models has the potential to reduce the number of unnecessary CL scan for women at low risk of
Kyrgiou M, Mitra A, Paraskevaidis E, 2016, Fertility and early pregnancy outcomes following conservative treatment for cervical intraepithelial neoplasia and early cervical cancer, JAMA Oncology, Vol: 2, Pages: 1496-1498, ISSN: 2374-2445
Clinical Question: Does local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer adversely affect successful conception and early pregnancy outcomes in the first and second trimester (<24 weeks of gestation)? Clinical Application: Local cervical treatment does not adversely affect fertility or first trimester miscarriage, although it is associated with a significant increase in the risk of second trimester miscarriages.
Mitra A, Macintyre DA, marchesi, et al., 2016, The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?, Microbiome, Vol: 4, ISSN: 2049-2618
The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon analysis of bacterial 16S rRNA genes permits in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture based microbiological techniques. The Human Papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence, and the development of cervical precancer and cancer. In this review we summarise the current literature, and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.
Kyrgiou M, Athanasiou A, Paraskevaidi M, et al., 2016, Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. Editorial Comment, Obstetrical & Gynecological Survey, Vol: 71, Pages: 646-648, ISSN: 1533-9866
Local cervical treatment for preinvasive cervical disease such as cervical intraepithelial neoplasia (CIN) has been associated with an increased risk of preterm birth, perinatal morbidity, and mortality in a later pregnancy. This meta-analysis aimed to investigate the impact of treatment for cervical preinvasive and early invasive disease on obstetric outcomes and to see how this risk could be modified by the cone depth and comparison group.
Mitra A, MacIntyre D, Lee Y, et al., 2016, Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity, Blair Bell Research Society Annual Academic Meeting, Publisher: Wiley, Pages: E11-E12, ISSN: 1470-0328
Kyrgiou M, Mitra A, Athanasiou A, et al., 2016, The risk of preterm birth after treatment for cervical pre-invasive and early invasive disease increases with increasing cone depth: a systematic review and meta-analysis, Blair Bell Research Society Annual Academic Meeting, Publisher: Wiley, Pages: E8-E8, ISSN: 1470-0328
Kyrgiou M, Kalliala I, Mitra A, et al., 2016, Immediate referral to colposcopy vs. cytological surveillance for low-grade cervical cytological abnormalities in the absence of HPV test: A systematic review and a meta-analysis of the literature, International Journal of Cancer, Vol: 140, Pages: 216-223, ISSN: 1097-0215
We performed a systematic review and meta-analysis to explore the optimum management strategy for women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/mild dyskaryosis) cytological abnormalities at primary screening in the absence of HPV DNA test. We searched MEDLINE, EMBASE and CENTRAL and included randomised controlled trials comparing immediate colposcopy to cytological surveillance in women with ASCUS/LSIL. The outcomes of interest were occurrence of different histological grades of cervical intra-epithelial neoplasia (CIN) and default rates during follow-up. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect model and with inverse variance weighting. Interstudy heterogeneity was assessed using I2 statistics. Six RCTs were included. Immediate colposcopy significantly increased detection of unimportant abnormalities as opposed to repeat cytology (koilocytosis:32% vs.21%, RR:1.49, 95%CI=1.17-1.90); CIN1:21% vs.8%, RR:2.58, 95%CI=1.69-3.94). Although immediate colposcopy detected CIN2, CIN2+ and CIN3+ earlier than cytology, the differences were no longer observed at 24 months (CIN3+:10.3 vs.11.9%, RR:1.02, 95%CI=0.53-1.97), with significant inters-study heterogeneity (p<0.001,I2=93%). Default risk was significantly higher for repeat cytology (6months: 6.3 vs.13.3%, RR:3.85, 95%CI=1.27-11.63; 12months: 6.3 vs.14.8%, RR:6.39, 95%CI=1.24-32.95; 24 months: 0.9 vs.16.1%, RR:19.1,95%CI=9.02-40.4). Detection of CIN2+ for cytological surveillance over two years is similar to that of immediate colposcopy, although patients may default. Colposcopy may be first choice when good compliance is not assured, but may increase detection of insignificant lesions. This emphasizes the need for a reflex triage test to distinguish women who need diagnostic work-up from those who can return to routine recall.
Nasser S, Lazaridis A, Evangelou M, et al., 2016, Correlation of pre-operative CT findings with surgical & histological tumor dissemination patterns at cytoreduction for primary advanced and relapsed epithelial ovarian cancer: A retrospective evaluation, Gynecologic Oncology, Vol: 143, Pages: 264-269, ISSN: 1095-6859
ObjectivesComputed tomography (CT) is an essential part of preoperative planning prior to cytoreductive surgery for primary and relapsed epithelial ovarian cancer (EOC). Our aim is to correlate pre-operative CT results with intraoperative surgical and histopathological findings at debulking surgery.MethodsWe performed a systematic comparison of intraoperative tumor dissemination patterns and surgical resections with preoperative CT assessments of infiltrative disease at key resection sites, in women who underwent multivisceral debulking surgery due to EOC between January 2013 and December 2014 at a tertiary referral center. The key sites were defined as follows: diaphragmatic involvement(DI), splenic disease (SI), large (LBI) and small (SBI) bowel involvement, rectal involvement (RI), porta hepatis involvement (PHI), mesenteric disease (MI) and lymph node involvement (LNI).ResultsA total of 155 patients, mostly with FIGO stage IIIC disease (65%) were evaluated (primary = 105, relapsed = 50). Total macroscopic cytoreduction rates were: 89%. Pre-operative CT findings displayed high specificity across all tumor sites apart from the retroperitoneal lymph node status, with a specificity of 65%.The ability however of the CT to accurately identify sites affected by invasive disease was relatively low with the following sensitivities as relating to final histology:32% (DI), 26% (SI), 46% (LBI), 44% (SBI), 39% (RI), 57% (PHI), 31% (MI), 63% (LNI).ConclusionPre-operative CT imaging shows high specificity but low sensitivity in detecting tumor involvement at key sites in ovarian cancer surgery. CT findings alone should not be used for surgical decision making.
Mitra A, Kindinger L, Kalliala I, et al., 2016, Obstetric complications after treatment of cervical intraepithelial neoplasia, British Journal of Hospital Medicine, Vol: 77, Pages: C124-C127, ISSN: 1750-8460
Mitra A, Tzafetas M, Lyons D, et al., 2016, Cervical intraepithelial neoplasia: screening and management., British Journal of Hospital Medicine, Vol: 77, Pages: C118-C123, ISSN: 1750-8460
Globally, cervical cancer remains the fourth most common female malignancy, with over 528 000 new cases and 266 000 deaths in 2012; 84% of these occurred in low-resource settings (Ferlay et al, 2015). Cervical cancer is largely preventable through organized screening programmes, which can detect pre-malignant disease and treat it before invasive disease develops. Cervical intraepithelial neoplasia is the pre-malignant, dysplastic condition of the uterine cervix, which in a small proportion of cases will eventually progress to invasive cervical cancer if left untreated.
Kyrgiou M, Athanasiou A, Paraskevaidi M, et al., 2016, Adverse obstetrical outcomes after local treatment for cervical pre-invasive and early invasive disease according to the cone depth: a systematic review and meta-analysis, BMJ, Vol: 354, Pages: 1-15, ISSN: 0959-8138
Objective: To assess the effect of treatment for CIN on obstetric outcomes and to correlate this to the cone depth and comparison group used.MethodsDesign: Systematic review and meta-analysisData Sources: CENTRAL, MEDLINE, EMBASE from 1948 to April 2016.Eligibility Criteria: Studies assessing obstetric outcomes in women with or without a previous local cervical treatment.Data Extraction & Synthesis: Independent reviewers extracted the data and performed quality assessment using the Newcastle-Ottawa criteria. Studies were classified according to method and obstetric endpoint. Pooled risk ratios (RR) were calculated using a random-effect model and inverse variance. Inter-study heterogeneity was assessed with I2 statistics.Main outcomes and measures: Obstetric outcomes; preterm birth (PTB) (spontaneous and threatened), premature rupture of the membranes (pPROM), chorioamnionitis, mode of delivery, length of labour, induction of delivery, oxytocin use, haemorrhage, analgesia, cervical cerclage & cervical stenosis. Neonatal outcomes; low birth weight (LBW), neonatal intensive care unit (NICU) admission, stillbirth, APGAR scores and perinatal mortality.Results: Seventy-one studies were included (6338982 participants: 65082 treated-6292563 untreated). Treatment significantly increased the risk of overall (<37weeks)(10.7 v 5.4%, RR=1.78[1.60 to 1.98]), severe (<34/32weeks)(3.5 v 1.4%, RR=2.40[1.92 to 2.99]) and extreme (<30/28weeks)(1.0 v 0.3%, RR=2.54[1.77 to 3.63]) PTB. The magnitude of the effect was higher for techniques removing or ablating more tissue (<37weeks: CKC (RR=2.70[2.14 to 3.40]), LC (RR=2.11[1.26 to 3.54)], excision not otherwise specified (NOS) (RR=2.02[1.60 to 2.55]), LLETZ (RR=1.56[1.36 to 1.79]), ablation NOS (RR=1.46[1.27 to 1.66]). The risk of PTB increased with repeat treatment (13.2 v 4.1%, RR=3.78[2.65 to 5.39]) and with increasing cone depth (≤12/10mm: 7.1 v 3.4%, RR=1.54[1.09 to 2.18]; ≥10/12mm: 9.8 v 3.4%, RR=1.93[1.62
kyrgiou M, Mitra A, Moscicki AB, 2016, Does the vaginal microbiota plays a role in the development of cervical cancer?, Translational Research, Vol: 179, Pages: 168-182, ISSN: 1931-5244
Persistent infection with oncogenic human papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer. The factors promoting persistence as well those triggering carcinogenetic pathways are incompletely understood. Rapidly evolving evidence indicates that the vaginal microbiome (VM) may play a functional role (both protective and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical cancer. The first studies examining the VM and the presence of an HPV infection using next-generation sequencing techniques identified higher microbial diversity in HPV-positive as opposed to HPV-negative women. Furthermore, there appears to be a temporal relationship between the VM and HPV infection in that specific community state types may be correlated with a higher chance of progression or regression of the infection. Studies describing the VM in women with preinvasive disease (squamous intraepithelial neoplasia [SIL]) consistently demonstrate a dysbiosis in women with the more severe disease. Although it is plausible that the composition of the VM may influence the host’s innate immune response, susceptibility to infection, and the development of cervical disease, the studies to date do not prove causality. Future studies should explore the causal link between the VM and the clinical outcome in longitudinal samples from existing biobanks.
Halliwell DE, Morais CLM, Lima KMG, et al., 2016, Imaging cervical cytology with scanning near-field optical microscopy (SNOM) coupled with an IR-FEL, Scientific Reports, Vol: 6, ISSN: 2045-2322
Cervical cancer remains a major cause of morbidity and mortality among women, especially in the developing world. Increased synthesis of proteins, lipids and nucleic acids is a pre-condition for the rapid proliferation of cancer cells. We show that scanning near-field optical microscopy, in combination with an infrared free electron laser (SNOM-IR-FEL), is able to distinguish between normal and squamous low-grade and high-grade dyskaryosis, and between normal and mixed squamous/glandular pre-invasive and adenocarcinoma cervical lesions, at designated wavelengths associated with DNA, Amide I/II and lipids. These findings evidence the promise of the SNOM-IR-FEL technique in obtaining chemical information relevant to the detection of cervical cell abnormalities and cancer diagnosis at spatial resolutions below the diffraction limit (≥0.2 μm). We compare these results with analyses following attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy; although this latter approach has been demonstrated to detect underlying cervical atypia missed by conventional cytology, it is limited by a spatial resolution of ~3 μm to 30 μm due to the optical diffraction limit.
Kyrgiou M, Mitra A, Paraskevaidis E, 2016, The Impact of Conservative Treatment for Cervical Intraepithelial Neoplasia and Early Cervical Cancer on Fertility and Early Pregnancy Outcomes, JAMA Oncology, ISSN: 2374-2445
Clinical Question: Does local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer adversely affect successful conception and early pregnancy outcomes in the first and second trimester (less than 24 weeks of gestation)?Clinical Application: Local cervical treatment does not adversely affect fertility or first trimester miscarriage, although it is associated with a significant increase in the risk of second trimester miscarriages.
Fotopoulou C, Jones BP, Savvatis K, et al., 2016, Maximal effort cytoreductive surgery for disseminated ovarian cancer in a UK setting: challenges and possibilities, Gynecologic Oncology, ISSN: 1095-6859
OBJECTIVE: To assess surgical morbidity and mortality of maximal effort cytoreductive surgery for disseminated epithelial ovarian cancer (EOC) in a UK tertiary center. METHODS/MATERIALS: A monocentric prospective analysis of surgical morbidity and mortality was performed for all consecutive EOC patients who underwent extensive cytoreductive surgery between 01/2013 and 12/2014. Surgical complexity was assessed by the Mayo clinic surgical complexity score (SCS). Only patients with high SCS ≥5 were included in the analysis. RESULTS: We evaluated 118 stage IIIC/IV patients, with a median age of 63 years (range 19-91); 47.5 % had ascites and 29 % a pleural effusion. Median duration of surgery was 247 min (range 100-540 min). Median surgical complexity score was 10 (range 5-15) consisting of bowel resection (71 %), stoma formation (13.6 %), diaphragmatic stripping/resection (67 %), liver/liver capsule resection (39 %), splenectomy (20 %), resection stomach/lesser sac (26.3 %), pleurectomy (17 %), coeliac trunk/subdiaphragmatic lymphadenectomy (8 %). Total macroscopic tumor clearance rate was 89 %. Major surgical complication rate was 18.6 % (n = 22), with a 28-day and 3-month mortality of 1.7 and 3.4 %, respectively. The anastomotic leak rate was 0.8 %; fistula/bowel perforation 3.4 %; thromboembolism 3.4 % and reoperation 4.2 %. Median intensive care unit and hospital stay were 1.7 (range 0-104) and 8 days (range 4-118), respectively. Four patients (3.3 %) failed to receive chemotherapy within the first 8 postoperative weeks. CONCLUSIONS: Maximal effort cytoreductive surgery for EOC is feasible within a UK setting with acceptable morbidity, low intestinal stoma rates and without clinically relevant delays to postoperative chemotherapy. Careful patient selection, and coordinated multidisciplinary effort appear to be the key for good outcome. Future ev
Kyrgiou M, Pouliakis A, Panayiotides JG, et al., 2016, Personalised management of women with cervical abnormalities using a clinical decision support scoring system, Gynecologic Oncology, Vol: 141, Pages: 29-35, ISSN: 1095-6859
OBJECTIVES: To develop a clinical decision support scoring system (DSSS) based on artificial neural networks (ANN) for personalised management of women with cervical abnormalities. METHODS: We recruited women with cervical abnormalities and healthy controls that attended for opportunistic screening between 2006 and 2014 in 3 University Hospitals. We prospectively collected detailed patient characteristics, the colposcopic impression and performed a series of biomarkers using a liquid-based cytology sample. These included HPV DNA typing, E6&E7 mRNA by NASBA or flow cytometry and p16INK4a immunostaining. We used ANNs to combine the cytology and biomarker results and develop a clinical DSSS with the aim to improve the diagnostic accuracy of tests and quantify the individual's risk for different histological diagnoses. We used histology as the gold standard. RESULTS: We analysed data from 2267 women that had complete or partial dataset of clinical and molecular data during their initial or followup visits (N=3565). Accuracy parameters (sensitivity, specificity, positive and negative predictive values) were assessed for the cytological result and/or HPV status and for the DSSS. The ANN predicted with higher accuracy the chances of high-grade (CIN2+), low grade (HPV/CIN1) and normal histology than cytology with or without HPV test. The sensitivity for prediction of CIN2 or worse was 93.0%, specificity 99.2% with high positive (93.3%) and negative (99.2%) predictive values. CONCLUSIONS: The DSSS based on an ANN of multilayer perceptron (MLP) type, can predict with the highest accuracy the histological diagnosis in women with abnormalities at cytology when compared with the use of tests alone. A user-friendly software based on this technology could be used to guide clinician decision making towards a more personalised care.
Kalliala I, Tsilidis K, Kyrgiou M, 2016, Obesity and gynaecological cancer - an umbrella review and meta-analysis, 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation, Publisher: SAGE Publications (UK and US), Pages: 179A-179A, ISSN: 1933-7205
Kyrgiou M, Athanasiou A, Paraskevadi M, et al., 2016, Risk of Preterm Birth After Treatment for Cervical Precancer Increases with Increasing Cone Depth: Systematic Review and Meta-Analysis., 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 189A-190A, ISSN: 1933-7191
Mitra A, Paraskevaidi M, Lai J, et al., 2016, Cervical Antimicrobial Peptides Are Decreased Following Excisional Treatment for Cervical Intraepithelial Neoplasia., 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 96A-97A, ISSN: 1933-7191
Mitra A, MacIntyre D, Lee Y, et al., 2016, Cervical Intraepithelial Neoplasia Disease Progression Is Associated with Increased Vaginal Microbiome Diversity., 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 66A-66A, ISSN: 1933-7191
Mitra A, Maclntyre D, Lee Y, et al., 2016, Characterisation of the vaginal microbiome in cervical intraepithelial neoplasia, Spring Meeting on Clinician Scientists in Training, Publisher: ELSEVIER SCIENCE INC, Pages: 75-75, ISSN: 0140-6736
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Farthing A, Kyrgiou M, 2016, Authors' Reply re: Laparoscopic radical abdominal trachelectomy for the management of stage IB1 cervical cancer at 14 weeks gestation: case report and review of the literature, BJOG: An International Journal of Obstetrics & Gynaecology, Vol: 123, Pages: 646-646, ISSN: 1470-0328
Sasieni P, Castanon A, Landy R, et al., 2015, Risk of preterm birth following surgical treatment for cervical disease: executive summary of a recent symposium, BJOG - An International Journal of Obstetrics and Gynaecology, Vol: 123, ISSN: 1470-0328
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