The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease.

Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.

Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis.

BACKGROUND: Incomplete excision of cervical precancer is associated with therapeutic failure and is therefore considered as a quality indicator of clinical practice. Conversely, the risk of preterm birth is reported to correlate with size of cervical excision and therefore balancing the risk of adequate treatment with iatrogenic harm is challenging. We reviewed the literature with an aim to reveal whether incomplete excision, reflected by presence of precancerous tissue at the section margins, or post-treatment HPV testing are accurate predictors of treatment failure. METHODS: We did a systematic review and meta-analysis to assess the risk of therapeutic failure associated with the histological status of the margins of the tissue excised to treat cervical precancer. We estimated the accuracy of the margin status to predict occurrence of residual or recurrent high-grade cervical intraepithelial neoplasia of grade two or worse (CIN2+) and compared it with post-treatment high-risk human papillomavirus (HPV) testing. We searched for published systematic reviews and new references from PubMed-MEDLINE, Embase, and CENTRAL and did also a new search spanning the period Jan 1, 1975, until Feb 1, 2016. Studies were eligible if women underwent treatment by excision of a histologically confirmed CIN2+ lesion, with verification of presence or absence of CIN at the resection margins; were tested by cytology or HPV assay between 3 months and 9 months after treatment; and had subsequent follow-up of at least 18 months post-treatment including histological confirmation of the occurrence of CIN2+. Primary endpoints were the proportion of positive section margins and the occurrence of treatment failure associated with the marginal status, in which treatment failure was defined as occurrence of residual or recurrent CIN2+. Information about positive resection margins and subsequent treatment failure was pooled using procedures for meta-analysis of binomial data and analysed using random-effects models. FINDINGS: 97 studies were eligible for inclusion in the meta-analysis and included 44 446 women treated for cervical precancer. The proportion of positive margins was 23·1% (95% CI 20·4-25·9) overall and varied by treatment procedure (ranging from 17·8% [12·9-23·2] for laser conisation to 25·9% [22·3-29·6] for large loop excision of the transformation zone) and increased by the severity of the treated lesion. The overall risk of residual or recurrent CIN2+ was 6·6% (95% CI 4·9-8·4) and was increased with positive compared with negative resection margins (relative risk 4·8, 95% CI 3·2-7·2). The pooled sensitivity and specificity to predict residual or recurrent CIN2+ was 55·8% (95% CI 45·8-65·5) and 84·4% (79·5-88·4), respectively, for the margin status, and 91·0% (82·3-95·5) and 83·8% (77·7-88·7), respectively, for high-risk HPV testing. A negative high-risk HPV test post treatment was associated with a risk of CIN2+ of 0·8%, whereas this risk was 3·7% when margins were free. INTERPRETATION: The risk of residual or recurrent CIN2+ is significantly greater with involved margins on excisional treatment; however, high-risk HPV post-treatment predicts treatment failure more accurately than margin status. FUNDING: European Federation for Colposcopy and Institut national du Cancer (INCA).

Trachelectomy during pregnancy: what has experience taught us?

The treatment of early stage cervical malignancy in a pregnant patient remains a challenge. We report the successful application of a vaginal radical trachelectomy (VRT) during pregnancy to treat a patient diagnosed with early stage cervical cancer and subsequently review the published work. A 22-year-old female diagnosed at the gestational age of 17 weeks with International Federation of Gynecology and Obstetrics stage IB1 squamous cell cervical carcinoma was treated with VRT at 19(+5) weeks. At 36 weeks, the patient underwent a scheduled cesarean section. A healthy male infant was delivered with a weight of 2795 g. After 13 months of follow-up, the patient is doing well with no evidence of recurrent disease.

The menstrual cycle and the COVID-19 pandemic.

BACKGROUND: The impact of COVID-19 virus on menstrual cycles in unvaccinated women is limited. OBJECTIVE: To investigate the prevalence of changes to menstrual cycle characteristics, hormonal symptoms and lifestyle changes prior to and during the COVID-19 pandemic. METHODS: A 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. RESULTS: 15,611 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 (P<0·001), bleeding duration more than seven days (P<0·001), longer mean cycle length (P<0·001) and overall bleeding duration (P<0·001). Over half the participants reported worsening of premenstrual symptoms including low mood/depression, anxiety and irritability. When stratified according to COVID-19 infection, there was no significant difference in menstrual cycle changes. CONCLUSION: The 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.

The association of in vitro fertilization/intracytoplasmic sperm injection results with anxiety levels and stress biomarkers: An observational, case-control study✰.

INTRODUCTION: Anxiety has been considered to exert a negative influence on fecundity. However, it remains unclear whether it is a cause or a consequence and whether it is associated with the treatment outcome. This observational case control study evaluated the levels of state anxiety and various stress biomarkers and assessed their association with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. MATERIALS AND METHODS: We allocated 109 infertile nulliparous women aged 25-45 years in their first IVF/ICSI fresh treatment cycle into two groups according to the final outcome: group A (PTP = pregnancy-test positive, n = 49) and group B (PTN = pregnancy-test negative, n = 60). State anxiety levels were measured with the Spielberger Trait Anxiety Inventory (STAI) questionnaire (Marteau and Bekker modification) on the days of oocyte retrieval (OR) and embryo transfer (ET). Serum stress biomarkers (cortisol, adrenaline, noradrenaline, α-amylase, and prolactin) were measured at the same time points. Blood samples were collected at 9 am. RESULTS: Most women in both groups showed comparable mild-to-moderate degrees of state anxiety on the days of OR and ET (p = 0.183 and p = 0.760, respectively). The stress biomarker measurements did not differ between the two groups, except for noradrenaline that was higher in group B (p = 0.015) and associated with significant cardiovascular changes. DISCUSSION: Women in both groups showed comparable levels of state anxiety, which were unlikely to influence the chance of pregnancy. Noradrenaline levels were higher in the non-pregnant group, with significant cardiovascular changes. Other stress biomarkers did not reflect the different treatment outcomes between the groups.

Laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) as a metabolomics platform in cervical cancer screening.

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.

Managing growing teratoma syndrome: new insights and clinical applications.

Although a recognized condition, growing teratoma syndrome (GTS) has no guidelines for management, and patients diagnosed with the condition are managed empirically by the most appropriate teams. We report a case of GTS in a 33-year-old patient who was initially treated with unilateral salpingo-oophorectomy and subsequent chemotherapy for a germ cell ovarian tumor. GTS was subsequently diagnosed with massive pelvic and upper abdominal masses as well as lung tumors. We also conducted a literature review on cases of GTS presenting with large tumors. Based on this, we suggest a management plan to guide the care of women with GTS. The condition is best managed in a multidisciplinary team involving the relevant surgeons, including gynecologist, abdominal and thoracic surgeons.

Genetic polymorphisms of matrix metalloproteinases 1-3 and their inhibitor are not associated with premature labor.

AIM: Extracellular matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are involved in the breakdown of fetal membranes before delivery. Our aim was to investigate the occurrence of any polymorphism on genes coding for MMPs 1-3 and TIMP 2 in preterm laboring patients as a potential source of this phenomenon. This question has not been studied before. METHODOLOGY & RESULTS: A prospective population study was performed in a Greek university hospital. Group A (control) included 66 women with no symptoms of premature labor. Group B (research) comprised 66 women, exhibiting signs of threatened preterm labor. No statistically significant difference in polymorphism, both in the distribution of genotype as well as allele frequencies, was detected between the two groups. This also applied to gestational age less or greater than 32 weeks. CONCLUSION: Gene polymorphisms of MMP 1-3 and TIMP 2 are not associated with premature rupture of membranes/contractions, as well as gestational age at preterm labor.

Fertility-sparing Surgery for Presumed Early-stage Invasive Cervical Cancer: A Survey of Practice in the United Kingdom.

AIM: To explore current practice in fertility-sparing surgery for cervical cancer in the UK. MATERIALS AND METHODS: A web-based structured questionnaire was designed and circulated to all members of the British Gynaecological Cancer Society. RESULTS: From 111 recipients, a total of 49 responses were collected. The majority of centres treated between 20-29 cases of invasive cervical cancer surgically (21/49, 42.9%) and performed between 0-5 cases of radical trachelectomy annually (29/49, 59.2%). The vaginal approach was the one most commonly used and was offered by almost half of the centres (21/49, 42.9%); laparoscopic techniques were offered in 13 (13/49, 26.6%). The responses were divided as to whether these cases should have been referred to supra-regional centres (25/49, 51.0%). CONCLUSION: With the use of Human Papillomavirus vaccination leading to a projected decrease in the number of cervical cancer incidence, patients may need to be referred to supraregional centres in the future.