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Annular cervical detachment is a rare complication mostly associated with prolonged labour and the resultant vascular impairment. Although a remote possibility, such a complication is not unheard of with caesarean section. Here is one such case of annular detachment of cervix during caesarean section due to difficult delivery of fetus which was managed by repair of cut edges.

A woman in her mid-20s presented with bleeding at 18 weeks gestation from a cervical ‘polyp’. Histopathology demonstrated a rare small cell neuroendocrine of the cervix. There were only 18 cases of neuroendocrine tumours of the cervix in and around pregnancy in the literature, so the evidence base for treatment was scarce. She was treated with neoadjuvant chemotherapy, using a regimen used for small cell neuroendocrine tumours of the lung, to allow for fetal lung maturity. Disease initially responded, then progressed and she was delivered at 32 weeks by caesarean radical hysterectomy. Adjuvant treatment included further chemotherapy and radical pelvic radiotherapy. The woman and her child are doing well over 6 years after treatment, although the woman has significant side effects of both radical surgery and radiotherapy. This case emphasises the need for excellent communication between multidisciplinary professionals, patients and their families and using external colleagues to help with rare clinical problems.

Introduction Dapivirine (DPV), formulated as vaginal ring, demonstrated HIV risk reduction. MTN-026 explored DPV, formulated as rectal gel, for safety, pharmacokinetics, and acceptability. Methods HIV-uninfected men and women aged 18-45 years were enrolled at United States and Thailand sites and randomized 2:1 to receive DPV 0.05% or placebo gel via rectal applicator. A single dose phase was followed by 7 observed daily doses. Plasma, and fluid and tissue from both rectum and cervix were collected at baseline and after the final dose over 72 hours for pharmacokinetics, ex-vivo HIV-1 biopsy challenge, histology, and flow cytometry. Results 28 participants were randomized; 2 terminated early; 9 were female and 19 male; 12 were white, 11 Asian, 4 black and 1 other race/ethnicity. Mean age was 28.5 and 34.2 years in the DPV and placebo arms, respectively. Thirty adverse events occurred (all Grade 1 or 2, except one unrelated Grade 3) without study arm differences. DPV rectal tissue concentrations (median [interquartile range]) 0.5-1 and 2 hours after a single dose were 256 ng/gm (below limit of quantitation [BLQ], 666) and BLQ (BLQ, 600), respectively, then BLQ (BLQ, BLQ) from 24-72 hours; concentrations following multiple doses were similar. The largest median DPV plasma concentrations were 0.33 ng/mL (0.15, 0.48) after one dose and 0.40 (0.33, 0.49) after seven doses. Conclusions The DPV rectal gel was acceptable and without safety concerns. While DPV plasma concentrations were similar to the vaginal ring, rectal tissue concentrations were well below vaginal ring tissue concentrations, suggesting need for reformulation.

BACKGROUND: Venous varicosities are a relatively common finding during pregnancy. Rarely, varices can arise in the cervix and cause life-threatening maternal hemorrhage. This article offers an example of a patient who was diagnosed with bleeding cervical varices during pregnancy and summarizes the diagnosis and treatment strategies for the 20 other reported cases in the literature. METHODS: A PubMed literature search using the following terms was performed to gather data for the literature review: “bleeding” or “hemorrhage” and “cervical varices” or “cervical varix” or “cervical varicosities” and “pregnancy” or “obstetric” or “maternal.” Individual references cited in each article were also evaluated for inclusion in this review. RESULTS: A 50-year-old gravida 7 para 1 presented at 12 4/7 weeks with vaginal bleeding. Endo-vaginal ultrasound showed enhanced color Doppler signal in the endocervical canal. During a speculum exam, she was found to have active bleeding from ruptured cervical varicosities and required blood and fresh frozen plasma transfusion. Hemostasis was achieved with interrupted suture ligation. A McDonald cerclage was subsequently placed. She continued pregnant until delivery via cesarean section at 37 2/7 weeks. To date, there have only been 20 other reported cases of bleeding cervical varices during pregnancy. CONCLUSIONS: This case report and review of the literature highlight the importance of including bleeding cervical varices in the differential diagnosis of maternal hemorrhage and offer a treatment strategy if cervical varicosities are discovered during pregnancy.

Objective Our objective is to develop a site-specific proteomic-based screening test for ovarian cancer(OC) using the mucus of the cervix and vagina and evaluate a potential means for home testing. Methods Cervicovaginal fluid samples were obtained from ovarian cancer and normal control patients for LC-mass spectrometry(MS) proteomic evaluation. Statistical modeling determined the protein panel with the highest penetrance across ovarian cancer samples. A subcohort of patients consented to provide self-collected vaginal samples at home with questionnaire on feasibility. Cohen's kappa methodology was utilized to determine agreement between physician-collected and patient-collected samples. Results A total of 83 consecutive patient samples were collected prospectively (33 ovarian cancer & 50 controls). Thirty patients consented for self-collection. Using LC-MS, 30 peptides demonstrated independent statistical significance for detecting ovarian cancer. Using statistical modeling, the protein panel that determined the best predictor for detecting OC formed a “fingerprint” consisting of 5 proteins: s erine proteinase inhibitor A1; periplakin; profilin1; apolipoprotein A1; and thymosin beta4-like protein. These peptides demonstrated a significant increase probability of detecting ovarian cancer with the ROC curve having an AUC of 0.86 (p = 0.00001). Physician-collected and patient-collected specimens demonstrated moderate agreement with kappa average of 0.6 with upper bound of 0.75. Conclusions Using novel site-specific collection methods, we identified an OC “fingerprint” with adequate sensitivity and specificity to warrant further evaluation in a larger cohort. Agreement of physician-collected and patient-collected samples were encouraging and could improve access to screening with a home self-collection if this screening test is validated in future studies.

Objectives Anal squamous cell carcinoma (ASCC) has a higher incidence described in certain groups, namely, in women with vulvar high-grade squamous intraepithelial lesions (vHSILs) and/or human papillomavirus squamous cell carcinoma (VSCC). This review describes terminology, vHSIL, and VSCC in their association with ASCC and the published recommendations for early detection of this cancer in these women. Materials and methods A narrative review was conducted by the authors on vHSIL and VSCC as risk factors for ASCC. Results The ASCC and VSCC incidence are increasing. Women with vHSIL and/or VSCC can present with ASCC at diagnosis, being one of the highest-risk groups. Suspicious symptoms include rectal bleeding, pain, and a sensation of an anal mass. Digital anorectal examination can help detect early ASCC. Sensitivity of anal cytology in women with vHSIL and VSCC seems low, with the exception of immunosuppressed women with genital neoplasia (cervix, vagina, and vulva). There are still insufficient data on high-resolution anoscopy in women with vHSIL and/or VSCC as a screening method. Conclusions Clinicians need be aware that women with vHSIL and VSCC comprise one of the highest-risk groups for ASCC. Inquiring suggestive symptoms of ASCC and a digital anorectal examination can help in the early detection of this type of cancer.

Ureaplasma parvum is a commensal bacterium in the female reproductive tract but has been associated with pregnancy complications such as preterm prelabor rupture of membranes and preterm birth (PTB). However, the pathologic effects of U. parvum in the cervix, which prevents ascending infections during pregnancy, are still poorly understood. To determine the impact of U. parvum on the cervix, ectocervical (ecto) and endocervical (endo) epithelial and stromal cells were incubated with U. parvum. Macrophages were also tested as a proxy for cervical macrophages to determine the antigenicity of U. parvum. The effects of U. parvum, including influence on cell cycle and cell death, antimicrobial peptide (AMP) production, epithelial-to-mesenchymal transition (EMT), and inflammatory cytokine levels, were assessed. U. parvum colonized cervical epithelial and stromal cells 4 h post-infection. Like uninfected control, U. parvum neither inhibited cell cycle progression and nor caused cell death in cervical epithelial and stromal cells. U. parvum increased the production of the AMPs cathelicidin and human β-defensin 3 and exhibited weak signs of EMT evidenced by decreased cytokeratin 18 and increased vimentin expression in cervical epithelial cells. U. parvum induced a proinflammatory environment (cytokines) and increased MMP-9 in cervical epithelial cells but promoted pro- and anti-inflammatory response in cervical stromal cells and macrophages. U. parvum may colonize the cervical epithelial layer, but induction of AMPs and anti-inflammatory response may protect the cervix and may prevent ascending infections that can cause PTB. These findings suggest that U. parvum is a weak inducer of inflammation in the cervix.

PurposeTo test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer.Methods and materialsIn an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS.ResultsIn total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P=.048) and in the combined cohort (13% vs 35%, χ2P=.01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P=.216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group.ConclusionsPET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.

Background Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. Methods We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology. Results In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15–24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+. Conclusions Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

Pelvic organ prolapse and carcinoma of the cervix are common entities but their association is rare. In more than 60% of the cases, the uterine prolapse is present for at least 10 years.[1][1] The displacement of the uterine cervix from the natural environment of the vagina is thought to explain a

Implementation of quality control measures ensures acceptable performance by a laboratory. This study aims to assess the quality of cervical cytopathology reporting using quality metrics like atypical squamous cells (which include both atypical squamous cells of undetermined significance and atypical squamous cell -cannot rule out high grade squamous intraepithelial lesion)/squamous intraepithelial lesion (ASC/SIL), cytohistological correlation (CHC) and positive predictive value (PPV) of Papanicolaou (Pap) smears for squamous lesions of cervix.A retrospective study of Pap smears from 2015 to 2020 was performed. The quality metrics analysed include diagnoses of ASCUS, ASC-H and ASCUS/SIL ratio, CHC and PPV. Cases with cervical biopsies/hysterectomy were included for CHC, and discrepancy was defined as discordance in diagnostic category between cytology and histology in the CHC.A total of 22,695 cervical cytology smears were reported. Unsatisfactory smears (n = 290) were excluded. Squamous lesions were reported in 233 smears, and the Bethesda system of nomenclature was followed. A definitive diagnosis (SILs and SCC) was given in 74% of cases. ASCUS and ASC-H were reported in 47 and 14 cases, respectively. The most common lesion on Pap smear was high-grade squamous intraepithelial lesion (HSIL; n = 92), followed by low-grade squamous intraepithelial lesion (LSIL; n = 64), and two were ungradable SIL. Squamous cell carcinoma (SCC) was reported in 14 smears. The ASC/SIL ratio was 0.38. CHC (n = 139) was 100% for ASC-H, LSIL, SCC and 84.7% for HSIL. A review of discrepant cases suggested sampling and interpretational discrepancy in five and one cases, respectively. The PPV of Pap smear for squamous lesions was 96.4%.It is essential to have good quality cytopathology reports for early identification, which enables appropriate management. The most commonly used quality indicator for cytopathology is the ASCUS/SIL ratio. This study suggests the inclusion of the CHC and PPV values as quality metrics for Pap smear, since these are easily measurable and serve as a good indicator of quality in cervical cytopathology reporting.

Background Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP). Methods In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model. Results During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028). Conclusions The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

Cervical stenosis is a postoperative complication of conization for uterine cervical malignancy, but a standard method of preventing this complication has yet to be established. Collagen vitrigel is a collagen-based biomaterial that has antifibrotic and epithelization promoting actions. We evaluated the antistenotic effect of an indwelling collagen vitrigel membrane-coated nylon line (CVNL) after cervical conization in rabbits. In one group of rabbits, a CVNL was placed in the cervical canal after conization. In another group, a nylon line without a collagen coating was placed in the cervical canal after conization. The control group underwent cervical conization without placement of a device. The control (conization alone) and nylon (conization plus indwelling nylon line) groups exhibited cervical swelling. Rabbits in the CVNL group (cervical conization plus indwelling CVNL in the xerogel state) had a normal cervical surface. The cervical canal in the control group was enlarged and showed cystic changes attributed to cervical stenosis. The nylon group exhibited a trend toward cervical canal dilatation. In the CVNL group, the cervical canal was normal and did not show cystic dilatation. Fibrosis occurred to a lesser degree in the nylon group than in the control group, and the CVNL group exhibited minimal interstitial fibrosis. The control and nylon groups showed increased numbers of myofibroblasts in the regenerated cervix, but few myofibroblasts were observed in the CVNL group. Abundant collagen type III was observed in regenerated cervical tissue in the control and nylon groups but not in the CVNL group. The number of proliferative mesenchymal cells in the regenerated cervix was lowest in the CVNL group. The expressions of connective tissue growth factor (CTGF, a regulator of fibroblast growth and extracellular matrix secretion), extracellular signal-regulated protein kinases 1 and 2, and c-Jun N-terminal kinase (which are involved in the induction of CTGF by transforming growth factor-β) were lower in the CVNL group than in the control or nylon groups. This study describes an indwelling CVNL that prevents cervical stenosis and cystic changes after conization. These effects were likely mediated by inhibition of fibrosis, myofibroblast emergence, CTGF expression, and collagen type III deposition in regenerating cervix. Impact statement Collagen vitrigel is a high-density collagen material that promotes epithelization, inhibits fibrosis, and suppresses inflammation in regenerating tissue. We evaluated whether a collagen vitrigel membrane-coated nylon line would prevent cervical stenosis after conization in the rabbit. We found that an indwelling collagen vitrigel membrane-coated nylon line prevented cervical canal stenosis and cystic changes after cervical conization by inhibiting fibrosis, myofibroblast emergence, connective tissue growth factor expression, and collagen type III deposition in the regenerating cervix. Our device has potential as a new method of preventing cervical canal fibrosis and stenosis after conization for cervical cancer.

PURPOSE We assessed the impact of mHealth on Pap test screening uptake and also determined the factors that affect screening uptake among women in Lagos, Nigeria. MATERIALS AND METHODS A randomized controlled trial was carried out among women in two tertiary health institutions in Lagos, Nigeria, between July 2020 and March 2021. Participants were randomly assigned to either a text message (mHealth) intervention or usual care arm. The main study outcome was the uptake of Pap smear testing within 6 months of enrollment in the study. We tested the associations between two groups of continuous variables using the unpooled independent-sample t-test (normal distribution) and that of two groups of categorical variables with the chi-square (χ2) test. Using a multinomial logistic regression model, we adjusted for relevant sociodemographic and clinical predictors of uptake of Pap smear screening. Statistical significance was defined as P < .05. RESULTS There was a significantly higher rate of uptake of Pap smear screening among women in the mHealth arm compared with those in the usual care arm (51.0% v 35.7%, P = .031). Following adjustment in the final multivariate model, level of income (odds ratio [OR] = 5.13, 95% CI, 1.55 to 16.95), awareness of Pap smear (OR = 16.26; 95% CI, 2.49 to 76.64), General Outpatient clinic attendance, and introduction of mHealth intervention during follow-up (OR = 4.36; 95% CI, 1.44 to 13.22) were the independent predictors of Pap smear uptake. CONCLUSION The use of mHealth technologies intervention via short-text message services is a feasible solution for cervical cancer prevention in low- and middle-income countries, and thus, the widespread use of mHealth services by health care providers and policymakers could contribute to the implementation of cervical cancer prevention services in Nigeria and in the settings of other low- and middle-income countries.

Cancer incidence is rising in low- and especially middle-income countries (MIC), driven primarily by four high-burden cancers (breast, cervix, lung, colorectal). By 2030, more than two-thirds of all cancer deaths will occur in MICs. Prevention and early detection are required alongside efforts to improve access to cancer treatment. Successful strategies for decreasing cancer mortality in high-income countries are not always effective, feasible or affordable in other countries. In this review, we evaluate strategies for prevention and early detection of breast, cervix, lung, and colorectal cancers, focusing on modifiable risk factors and high-risk subpopulations. Tobacco taxation, human papilloma virus vaccination, cervical cancer screen-and-treat strategies, and efforts to reduce patient and health system–related delays in the early detection of breast and colorectal cancer represent the highest yield strategies for advancing cancer control in many MICs. An initial focus on high-risk populations is appropriate, with increasing population coverage as resources allow. These strategies can deliver significant cancer mortality gains, and serve as a foundation from which countries can develop comprehensive cancer control programs. Investment in national cancer surveillance infrastructure is needed; the absence of national cancer data to identify at-risk groups remains a barrier to the development of context-specific cancer control strategies.

Declining cervical cancer rates in the United States highlights the value of prevention and early detection of premalignant cervical disease afforded by the human papillomavirus vaccine and Pap smear. The availability of in-office loop electrosurgical excision procedure affords clinicians with a cost-effective and preferred tool for the excision of high-grade lesions of the cervix with minimal risk for severe adverse outcomes. The most recent American Society for Colposcopy and Cervical Pathology guidelines recommend a risk-based approach for the detection, treatment, and surveillance of cervical disease and specifically focus on the risk of developing cervical intraepithelial neoplasia 3 or worse histology.

Background Healthcare systems have adopted different strategies to reduce the burden of cervical cancer. In Poland, a population-based screening program was implemented in 2006, leading to a downward trend in cervical cancer burden. However, screening rates are still low in relation to other EU member states. In Poland, Pap smears are mainly performed by gynecologists rather than Primary Health Care (PHC) physicians. Little is known about the experiences and attitudes of the latter regarding cervical cancer screening in a PHC setting. Methods A cross-sectional questionnaire-based survey was carried out among 43 PHC physicians from the Malopolska region in Poland. Barriers and attitudes towards cytology in a PHC setting were evaluated. Results Approximately 35% of surveyed physicians reported having experience in performing cytology. Almost 75% of PHC physicians lacked the necessary equipment in their office to perform the screening. None of the studied physicians performed Pap smears in their office at the time. The reasons included: shortage of competence (78.57%) and time (69.05%), the perception of Pap smears as a task for gynecologists (69.05%), the lack of financial incentives (61.90%), and the belief that their patients would be unwilling to undergo the test in their PHC physician’s office (33.33%). More than three quarters (76.74%) declared they would be ready to perform Pap smears if the tests were additionally paid. No significant associations between PHC physicians’ characteristics and their willingness to perform cytology screening were found. Conclusion The primary barrier to perform Pap smears by PHC physicians does not lie in their personal reluctance but in the organization of the healthcare system. Provision of required training and proper funding allocation can likely improve the screening rate of cervical cancer in Poland.

OBJECTIVE To assess the cost-effectiveness of vaginal misoprostol (PGE1; 25 μg) compared with a slow-release dinoprostone (PGE2) pessary (10 μg) for labor induction due to an unfavorable cervix at term. METHODS We used data from an open-label multicenter, randomized non-inferiority trial that recruited women for whom labor was induced for medical reasons. The incremental cost-effectiveness ratio was assessed from the payer's perspective, with the focus on inpatient care costs and using the cesarean deliveries avoided (CDA) rate as the primary analysis and the rate of vaginal delivery within 24 h (VD24) as the secondary analysis. RESULTS Analyses were based on 790 women in each group. Differences between treatment arms were the mean cost per patient of €4410 and €4399, a CDA rate of 80.1% and 77.9% and a VD24 rate of 46.1% and 59.4% for dinoprostone and misoprostol, respectively. Dinoprostone is not cost-effective according to the CDA rate and misoprostol was either a cost-effective or a dominant strategy according to the VD24. CONCLUSION Misoprostol and dinoprostone have equal cost management with mixed efficacy according to the clinical outcome used. Finally, misoprostol may be an attractive option for hospitals as the price is lower and it is easier to use. TRIAL REGISTRATION ClinicalTrials.gov: NCT01765881. URL: https://clinicaltrials.gov/ct2/show/NCT01765881. ClinicalTrialRegistrer.eu: 2011-000933-35. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000933-35/FR.

Objective Sentinel lymph node (SLN) sampling in endometrial cancer staging has become an acceptable standard. Indocyanine green dye injected into the cervix and detected by near-infrared light is technically simple and sensitive. We aimed to evaluate SLN sampling in robot-assisted surgical staging of endometrial cancer at a university-affiliated teaching hospital. Methods A retrospective chart review, from January 2016 to December 2017, of patients who underwent robot-assisted surgical staging with cervical injection of indocyanine green dye detected by near-infrared light. The map rate, sensitivity, false negatives, and negative predictive value were calculated. Results A total of 105 charts were reviewed; 79 patients met inclusion criteria. The mean age was 65 (range 38-93) and the mean body mass index was 33.3 (range 16-49). Most patients (72.2%) had stage I disease and grade 1 or 2 histology (77.1%). Eight (10.1%) patients had lymph node metastasis. Seventy-two (91.1%) patients had positive mapping to at least 1 SLN. Sixty-two (78.5%) patients had bilateral mapping. Forty-four patients had concurrent pelvic ± para-aortic lymph node dissection and were included in the sensitivity analysis. Five of 44 cases had LN metastasis. The sensitivity was 80%, and the negative predictive value of SLN sampling was 97.5%. Conclusions SLN mapping and sampling at a university-affiliated teaching hospital have comparable map rate, sensitivity, and negative predictive value as demonstrated in multiple trials. The technique has the potential to standardize endometrial cancer staging across different practice settings.

NTRK1/2/3 rearrangements have been identified as oncogenic drivers in a variety of tumors including those in the uterine cervix, and rarely, the uterine corpus. We report 2 cases of cervical sarcoma with NTRK gene rearrangements. Case 1 was a 54-yr-old woman who presented with postmenopausal bleeding and a 5.4 cm friable mass in the cervix. Microscopic examination of the tumor revealed proliferation of epithelioid and spindle cells arranged in alternating hypercellular and hypocellular areas, with subtle fibrosarcoma-like features. Coagulative tumor cell necrosis and readily recognizable mitoses (up to 40 mitotic figures per 10 high-power fields) were identified. Case 2 was a 52-yr-old woman who presented with abnormal vaginal bleeding and a 1.3 cm cervical mass. The resected cervical tumor showed proliferation of spindled cells with fascicular and storiform growth pattern, infiltrating into the smooth muscle with entrapment of normal endocervical glands. The tumor cells displayed mild cytologic atypia and low mitotic activity (1 mitotic figure per 10 high-power fields). The mixed inflammatory infiltrate was seen throughout the lesion, mimicking morphology of inflammatory myofibroblastic tumor. Immunohistochemical staining for S100 and CD34 demonstrated variable expression in case 1 and uniformly diffuse positivity in case 2. The tumor cells in both cases were focally positive for CD10, Cyclin D1, ER, and PR, and negative for AE1/AE3, desmin, SOX10, HMB-45. RNA fusion analysis identified SPECC1L-NTRK3 gene rearrangements in case 1 and TPM3-NTRK1 in case 2; DNA-based mutational analysis also revealed CDKN2A/B homozygous deletion in case 1. Despite accumulating literatures on NTRK fusion mesenchymal tumors in gynecologic pathology, these tumors are still rare and lack well-established morphologic diagnostic criteria. Diagnostic and clinical recognition of these tumors is critical given the potential patient benefit from targeted therapy.

To compare the disease-free survival (DFS) and overall survival (OS) at 3 years and 5 years in patients undergoing treatment for early-stage cervical cancer with either robotic (RRH) or open radical hysterectomy (ORH). This retrospective study compared all patients with stage IA1 (lymphovascular invasion), IA2, IB1, IB2 and II A cervical cancer in accordance with International Federation of Gynaecology and Obstetrics staging (FIGO 2009) of cancer of the cervix uteri. Patients who underwent Radical Hysterectomy at our centre from January 2011 till January 2018 were included in the study. One hundred and eighty-nine patients ( ORH = 67, RRH = 122) were included. The median follow-up time was 46.3 months in RRH group and 70.0 months in the ORH group. The 3-year DFS was comparable in both the arms, 91.5% in RRH and 91.6% in ORH. The 5-year DFS was 88.9% and 85.9% in robotic and open approaches, respectively (P = 0.258), hazard ratio (HR) 0.616 (CI = 0.266-1.427). The 3-year overall survival for robotic approach was 93.4% and for open was 95%, whereas 5-year overall survival was 84.7% and 87.4% in robotic and open approaches, respectively (P = 0.813). The median estimated blood loss for robotics was lower (100 ml vs 300 ml, P

Objective: Adenocarcinoma in situ (AIS) of the cervix is a premalignant lesion, and a precursor of invasive disease. It is less frequent than its squamous counterpart. During pregnancy, AIS is a scarcely described scenario, whose diagnosis barely differs from non-pregnant patients. Its management is challenging with hysterectomy being the definitive treatment. However, its high incidence in young patients makes fertility-sparing management an approachable option for selected patients. The objective of this study is twofold. Firstly, we describe a case of a patient with AIS during pregnancy and the postpartum period. Secondly, the available literature is reviewed. Methods: Retrospective medical record review of a single case and a medical literature search in Pubmed of AIS cases in pregnant women. Results: A 31-year-old woman with cervical AIS diagnosed during pregnancy underwent serial fertility-sparing surgeries including a loop electrosurgical excision procedure and endocervical curettage during the second trimester, and a re-conization and a simple traquelectomy during the postpartum period, until negative margins were achieved. Upon reviewing the literature from 1965 to 2020, 23 other cases were found. Conclusion: Surgical management of cervical AIS during pregnancy is a safe procedure. Subsequent conservative surgeries imply a real challenge to preserve fertility. Sin financiación 4.447 JCR (2021) Q1, 17/85 Obtetrics & Ginecology 0.956 SJR (2021) Q1, 513/2489 Medicine (miscellaneous) No data IDR 2021 UEM

Despite aquaporin water channels (AQPs) play a critical role in maintaining water homeostasis in female reproductive tract and prompt a gradual increase in water content in cervical edema as pregnancy progressed, their relationship with macrophage infiltration and collagen content in human cervical remodeling need to be further investigated. This is the first study to examine the expression and localization of AQP3, AQP4, AQP5, AQP8, and macrophages simultaneously in human cervical ripening. The immunoreactivity of these AQPs was 2.6 to 6-fold higher on gestational weeks 26 (GD26W) than that on GD6W and GD15W, but AQP4 expression on GD39W dropped a similar extent on GD15W, other AQPs continued to rise on GD39W. The AQP3, AQP4, and AQP5 intensity seemed more abundant in cervical stroma than in the perivascular area on GD26W; the distribution of AQP3, AQP5, and AQP8 in cervical stroma was equivalent to that in the perivascular area on GD39W. Macrophage numbers were 1.7-fold higher in subepithelium region and 3.0-fold higher in center area on GD26W than that on GD15W; such numbers remained elevated on GD39W. The electron micrographs showed that cervical extensibility increased significantly on GD26W and GD39W accompanied with increased macrophage infiltration, cervical water content, and much more space among collagen fibers. These findings suggest that the upregulation of AQPs expression in human cervix is closely related to enhanced macrophage infiltration during pregnancy; there may be a positive feedback mechanism between them to lead the increase of water content and the degradation of collagen.

Aim In Japan, the criteria of the latent and active phases of the first stage of labor have not been decided. The Japan Society of Obstetrics and Gynecology (JSOG) Perinatal Committee conducted a study to construct a spontaneous labor curve in order to determine the point of onset of the active phase. Methods The participants were women who had spontaneous deliveries at four health facilities in Japan between September 1, 2011, and September 31, 2019. Spontaneous delivery was defined as the spontaneous onset of labor at term (37 weeks, 0 days to 41 weeks, 6 days) with vaginal delivery of a mature fetus in a cephalic position without uterotonic agents or epidural analgesia. The time points for each "cm" of dilation were collected starting from the time of full dilation retrogradely. The relationship between time since labor onset and cervical dilation was expressed as a curve using a smoothing B-spline. Results A total of 4215 primiparous and 5266 multiparous women were included in this study. The spontaneous labor curve showed that in both primiparous and multiparous women, labor progress was slow until 5 cm cervical dilation, accelerating between 5 and 6 cm dilation, and steadily progressed after 6 cm dilation. Conclusion We propose that the active phase of the first stage of labor be defined as starting at 5 cm dilation of the cervix, and that it be divided into an acceleration phase (5-6 cm dilation) and a maximal phase (>6 cm dilation).

Introduction Metastases to the female genital tract from extragenital primary tumors are unusual. We report a rare case of uterine cervix metastasis from colon adenocarcinoma and discuss diagnostic and therapeutic issues. Case report We report a case of a 38-year-old North African Caucasian woman treated for a non-metastatic colon adenocarcinoma. She had a sigmoidectomy and incomplete adjuvant chemotherapy. Six months later, she consulted with vaginal bleeding caused by a cervical tumor, which was confirmed to be metastatic disease, and the patient underwent decompressive and hemostatic radiotherapy. Conclusion Uterine cervix metastasis from primary colon adenocarcinoma is rare. The resection remains the standard protocol for the local treatment of resectable metastatic disease. Otherwise, systemic therapy is the preferable option.

A 27-year-old G1P1 patient diagnosed with a moderately differentiated squamous cell carcinoma of the cervix after cervical biopsy presented for counseling regarding fertility-sparing treatment immediately after diagnosis. The patient had no significant past medical history nor abdominal surgeries.

This review covers the significant new developments in the pathological classification of gynecological tumors. Many of these were included in the updated World Health Organization Classification of Female Genital Tract Tumours, published in 2020. Topics include the compelling evidence that a large majority of extrauterine high-grade serous carcinomas arise from the fallopian tube; the Cancer Genome Atlas (TCGA) Classification of endometrial carcinomas; the discovery that most so-called synchronous endometrial and ovarian endometrioid carcinomas represent metastasis from the endometrium to the ovary; and the division of cervical, vaginal, and vulval carcinomas into clinically meaningful HPV-associated and HPV-independent types. Newly described tumor types are covered, including endometrial and ovarian mesonephric-like adenocarcinoma, uterine sarcoma types associated with specific molecular abnormalities, and gastric (gastrointestinal)-type adenocarcinomas of the endometrium and vagina. Important molecular events in ovarian sex cord-stromal tumors are also discussed.

The cervix undergoes a dynamic remodeling process throughout pregnancy. Appropriate timing of cervical remodeling is essential in maintaining the fetus inside the uterus and ensuring cervical dilatation for safe delivery of the fetus at term. This study aims to determine the characteristics and trends of published articles in the field of cervical remodeling during pregnancy through a bibliometric analysis.A systematic review of the literature on cervical remodeling during pregnancy was performed on using the Scopus database from inception to 2020. The following information was obtained for each article: authors, year of publication, title, journal, institution, country, title, keywords, citation frequency, and relative citation ratio. The visualization of collaboration networks of countries and keywords related to cervical remodeling during pregnancy was conducted using VOSviewer software.A total of 1979 bibliographic records were obtained from Scopus database. The number of publications increased in the 1980s and peaked in 2010. A total of 80 countries produced research in cervical remodeling during pregnancy. The USA contributed the greatest number of publications (Our bibliometric analysis shows the trends and development, scientific impact, and collaboration in the field of cervical remodeling research. These results show the important discoveries in the past and provided new avenues for scientific and clinical investigations in the field.

Background: Biogenic amines (BAs) secreted by the sympathetic neural apparatus of rat uterus are reported to be conducive to the uterine functional activity during postpartum involution; the imbalance in BAs ratio could confer postpartum reproductive disorders including improper postpartum involution. Objective: The objective of this study is to identify the changes in the density of uterine sympathetic nerves implicated in the pathology of endometriosis, adenomyosis, and delayed uterine involution. The present study aims to ascertain ‘serotonin’ and ‘catecholamine’ concentrations in mesenteric mast cells (MCs), and structural elements of nerve fibers across the perivascular plexuses (PPs) and single sympathetic nerve terminals (SST). Methods: Furthermore, the density of their spatial distribution (SDP and SDT) in the uterine body, cervix, and mesometrium was determined during postpartum involution. Tissue specimens of postpartum uterus were obtained from 55 nulliparous female Wistar outbred strain rats, which were grouped according to the days after parturition at the time of sacrifice. The nerve fibers of PP and SST exhibited emerald green fluorescence, which was detected by glyoxylic acid fluorescence technique; the fluorescence invoked by BAs was identified by microspectrofluorimetry. Results: Concentrations of BAs were extensive in the varicosities of PP and SST on the 10th day. However, the highest BA concentrations were found in structural elements of PP in the uterine mesometrium in the initial days of postpartum. In mesenteric MC, serotonin and catecholamines were at the highest concentration on the 10th day of postpartum. Histamines peaked on the 6th day. Conclusion: SDP and SDT were increased significantly in all structural elements of uterine nerve fibers in the uterine body and cervix compared to SDP in mesentery. Considering that catecholamines and serotonin are antagonists in many aspects of their biological action, the ratio of BAs should be well-balanced to maintain anabolic- catabolic equilibrium in the rat uterus.

Purpose This provides a benchmark of dosimetric benefit and clinical cost of cone‐beam CT‐based online adaptive radiotherapy (ART) technology for cervical and rectal cancer patients. Methods An emulator of a CBCT‐based online ART system was used to simulate more than 300 treatments for 13 cervical and 15 rectal cancer patients. CBCT images were used to generate adaptive replans. To measure clinical resource cost, the six phases of the workflow were timed. To evaluate the dosimetric benefit, changes in dosimetric values were assessed. These included minimum dose (Dmin) and volume receiving 95% of prescription (V95%) for the planning target volume (PTV) and the clinical target volume (CTV), and maximum 2 cc's (D2cc) of the bladder, bowel, rectum, and sigmoid colon. Results The average duration of the workflow was 24.4 and 9.2 min for cervical and rectal cancer patients, respectively. A large proportion of time was dedicated to editing target contours (13.1 and 2.7 min, respectively). For cervical cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction 0.25 and 0.25 Gy, respectively. The replan changed the V95% by 9.2 and 7.9%. The D2cc to the bladder, bowel, rectum, and sigmoid colon for each fraction changed −0.02, −0.08, −0.07, and −0.04 Gy, respectively. For rectal cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction of 0.20 and 0.24 Gy, respectively. The replan changed the V95% by 4.1 and 1.5%. The D2cc to the bladder and bowel for each fraction changed 0.02 and −0.02 Gy, respectively. Conclusions Dosimetric benefits can be achieved with CBCT‐based online ART that is amenable to conventional appointment slots. The clinical significance of these benefits remains to be determined. Managing contours was the primary factor affecting the total duration and is imperative for safe and effective adaptive radiotherapy.

To investigate whether women with a short cervical length (CL), but delivered at term in the first pregnancy might have increased risks of having short cervix and spontaneous preterm birth (sPTB) in the subsequent pregnancies.This is a retrospective cohort study including singleton gestations who were delivered between Jan 2011 and Dec 2018, who had had one childbirth experience and who had transvaginal sonographic CL assessment performed at mid-trimester (18 ~ 30 weeks) in both pregnancy. The women were divided into four group according to the history of preterm birth and a short cervix ( 25 mm before 30 weeks of gestation): (1) the Preterm-short cervix group, (2) the Preterm-no shortening group, (3) the Term-short cervix group, and (4) the Term-no shortening group. We compared the risk of having short cervix and sPTB during the second pregnancy of women. Secondary outcomes were threatened preterm labor, need for tocolytics, and cerclage placement.A total of 804 women met our inclusion criteria. The rate of having short cervix ( 25 mm before 28 weeks of gestation) during the second pregnancy in women in the Term-short cervix group (43.2%) was significantly higher than those in women in the Term-no shortening group (6.6%), and in the Preterm-no shortening group (8.8%) (all p 0.001 with Bonferroni correction), but not higher than those in women with the Preterm-short cervix group (30.8%, p 0.05 with Bonferroni correction). When compared with women in the Preterm-no shortening group, women in the Term-short cervix group were also at an increased risk of need for need of tocolytics (60.2% vs. 26.5%) and cerclage placement (15.9% vs. 6.1%, all p 0.001). Women in the Term-short cervix group had an increased risk of sPTB ( 37 weeks) during the second pregnancy, as compared to those in the Term-no shortening group (adjusted odds ratio 5.098, 95% CI 2.107-11.874).Women with a history of short cervix in their first pregnancy, but who delivered at term, were at increased risk of having a short cervix and sPTB in their second pregnancy, as compared to women with a history of term delivery without cervical shortening. Thus, short cervix of the previous pregnancy might be a predictive factors for preterm birth in the subsequent pregnancy.

Purpose The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. Methods We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. Results We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12–2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67–4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81–10.26; deep 1/3, HR 7.05, CI 2.99–16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25–17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. Conclusions Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.

Background The aim of this study was to determine how Stathmin-1 and Heat Shock Protein 27 (HSP27) can be used as adjunctive biomarkers to differentiate high-grade dysplasia from benign/reactive lesions in cervical tissues. In addition, we aimed to see if any of these markers can differentiate endometrial from endocervical adenocarcinomas. Methods Fifty cases including benign cervical tissue, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ of the endocervix, invasive endocervical adenocarcinoma, and endometrial adenocarcinoma were selected. Stathmin-1 and HSP27 immunohistochemistry (IHC) were performed for each case and the results were compared to the previously available p16 IHC stains. Results p16 stained positively in 100% of HSIL, endocervical adenocarcinoma in situ, and invasive endocervical cases. Stathmin-1 stained positively in 43% of HSIL and 90% of endocervical adenocarcinoma in situ and all invasive endocervical cases. Stathmin-1 and p16 were negative in all benign cervical samples. Stathmin-1, HSP27, and p16 stained 100% of LSIL cases. HSP27 stained indiscriminately, including 100% of benign cervical tissue. 87% of the endometrial adenocarcinomas stained positively for p16, Stathmin-1, and HSP27. Conclusion p16 remains superior to both Stathmin-1 and HSP27 in differentiating dysplasia from benign, reactive changes of the cervix.

Background Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC. Methods This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen. Results Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24–83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p Conclusion Our results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies.

Preterm birth is the leading cause of neonatal morbidity and mortality. Spontaneous Preterm Birth (sPTB) has many and varied causes but is known to be strongly associated with a short or shortening cervix in the midtrimester of pregnancy. The strongest risk factor for sPTB is a previous sPTB. In women with a history of sPTB, we can offer surveillance and treatments which have been proven to reduce the risk of sPTB, such as cervical cerclage and vaginal progesterone supplementation. Alongside other indications, we currently use 25 mm or shorter as a "trigger threshold" for offering cervical cerclage treatment in the Preterm Birth Prevention Clinic at The National Maternity Hospital.To determine if using gestation-specific centiles instead of a 25 mm cut-off for cervical length changes the antenatal management of women at high risk of sPTB.This was a retrospective chart review of all women attending the preterm birth clinic over the 2-year period 2018-2020 in a large tertiary referral unit in Dublin, Ireland. Demographic details, obstetric history, preterm birth risk factors and preventative treatments offered were collected and analysed. Cervical lengths were measured with ultrasound using a standardised protocol and all performed or supervised by 2 experienced sonographers.A total of 200 patients with known risk factors for sPTB attended the Preterm Birth Surveillance Clinic at the National Maternity Hospital during the study period. Of these, 36/200 (18%) went on to deliver again prior to 37 weeks despite attending the clinic +/- receiving interventionsthis group are the focus of this paper. The indications for surveillance in this group that had a recurrent sPTB included recurrent second-trimester pregnancy losses/preterm delivery 34 weeks (26/36 (72%)), cervical trauma (including treatment of CIN) (12/36 (33%)), congenital abnormalities (1/36 (2.8%)), uterine anomaly (1/36 (2.8%)) and placental bleeding (1/36 (2.8%)). There was one smoker in this series. Funnelling was observed in 3/36 cases (8.3%). Of the 36 patients, an additional 15 would have received a cerclage had gestation-specific centiles, i.e.,5th centile, been used and an additional 10/36 (28%) would have been offered progesterone therapy.In those at high risk of preterm birth, the use of gestation-specific centiles for cervical length increases the proportion of patients that would be eligible for cervical cerclage. It is unclear whether this would change clinical outcome.

BACKGROUND/AIM Although still controversial, the current treatment for locally advanced neuroendocrine carcinoma of the cervix (NECC) relies on chemoradiation (CRT). The aim of this study is to evaluate the alternative role of combined chemotherapy and surgery in treating NECC. PATIENTS AND METHODS This is a retrospective series of patients undergoing radical surgery after neoadjuvant chemotherapy (NACT) for locally advanced NECC (stages IIB-IVA). Histological examination and immunohistochemistry were performed on surgical specimens to confirm diagnosis. Systematic literature search was conducted to identify other cases treated with chemotherapy and surgery. RESULTS Seven patients with a mean age of 49 years were identified. The mean greatest diameter at diagnosis was 59.3±24.7 mm. FIGO stage was IIB in 14.3% of patients, IIIB in 28.6%, IIIC in 42.9%, and IVA in 14.3%. The response to NACT was partial, ranging from 50% to 80%. Neuroendocrine markers were expressed in all cases. The mean progression-free survival (PFS) and overall survival (OS) were 15.0±30.6 months and 26.3±36.4 months, respectively. Eleven studies encompassing a total of 27 patients met eligibility criteria for the systematic review. CONCLUSION Surgery after NACT for locally advanced NECC may yield similar outcomes compared to CRT. The benefit of performing surgery as a primary approach could lie in the possibility of reserving CRT for recurrences. Since randomized clinical trials are difficult to be designed, an expert consensus is required to address the non-inferiority of radical surgery over CRT.